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Sample records for photosensitization-induced early stages

  1. Staging Early Esophageal Cancer.

    PubMed

    Old, O J; Isabelle, M; Barr, H

    2016-01-01

    Staging esophageal cancer provides a standardized measure of the extent of disease that can be used to inform decisions about therapy and guide prognosis. For esophageal cancer, the treatment pathways vary greatly depending on stage of disease, and accurate staging is therefore crucial in ensuring the optimal therapy for each patient. For early esophageal cancer (T1 lesions), endoscopic resection can be curative and simultaneously gives accurate staging of depth of invasion. For tumors invading the submucosa or more advanced disease, comprehensive investigation is required to accurately stage the tumor and assess suitability for curative resection. A combined imaging approach of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) offers complementary diagnostic information and gives the greatest chance of accurate staging. Staging laparoscopy can identify peritoneal disease and small superficial liver lesions that could be missed on CT or PET, and alters management in up to 20 % of patients. Optical diagnostic techniques offer the prospect of further extending the possibilities of endoscopic staging in real time. Optical coherence tomography can image superficial lesions and could provide information on depth of invasion for these lesions. Real-time lymph node analysis using optical diagnostics such as Raman spectroscopy could be used to support immediate endoscopic therapy without waiting for results of cytology or further investigations. PMID:27573772

  2. Morphogenesis of early stage melanoma

    NASA Astrophysics Data System (ADS)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  3. Early stage of nanocrystal growth

    SciTech Connect

    2012-01-01

    Berkeley Lab researchers at the Molecular Foundry have elucidated important mechanisms behind oriented attachment, the phenomenon that drives biomineralization and the growth of nanocrystals. This electron microscopy movie shows the early stage of nanocrystal growth. Nanoparticles make transient contact at many points and orientations until their lattices are perfectly matched. The particles then make a sudden jump-to-contact to form attached aggregates. (Movie courtesy of Jim DeYoreo)

  4. Early stages of Ostwald ripening

    NASA Astrophysics Data System (ADS)

    Shneidman, Vitaly A.

    2013-07-01

    The Becker-Döring (BD) nucleation equation is known to predict a narrow double-exponential front (DEF) in the distribution of growing particles over sizes, which is due to early transient effects. When mass conservation is included, nucleation is eventually exhausted while independent growth is replaced by ripening. Despite the enormous difference in the associated time scales, and the resulting demand on numerics, within the generalized BD model the early DEF is shown to be crucial for the selection of the unique self-similar Lifshitz-Slyozov-Wagner asymptotic regime. Being preserved till the latest stages of growth, the DEF provides a universal part of the initial conditions for the ripening problem, regardless of the mass exchange mechanism between the nucleus and the matrix.

  5. 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.

  6. Endoscopic options for early stage esophageal cancer

    PubMed Central

    Shah, Pari M.

    2015-01-01

    Surgery has traditionally been the preferred treatment for early stage esophageal cancer. Recent advances in endoscopic treatments have been shown to be effective and safe. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) allow endoscopists to remove small, superficial lesions, providing tumor specimen that can be examined for accurate pathologic tumor staging and assessment of adequacy of resection. Endoscopic ablation procedures, including photodynamic therapy (PDT) and radio frequency ablation (RFA), have also been shown to safely and effectively treat esophageal dysplasia and early stage neoplasia, with excellent long-term disease control. Both approaches are becoming more widely available around the world, and provide an alternative, safe, low risk strategy for treating early stage disease, making combined endoscopic therapy the recommended treatment of choice for early stage esophageal cancers. PMID:25642334

  7. 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.

  8. The treatment of early stage ovarian cancer.

    PubMed

    Young, R C

    1995-10-01

    Approximately one third of women with ovarian cancer present with localized disease. A series of recent studies have identified a population of patients who require only comprehensive surgical staging for optimal results and another group that may benefit from adjuvant therapy. A series of national and international studies are evaluating a variety of adjuvant treatments in prospective randomized trials that may enhance long-term survival in poor-prognosis early ovarian cancer. PMID:7481865

  9. 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. PMID:27445872

  10. 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

  11. Early-Stage Breast Cancer Treatment Fact Sheet

    MedlinePlus

    ... breast cancer treatment fact sheet ePublications Early-stage breast cancer treatment fact sheet Print this fact sheet Early-stage breast cancer treatment fact sheet (PDF, 943 KB) Related information ...

  12. Urinary Biomarkers at Early ADPKD Disease Stage

    PubMed Central

    Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

    2015-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

  13. Complement Factor H Autoantibodies are Associated with Early Stage NSCLC

    PubMed Central

    Amornsiripanitch, Nita; Hong, Shaolin; Campa, Michael J.; Frank, Michael M.; Gottlin, Elizabeth B.; Patz, Edward F.

    2010-01-01

    Purpose In order to discover diagnostic biomarkers associated with early stage non-small cell lung cancer (NSCLC), we searched for autoantibodies preferentially present in stage I patients compared to patients with advanced stage disease. Here we describe an autoantibody against complement factor H (CFH) and its association with early stage NSCLC. Experimental Design Immunoblots were used to detect autoantibodies in the sera of stage I NSCLC patients. An autoantibody recognizing a 150 kDa protein was discovered and the protein was identified by mass spectrometry. The association of the autoantibody with early stage disease was suggested by the results of immunoblot analysis with sera from 28 stage I patients and 28 stage III/IV patients. This association was confirmed by protein microarray of sera from 125 NSCLC patients of all stages as well as 125 age, gender, and smoking history matched controls. Results The immunoreactive protein was identified as CFH. By immunoblot analysis, anti-CFH autoantibody was found in 50% of stage I NSCLC patients and 11% of late stage NSCLC patients (P=0.003). By protein microarray analysis, patients with stage I NSCLC had a significantly higher incidence of anti-CFH antibody than those with late stage NSCLC (P=0.0051). The percentage of sera with a positive level of CFH autoantibody was 30.4% in stage I, 21.1% in stage II, 12.5% in stage III, 7.4% in stage IV and 8.0% in the control group. Conclusions These findings suggest that in patients with NSCLC, CFH autoantibody is a molecular marker associated with early stage disease. PMID:20515868

  14. A First Language: The Early Stages.

    ERIC Educational Resources Information Center

    Brown, Roger

    This book focuses on the nature and development of knowledge concerning grammar and the meanings coded by grammar. This knowledge is inferred from performance, from sentences and the settings in which they are spoken, and from signs of comprehension or incomprehension of sentences by preschool children. The first two stages of linguistic…

  15. Discovering colorons at the early stage LHC

    SciTech Connect

    Dicus, Duane A.; Kao, Chung; Sayre, Joshua; Nandi, S.

    2011-05-01

    Prospects are investigated for the discovery of massive hypergluons using data from the early runs of the Large Hadron Collider. A center of mass energy of 7 TeV and an integrated luminosity of 1 fb{sup -1} or 5 fb{sup -1} are assumed. A phenomenological Lagrangian is adopted to evaluate the cross section of a pair of colored vector bosons (colorons, {rho}-tilde) decaying into four colored scalar resonances (hyperpions, {pi}-tilde), which then decay into eight gluons. The dominant eight-jet background from the production of 8g, 7g1q, 6g2q, and 5g3q is included. We find an abundance of signal events and that realistic cuts reduce the background enough to establish a 5{sigma} signal for the coloron mass of up to 733 GeV with 1 fb{sup -1} or 833 GeV with 5 fb{sup -1}.

  16. A Four Stage Approach to Early Childhood Intervention.

    ERIC Educational Resources Information Center

    Haber, Julian S.

    This paper describes a model for the involvement of primary health care personnel in the identification and treatment of developmental disabilities as a part of early childhood intervention programs. The integrated multidisciplinary model is divided into four stages. During the first stage an assignment of prenatal, perinatal, and postnatal risk…

  17. SEOM clinical guidelines in early-stage breast cancer 2015.

    PubMed

    Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

    2015-12-01

    Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

  18. Supportive seminar groups: an intervention for early stage dementia patients.

    PubMed

    Snyder, L; Quayhagen, M P; Shepherd, S; Bower, D

    1995-10-01

    A supportive seminar group was developed and conducted for individuals with early stage dementia and their caregivers. The eight sessions focused on pertinent topics, namely, coping with memory problems, daily living, self-esteem, relationships, health, legal, and financial concerns. Content analysis of the evaluative statements from nine men and six women patients revealed positive themes of feelings of purposefulness, gratification, belongingness, and survival, while other themes reflected the turmoil of the disease, namely, feelings of helplessness, devaluation, and unpredictability. These preliminary findings lend support to the feasibility of a group approach for early stage dementia patients.

  19. Early morphea simulating patch-stage mycosis fungoides.

    PubMed

    Fujimoto, Masakazu; Basko-Plluska, Juliana L; Petronic-Rosic, Vesna; Shea, Christopher R

    2015-05-01

    Morphea is a rare fibrosing condition of the skin and underlying tissues characterized histopathologically by thickened collagen bundles throughout the dermis, loss of adnexal structures, and "fat trapping." In the early stages of morphea, the absence of the fully developed characteristic findings may cause diagnostic confusion for the practicing pathologist. The authors report an unusual case of early morphea misdiagnosed as patch-stage poikilodermatous mycosis fungoides (MF) based on the initial clinical, histopathologic, and molecular findings. However, as time elapsed, well-developed lesions revealed clinical and histopathologic features diagnostic of morphea. The authors report this case to illustrate that lesions of early morphea may simulate MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret early morphea as MF.

  20. Radical Hysterectomy for Early Stage Cervical Cancer: Laparoscopy Versus Laparotomy

    PubMed Central

    McBee, William C.; Richard, Scott D.; Edwards, Robert P.

    2011-01-01

    Objectives: Gynecologic oncologists have recently begun using laparoscopic techniques to treat early stage cervical cancer. We evaluated a single institution's experience of laparoscopic radical hysterectomy and staging compared with laparotomy. Methods: A retrospective chart review identified stage IA2 and IB1 cervical cancer patients who underwent laparoscopic radical hysterectomy and pelvic lymph node dissection from July 2003 to April 2009. A 2:1 cohort of patients treated with laparotomy were matched by stage. Results: Nine laparoscopic patients (3 stage IA2, 6 stage IB1) with 18 matched controls (6 and 12) were identified. Demographics for each group were similar. None had positive margins or lymph nodes. An average of 11.2 vs.13.9 pelvic lymph nodes (P=0.237) were removed. Average operating time was 231.7 vs. 207.2 minutes (P=0.434), and average estimated blood loss was 161.1 vs. 394.4mL (P=0.059). Average length of stay was 2.9 vs. 5.5 days (P=0.012). No transfusions or operative complications were noted in the laparoscopic group vs. 3 each in the open group (P=0.194). No laparoscopic patients and 5 open patients had a postoperative wound infection (P=0.079). No recurrences were noted. Conclusions: Laparoscopic radical hysterectomy is a feasible alternative to laparotomy for early stage cervical cancer. Similar surgical outcomes are achieved with significantly less morbidity. PMID:21902978

  1. 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

  2. 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.

  3. 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...

  4. Genome-Based Risk Prediction for Early Stage Breast Cancer

    PubMed Central

    Adaniel, Christina; Jhaveri, Komal; Heguy, Adriana

    2014-01-01

    Tests to better characterize tumor genomic architecture are quickly becoming a standard of care in oncology. For breast cancer, the use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I–II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. In the last 5 years, more assays have become available to the practicing oncologist. Given the rapidity with which this field has evolved, it is prudent to review the tests, their indications, and the studies from which they have been validated. We present a comprehensive review of the available gene expression assays for early stage breast cancer. We review data for several individual tests and comparative studies looking at risk prediction and cost-effectiveness. PMID:25187476

  5. Surgical Treatment of Early-Stage Cervical Cancer.

    PubMed

    Brucker, Sara Y; Ulrich, Uwe A

    2016-01-01

    Surgical treatment of cervical cancer has been a cornerstone in the management of this malignancy for more than 100 years. Today, for early-stage and low-risk cervical cancer, surgery is still considered the gold standard. If the preoperative assessment of the tumor reveals a situation prompting postoperative adjuvant radiochemotherapy, the latter should be planned as the primary treatment option, being preceded by staging laparoscopy including pelvic and paraaortic lymph node dissection. As an alternative to the open approach, the definitive surgical treatment should be either performed laparoscopically, or be laparoscopic-assisted, or laparoscopically robotic-assisted. PMID:27614875

  6. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    PubMed Central

    Hong, Yu; Long, Jiang; Li, Hai; Chen, Shuhong; Liu, Qiqi; Zhang, Bei; He, Xiaomin; Wang, Yan; Li, Hongyi; Li, Yimei; Zhang, Tao; Lu, Chenzhen; Yan, Hao; Zhang, Minli; Li, Qing; Cao, Bangwei; Bai, Zhigang; Wang, Jin; Zhang, Zhongtao; Zhu, Shengtao; Zheng, Jiasheng; Ou, Xiaojuan; Ma, Hong; Jia, Jidong; You, Hong; Wang, Shengqi; Huang, Jian

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. Methods Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy. Findings Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum α-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60. Interpretation Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC. PMID:26137588

  7. 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.

  8. 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

  9. 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.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25788417

  11. 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.

  12. Motor-cortical oscillations in early stages of Parkinson's disease

    PubMed Central

    Pollok, B; Krause, V; Martsch, W; Wach, C; Schnitzler, A; Südmeyer, M

    2012-01-01

    Pathophysiological changes in basal ganglia-thalamo-cortical circuits are well established in idiopathic Parkinson's disease (PD). However, it remains open whether such alterations already occur at early stages representing a characteristic neurophysiological marker of PD. Therefore, the present study aims at elucidating changes of synchronised oscillatory activity in early PD patients. In this study, we performed whole-head magnetoencephalography (MEG) in a resting condition and during steady state contraction of the more severely affected forearm in 10 drug–naive, de novo patients, in 10 early-stage patients with chronic medication and in 10 age-matched control subjects. While cortico-muscular coherence (CMC) did not differ between groups, patients showed increased sensori-motor cortical power at beta frequency (13–30 Hz) during rest as well as during isometric contraction compared to controls. In healthy control subjects the power of the contralateral hemisphere was significantly suppressed during isometric contraction. By contrast, both hemispheres were activated equally strongly in de novo patients. In medicated patients, the pattern was found to be reversed. Contralateral beta power was significantly correlated with motor impairment during isometric contraction but not during rest. The present results suggest that the reduced ability of the primary motor cortex to disengage from increased beta band oscillations during the execution of movements is an early marker of PD. PMID:22547636

  13. Early stages in the development of stress corrosion cracks

    SciTech Connect

    Jones, R.H.; Simonen, E.P.

    1993-12-01

    Processes in growth of short cracks and stage I of long stress corrosion cracks were identified and evaluated. There is evidence that electrochemical effects can cause short stress corrosion cracks to grow at rates faster or slower than long cracks. Short cracks can grow at faster rates than long cracks for a salt film dissolution growth mechanism or from reduced oxygen inhibition of hydrolytic acidification. An increasing crack growth rate with increasing crack length could result from a process of increasing crack tip concentration of a critical anion, such as Cl{sup {minus}}, with increasing crack length in a system where the crack velocity is dependent on the Cl{sup {minus}} or some other anion concentration. An increasing potential drop between crack tip and mouth would result in an increased anion concentration at the crack tip and hence an increasing crack velocity. Stage I behavior of long cracks is another early development stage in the life of a stress corrosion crack which is poorly understood. This stage can be described by da/dt = AK{sup m} where da/dt is crack velocity, A is a constant, K is stress intensity and m ranges from 2 to 24 for a variety of materials and environments. Only the salt film dissolution model was found to quantitatively describe this stage; however, the model was only tested on one material and its general applicability is unknown.

  14. Point pressure sensitivity in early stage Parkinson's disease.

    PubMed

    Doty, Richard L; Gandhi, Shifa S; Osman, Allen; Hurtig, Howard I; Pawasarat, Ian; Beals, Evan; Chung, Inna; Dubroff, Jacob; Newberg, Andrew; Ying, Gui-Shang; Leon-Sarmiento, Fidias E

    2015-01-01

    A number of sensory changes occur in the earliest stages of Parkinson's disease (PD), some of which precede the expression of the classic motor phenotype by years (e.g., olfactory dysfunction). Whether point pressure sensitivity (PPS), a cutaneous measure of light touch mediated by myelinated Aβ fibers, is altered in early PD is not clear. Prior studies on this point are contradictory and are based on non-forced-choice threshold tests that confound the sensitivity measure with the response criterion. While α-synuclein pathology, a defining feature of PD, is present in the skin of PD patients, it is restricted to unmyelinated nerve fibers, suggesting PPS may be spared in this disease. We determined PPS thresholds using a state-of-the-art forced-choice staircase threshold test paradigm in 29 early stage PD patients and 29 matched controls at 11 body sites: the center of the forehead and the left and right forearms, index fingers, palms, medial soles of the feet, and plantar halluces. The patients were tested, in counterbalanced sessions, both on and off dopamine-related medications (DRMs). PPS was not influenced by PD and did not correlate with DRM l-DOPA equivalents, scores on the Unified Parkinson's Disease Rating Scale, side of the major motor disturbances, or SPECT imaging of the striatal dopamine transporter, as measured by technetium-99m TRODAT. However, PPS thresholds were lower on the left than on the right side of the body (p=0.008) and on the upper extremities relative to the toes and feet (ps<0.0001). Positive correlations were evident among the thresholds obtained across all body sectors, even though disparate regions of the body differed in terms of absolute sensitivity. This study indicates that PPS is not influenced in early stage PD regardless of whether patients are on or off DRMs. PMID:25447476

  15. Early stage of superradiance from Bose-Einstein condensates

    SciTech Connect

    Buchmann, L. F.; Lambropoulos, P.; Nikolopoulos, G. M.; Zobay, O.

    2010-08-15

    We investigate the dynamics of matter and optical waves at the early stage of superradiant Rayleigh scattering from Bose-Einstein condensates. Our analysis is within a spatially dependent quantum model which is capable of providing analytic solutions for the operators of interest. The predictions of the present model are compared to the predictions of a closely related mean-field model, and we provide a procedure that allows one to calculate quantum expectation values by averaging over semiclassical solutions. The coherence properties of the outgoing scattered light are also analyzed, and it is shown that the corresponding correlation functions may provide detailed information about the internal dynamics of the system.

  16. In vivo research using early life stage models.

    PubMed

    Seabra, Rita; Bhogal, Nirmala

    2010-01-01

    Scientists, for a variety of reasons, need to carry out in vivo research. Since experiments that require the use of adult animals pose various logistical, economical and ethical issues, the use of embryonic and larval forms of some organisms are potentially attractive alternatives. Early life stages are appealing because, in general, large numbers of individuals can be maintained in relatively simple housing, minimising costs, and their use involves fewer legal formalities. With this succinct review, we aim to provide an overview of different biological issues that have been successfully explored with the help of eggs, embryos and larvae from the frog, zebrafish and chicken.

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

    USGS Publications Warehouse

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

  18. Systemic immune system alterations in early stages of Alzheimer's disease.

    PubMed

    Zhang, Rongzhen; Miller, Robert G; Madison, Catherine; Jin, Xia; Honrada, Ronald; Harris, Will; Katz, Jonathan; Forshew, Dallas A; McGrath, Michael S

    2013-03-15

    Immune activation and inflammation play significant roles in the pathogenesis of Alzheimer's disease (AD). To test whether AD patients showed systemic manifestations of inflammation, blood from 41 patients with early stages of AD and 31 aged-match elderly controls were evaluated. Cellular markers for monocyte/macrophage (MO) activation and CD8 T lymphocyte were increased in early AD patients. Expression of monocyte CCR2, the receptor for monocyte chemoattractant protein-1 (MCP-1), was decreased; however, plasma MCP-1 levels were significantly increased and were related to the degree of MO activation in AD. These findings suggest that AD pathogenesis may be influenced by systemic immunologic dysfunction and provides potential immunologic targets for therapeutic intervention.

  19. 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.

  20. 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

  1. 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.

  2. A patient with medulloblastoma in its early developmental stage.

    PubMed

    Shinojima, Naoki; Nakamura, Hideo; Tasaki, Masayoshi; Kameno, Kouki; Anai, Shigeo; Iyama, Ken-ichi; Ando, Yukio; Seto, Hiroshi; Kuratsu, Jun-Ichi

    2014-12-01

    Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

  3. An Early-Stage Atherosclerosis Research Model Based on Microfluidics.

    PubMed

    Zheng, Wenfu; Huang, Rong; Jiang, Bo; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

    2016-04-01

    The arterial microenvironment plays a vital role in the pathology of atherosclerosis (AS). However, the interplay between the arterial microenvironment and atherogenesis remains unclear, partially due to the gap between cell culture and animal experiments. Addressing this problem, the present study reports a microfluidic AS model reconstituting early-stage AS. Physiological or AS-prone hemodynamic conditions are recapitulated on the model. The on-chip model recaptures the atherogenic responses of endothelial cells (ECs) in ways that the Petri dish could not. Significant cytotoxicity of a clinical anti-atherosclerotic drug probucol is discovered on the model, which does not appear on Petri dish but is supported by previous clinical evidence. Moreover, the anti-AS efficiency of platinum-nanoparticles (Pt-NPs) on the model shows excellent consistency with animal experiments. The early-stage AS model shows an excellent connection between Petri dish and animal experiments and highlights its promising role in bridging fundamental AS research, drug screening, and clinical trials. PMID:26890624

  4. 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.

  5. Adjuvant platinum-based chemotherapy for early stage cervical cancer

    PubMed Central

    Rosa, Daniela D; Medeiros, Lídia RF; Edelweiss, Maria I; Pohlmann, Paula R; Stein, Airton T

    2014-01-01

    Background This is an updated version of the original Cochrane review published in The Cochrane Library 2009, Issue 3. Most women with early cervical cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We performed this review originally because it was unclear whether cisplatin-based chemotherapy after surgery, radiotherapy or both, in women with early stage disease with risk factors for recurrence, was associated with additional survival benefits or risks. Objectives To evaluate the effectiveness and safety of platinum-based chemotherapy after radical hysterectomy, radiotherapy, or both in the treatment of early stage cervical cancer. Search methods For the original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, BIOLOGICAL ABSTRACTS and CancerLit, the National Research Register and Clinical Trials register, with no language restriction. We handsearched abstracts of scientific meetings and other relevant publications. We extended the database searches to November 2011 for this update. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at least one risk factor for recurrence. Data collection and analysis Two review authors extracted data independently. Meta-analysis was performed using a random-effects model, with death and disease progression as outcomes. Main results For this updated version, we identified three additional ongoing trials but no new studies for inclusion. Three trials including 368 evaluable women with early cervical cancer were included in the meta-analyses. The median follow-up period in these trials ranged from 29 to 42 months. All women had undergone surgery first. Two trials

  6. Metamorphic density controls on early-stage subduction dynamics

    NASA Astrophysics Data System (ADS)

    Duesterhoeft, Erik; Oberhänsli, Roland; Bousquet, Romain

    2013-04-01

    Subduction is primarily driven by the densification of the downgoing oceanic slab, due to dynamic P-T-fields in subduction zones. It is crucial to unravel slab densification induced by metamorphic reactions to understand the influence on plate dynamics. By analyzing the density and metamorphic structure of subduction zones, we may gain knowledge about the driving, metamorphic processes in a subduction zone like the eclogitization (i.e., the transformation of a MORB to an eclogite), the breakdown of hydrous minerals and the release of fluid or the generation of partial melts. We have therefore developed a 2D subduction zone model down to 250 km that is based on thermodynamic equilibrium assemblage computations. Our model computes the "metamorphic density" of rocks as a function of pressure, temperature and chemical composition using the Theriak-Domino software package at different time stages. We have used this model to investigate how the hydration, dehydration, partial melting and fractionation processes of rocks all influence the metamorphic density and greatly depend on the temperature field within subduction systems. These processes are commonly neglected by other approaches (e.g., gravitational or thermomechanical in nature) reproducing the density distribution within this tectonic setting. The process of eclogitization is assumed as being important to subduction dynamics, based on the very high density (3.6 g/cm3) of eclogitic rocks. The eclogitization in a MORB-type crust is possible only if the rock reaches the garnet phase stability field. This process is primarily temperature driven. Our model demonstrates that the initiation of eclogitization of the slab is not the only significant process that makes the descending slab denser and is responsible for the slab pull force. Indeed, our results show that the densification of the downgoing lithospheric mantle (due to an increase of pressure) starts in the early subduction stage and makes a significant

  7. 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.

  8. Early Stage Relapsing Polychondritis Diagnosed by Nasal Septum Biopsy

    PubMed Central

    Kobayashi, Takaaki; Moody, Sandra; Komori, Masafumi; Jibatake, Akira; Yaegashi, Makito

    2015-01-01

    Relapsing polychondritis is a rare inflammation of cartilaginous tissues, the diagnosis of which is usually delayed by a mean period of 2.9 years from symptom onset. We present the case of a 36-year-old man with nasal pain and fever. Physical examination of the nose was grossly unremarkable, but there was significant tenderness of the nasal bridge. Acute sinusitis was initially diagnosed due to thickened left frontal sinus mucosa on computed tomography (CT); however, there was no improvement after antibiotic intake. Repeat CT showed edematous inflammation of the nasal septum; biopsy of this site demonstrated erosion and infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils in the hyaline cartilage. Relapsing polychondritis was confirmed by the modified McAdam's criteria and can be diagnosed at an early stage by nasal septum biopsy; it should be considered as a differential diagnosis in patients presenting with nasal symptoms alone or persistent sinus symptoms. PMID:26843866

  9. Discovery of potent wall teichoic acid early stage inhibitors.

    PubMed

    Labroli, Marc A; Caldwell, John P; Yang, Christine; Lee, Sang Ho; Wang, Hao; Koseoglu, Sandra; Mann, Paul; Yang, Shu-Wei; Xiao, Jing; Garlisi, Charles G; Tan, Christopher; Roemer, Terry; Su, Jing

    2016-08-15

    The widespread emergence of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically eroded the efficacy of current β-lactam antibiotics and created an urgent need for novel treatment options. Using an S. aureus phenotypic screening strategy, we have identified small molecule early stage wall teichoic acid (WTA) pathway-specific inhibitors predicted to be chemically synergistic with β-lactams. These previously disclosed inhibitors, termed tarocins, demonstrate by genetic and biochemical means inhibition of TarO, the first step in WTA biosynthesis. Tarocins demonstrate potent bactericidal synergy in combination with broad spectrum β-lactam antibiotics across diverse clinical isolates of methicillin-resistant Staphylococci. The synthesis and structure-activity relationships (SAR) of a tarocin series will be detailed. Tarocins and other WTA inhibitors may provide a rational strategy to develop Gram-positive bactericidal β-lactam combination agents active against methicillin-resistant Staphylococci. PMID:27436582

  10. Frontiers in Radiotherapy for Early-Stage Invasive Breast Cancer

    PubMed Central

    Fisher, Christine M.; Rabinovitch, Rachel

    2014-01-01

    The development of breast-conserving treatment for early-stage breast cancer is one of the most important success stories in radiation oncology in the latter half of the twentieth century. Lumpectomy followed by radiotherapy provides an appealing alternative to mastectomy for many women. In recent years, there has been a shift in clinical investigational focus toward refinements in the methods of delivering adjuvant radiotherapy that provide shorter, more convenient schedules of external-beam radiotherapy and interstitial treatment. Expedited courses of whole-breast treatment have been demonstrated to be equivalent to traditional lengthier courses in terms of tumor control and cosmetic outcome and to provide an opportunity for cost efficiencies. PMID:25113764

  11. SBRT in operable early stage lung cancer patients

    PubMed Central

    Andratschke, Nicolaus; Guckenberger, Matthias

    2014-01-01

    Since decades the gold standard for treatment of early stage non-small cell lung cancer (NSCLC) is surgical lobectomy plus mediastinal lymph node dissection. Patients in worse health status are treated with sublobar resection or radiation treatment. With development of stereotactic-body-radiotherapy (SBRT), outcome of patients treated with radiation was substantially improved. Comparison of SBRT and surgical techniques is difficult due to the lack of randomized trials. However, all available evidence in form of case control studies of population based studies show equivalence between sublobar resection and SBRT indicating that SBRT—when performed by a trained and experienced team—should be offered to all high-risk surgical patients. For patients not willing to take the risk of lobectomy and therefore refusing surgery, SBRT is an excellent treatment option. PMID:25806303

  12. 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)

  13. 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.

  14. WHITE MATTER DEVELOPMENT IN THE EARLY STAGES OF PSYCHOSIS

    PubMed Central

    Peters, Bart D.; Karlsgodt, Katherine H.

    2014-01-01

    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. PMID:24893908

  15. Systematic characterization of small RNAome during zebrafish early developmental stages

    PubMed Central

    2014-01-01

    Background During early vertebrate development, various small non-coding RNAs (sRNAs) such as MicroRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) are dynamically expressed for orchestrating the maternal-to-zygotic transition (MZT). Systematic analysis of expression profiles of zebrafish small RNAome will be greatly helpful for understanding the sRNA regulation during embryonic development. Results We first determined the expression profiles of sRNAs during eight distinct stages of early zebrafish development by sRNA-seq technology. Integrative analyses with a new computational platform of CSZ (characterization of small RNAome for zebrafish) demonstrated an sRNA class transition from piRNAs to miRNAs as development proceeds. We observed that both the abundance and diversity of miRNAs are gradually increased, while the abundance is enhanced more dramatically than the diversity during development. However, although both the abundance and diversity of piRNAs are gradually decreased, the diversity was firstly increased then rapidly decreased. To evaluate the computational accuracy, the expression levels of four known miRNAs were experimentally validated. We also predicted 25 potentially novel miRNAs, whereas two candidates were verified by Northern blots. Conclusions Taken together, our analyses revealed the piRNA to miRNA transition as a conserved mechanism in zebrafish, although two different types of sRNAs exhibit distinct expression dynamics in abundance and diversity, respectively. Our study not only generated a better understanding for sRNA regulations in early zebrafish development, but also provided a useful platform for analyzing sRNA-seq data. The CSZ was implemented in Perl and freely downloadable at: http://csz.biocuckoo.org. PMID:24507755

  16. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    PubMed

    Kang, Guhyun; Hwang, Woo Cheol; Do, In-Gu; Wang, Kai; Kang, So Young; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Jang, Jiryeon; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Min Ji; Kim, Seonwoo; Park, Cheol Keun; Kim, Kyoung-Mee

    2013-01-01

    Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  17. 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.

  18. 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. PMID:26351964

  19. Clinical therapeutic strategies for early stage of diabetic kidney disease

    PubMed Central

    Kitada, Munehiro; Kanasaki, Keizo; Koya, Daisuke

    2014-01-01

    Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuous screening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression. PMID:24936255

  20. Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats.

    PubMed

    Jo, Woori; Yu, Eun-Sil; Chang, Minsun; Park, Hyun-Kyu; Choi, Hyun-Ji; Ryu, Jae-Eun; Jang, Sungwoong; Lee, Hyo-Ju; Jang, Ja-June; Son, Woo-Chan

    2016-01-01

    Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)‑induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma‑specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S‑transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK‑dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high‑risk patients, including chronic hepatitis and cirrhosis.

  1. Multiscale Investigations of the Early Stage Oxidation on Cu Surfaces

    NASA Astrophysics Data System (ADS)

    Zhu, Qing; Xiao, Penghao; Lian, Xin; Yang, Shen-Che; Henkelman, Grame; Saidi, Wissam; Yang, Judith; University of Pittsburgh Team; University of Texas at Austin Team

    Previous in situ TEM experiments have shown that the oxidation of the three low index Cu surfaces (100), (110) and (111) exhibit different oxide nucleation rates, and the resulting oxides have 3-dimensional (3D) island shapes or 2D rafts under different conditions. In order to better understand these results, we have investigated the early stages of Cu oxidation using a multiscale computational approach that employs density functional theory (DFT), reactive force field (ReaxFF), and kinetic Mote Carlo (KMC). With DFT calculation, we have compared O2 dissociation barriers on Cu (100), (110) and (111) surfaces at high oxygen coverage to evaluate the kinetic barrier of sublayer oxidization. We found that O2 dissociation barriers on Cu(111) surface are all lower than those on (110) and (100) surfaces. This trend agrees with experimental observations that (111) surface is easier to oxidize. These DFT calculated energy barriers are then incorporated into KMC simulations. The large scale ReaxFF molecular dynamics and KMC simulations detail the oxidation dynamics of the different Cu surfaces, and show the formation of various oxide morphologies that are consistent with experimental observations.

  2. 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

  3. Prevalence of psychiatric disorders in early stages of HIV infection.

    PubMed

    Brown, G R; Rundell, J R; McManis, S E; Kendall, S N; Zachary, R; Temoshok, L

    1992-01-01

    As part of a military universal HIV screening program, 442 men were assessed for the presence of DSM-III-R defined psychiatric disorders and symptoms of anxiety and depression after notification of HIV seroconversion. Of them, 84.4% were in the earliest, asymptomatic stages of disease at the time of interview (96% did not have AIDS). The Structured Clinical Interview for DSM-III-R and Structured Interview Guide for the Hamilton Anxiety and Depression Scales were used. Relevant comparisons were made to Epidemiologic Catchment Area prevalence data. HIV seropositive men were more likely than age-matched men in the community to have current diagnoses of major depression (ages 18-44) and anxiety disorders (ages 25-44). Higher lifetime rates of major depression and alcohol use disorder, and high current prevalence of sexual dysfunction (21.7%) were noted. We conclude that men who become HIV seropositive have high rates of mood and substance use disorders prior to knowledge of seroconversion, and that early in the course of HIV infection men are at risk for developing major depression, anxiety disorders, and disorders of sexual desire. PMID:1438661

  4. 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.

  5. Metformin inhibits early stage diethylnitrosamine-induced hepatocarcinogenesis in rats

    PubMed Central

    JO, WOORI; YU, EUN-SIL; CHANG, MINSUN; PARK, HYUN-KYU; CHOI, HYUN-JI; RYU, JAE-EUN; JANG, SUNGWOONG; LEE, HYO-JU; JANG, JA-JUNE; SON, WOO-CHAN

    2016-01-01

    Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)-induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma-specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S-transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK-dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high-risk patients, including chronic hepatitis and cirrhosis. PMID:26548419

  6. 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. PMID:26988891

  7. 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. PMID:20932909

  8. 77 FR 74908 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-18

    ... . Read only examples of these forms may be found at www.sba.gov/content/application-forms . III. Early... will allocate available leverage across all FY 2013 Early Stage SBICs on a pro rata basis. Early Stage....gov/content/earlystage-model-partnership-agreement . Applicants must use the Model LPA as a...

  9. 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.

  10. Manometric investigation of anorectal function in early and late stage Parkinson's disease

    PubMed Central

    Bassotti, G.; Maggio, D.; Battaglia, E.; Giulietti, O.; Spinozzi, F.; Reboldi, G.; Serra, A. M.; Emanuelli, G.; Chiarioni, G.

    2000-01-01

    Abnormal gastrointestinal function is relatively frequent in Parkinson's disease, and constipation is a disturbing symptom in many patients. However, it remains to be established whether anorectal abnormalities are characteristic of the late stages of the disease. Clinical and anorectal manometric function were investigated in groups of early and late stage parkinsonian patients. Thirty one patients (19 men, 12 women, age range 22 to 89 years) entered the study. The disease severity was assessed by Hoehn and Yahr staging: there were four (12.9%) stage I, seven (22.6%) stage II, 10 (32.2%) stage III, and 10 (32.2%) stage IV patients. Anorectal variables were measured by standard manometric equipment and techniques. Values obtained in early stage patients (Hoehn and Yahr stage I and II) were compared with those obtained in late stage patients (Hoehn and Yahr stage III and IV). Overall, more than 70% of patients complained of chronic constipation, with chronic laxative use reported in more than 30%. Late stage patients were slightly older than their early stage counterparts. Pelvic floor dyssynergia was documented in more than 60% of patients. Manometric variables were not different in the two groups. In conclusion, defecatory dysfunction is frequent in Parkinson's disease, it is not confined to late stage patients, and it is found early in the course of the disease. This has potential implications for a targeted therapeutic approach.

 PMID:10811703

  11. Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma.

    PubMed

    Li, Tao; Wang, Shu-Kang; Zhi, Xu-Ting; Zhou, Jian; Dong, Zhao-Ru; Zhang, Zong-Li; Sun, Hui-Chuan; Ye, Qing-Hai; Fan, Jia

    2016-01-01

    Although cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC), the association between cholecystectomy and prognosis of HCC patients underwent curative resection has never been examined. Through retrospective analysis of the data of 3933 patients underwent curative resection for HCC, we found that cholecystectomy was an independent prognostic factor for recurrence-free survival (RFS) of patients at early stage (BCLC stage 0/A) (p = 0.020, HR: 1.29, 95% CI: 1.04-1.59), and the 1-, 3-, 5-year RFS rates for patients at early stage were significantly worse in cholecystectomy group than in non-cholecystectomy group (80.5%, 61.8%, 52.0% vs 88.2%, 68.8%, 56.8%, p = 0.033). The early recurrence rate of cholecystectomy group was significantly higher than that of non-cholecystectomy group for patients at early stage (59/47 vs 236/333, p = 0.007), but not for patients at advanced stage (BCLC stage C) (p = 0.194). Multivariate analyses showed that cholecystectomy was an independent risk factor for early recurrence (p = 0.005, HR: 1.52, 95% CI: 1.13-2.03) of early stage HCC, but not for late recurrence (p = 0.959). In conclusion, cholecystectomy is an independent predictor for early recurrence and is associated with poorer RFS of early stage HCC. Removal of normal gallbladder during HCC resection may be avoided for early stage patients. PMID:27320390

  12. Active compressive intraoceanic deformation: early stages of ophiolites emplacement?

    NASA Astrophysics Data System (ADS)

    Chamot-Rooke, Nicolas; Delescluse, Matthias; Montési, Laurent

    2010-05-01

    investigate the very early stages of formation of faulted oceanic bodies that may further be incorporated into mountain belts as ophiolites. They allow to discuss rates and duration of deformation, diffuse vs localized deformation, re-activation vs neo-formed faults, serpentinization and thermal regime, spacing of minor and major thrust faults. Delescluse, M., L. G. J. Montesi, and N. Chamot-Rooke (2008) Fault reactivation and selective abandonment in the oceanic lithosphere. Geophys. Res. Lett., v. 35. Delescluse, M., and N. Chamot-Rooke (2008) Serpentinization pulse in the actively deforming Central Indian Basin. Earth Planet. Sci. Lett., v. 276, p. 140-151. Eittreim, S. L., and J. Ewing (1972), Mid-Plate Tectonics in the Indian Ocean, J. Geophys. Res., 77(32), 6413-6421.

  13. 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.

  14. Degradation phase of apoptosis during the early stages of human metanephros development.

    PubMed

    Wagner, Filip; Erdösová, Bela; Kylarová, Dana

    2004-12-01

    Apoptosis as a vital process is necessary for human intrauterine development. Not only the induction and course of apoptosis, but engulfment of the apoptotic cells (bodies) were the centre of our interest. Macrophages were detected in the early stages of human intrauterine development and the role of macrophages in the clearance of apoptotic cells in the early stages of human metanephros development was confirmed.

  15. Setting the Stage for Lifetime Physical Activity in Early Childhood

    ERIC Educational Resources Information Center

    Schneider, Holly; Lounsbery, Monica

    2008-01-01

    The purpose of this article is to provide a rationale and suggestions for emphasizing health-related physical education in preschool settings. In order to accomplish this, it will examine what is currently known about early childhood physical activity, as well as the existing professional preparation and accreditation standards for early childhood…

  16. A Four-Stage Method for Developing Early Interventions for Alcohol among Aboriginal Adolescents

    ERIC Educational Resources Information Center

    Mushquash, Christopher J.; Comeau, M. Nancy; McLeod, Brian D.; Stewart, Sherry H.

    2010-01-01

    This paper details a four-stage methodology for developing early alcohol interventions for at-risk Aboriginal youth. Stage 1 was an integrative approach to Aboriginal education that upholds Aboriginal traditional wisdom supporting respectful relationships to the Creator, to the land and to each other. Stage 2 used quantitative methods to…

  17. 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

  18. Early feeding: setting the stage for healthy eating habits.

    PubMed

    Mennella, Julie A; Ventura, Alison K

    2011-01-01

    Food habits, an integral part of all cultures, have their beginnings during early life. This chapter reviews the development of the senses of taste and smell, which provide information on the flavor of foods, and discusses how children's innate predispositions interact with early-life feeding experiences to form dietary preferences and habits. Young children show heightened preferences for foods that taste sweet and salty and rejection of that which tastes bitter. These innate responses are salient during development since they likely evolved to encourage children to ingest that which is beneficial, containing needed calories or minerals, and to reject that which is harmful. Early childhood is also characterized by plasticity, partially evidenced by a sensitive period during early life when infants exhibit heightened acceptance of the flavors experienced in amniotic fluid and breast milk. While learning also occurs with flavors found in formulae, it is likely that this sensitive period formed to facilitate acceptance of and attraction to the flavors of foods eaten by the mother. A basic understanding of the development and functioning of the chemical senses during early childhood may assist in forming evidence-based strategies to improve children's diets. PMID:22044898

  19. 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'…

  20. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    PubMed

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS.

  1. 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.

  2. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    PubMed

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS. PMID:23126275

  3. 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.

  4. 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…

  5. 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…

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

    SciTech Connect

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

    2006-12-15

    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 N{sub tot}{approx}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/l{sup 2}. The suppression is much smaller for N{sub tot}>59, therefore if the observable suppression originates in the fast roll stage, there is the upper bound N{sub tot}{approx}59.

  7. [Rehabilitation method for churg-strauss syndrome from early stage: considering functional prognosis of mononeuritis multiplex].

    PubMed

    Hashida, Goichi; Kan, Akiko; Inoue, Satoru; Abe, Kazuo

    2006-05-01

    We report our rehabilitation experience for two patients with Churg-Strauss syndrome (CSS). To improve their functional prognoses, we started rehabilitation program compensating for their activity of daily livings from their early stage. Also, we paid special attention to prescribed drug effect and adverse effect. Since patients with the mononeuritis multiplex have restricted weakness in the muscles ruled by a specific nerve, rehabilitation approaches including orthoses should start to improve the compensatory ability of normal adjacent muscles even in their early stages. In addition, since functional improvement may be gradual and take some years from onset, we should start rehabilitation in their early stage to improve their functional prognoses.

  8. 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.

  9. [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. PMID:22678672

  10. 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.

  11. Perennial atopic rhinitis as an early stage of bronchial asthma.

    PubMed

    Gniazdowski, R

    1979-01-01

    Etiologic factors and incidence of bronchial hyperreactivity as a 'stigma' of bronchial asthma were studied in 237 patients suffering from perennial atopic rhinitis. All pateints underwent detailed laryngologic and allergologic examiniation and pulmonary function tests at rest, after exercise, and after histamine inhalation. Most often the patients were sensitized tungal allergens. Bronchial hyperreactivity, typical of bronchial asthma, was observed in 48.52% of patients. Results were analysed statistically. It was concluded that early institution of causal therapy can cure the symptoms of rhinitis and prevent evolution of the disease into atopic bronchial asthma in patients already suffering from bronchial hyperreactivity. PMID:495074

  12. Early-stage relaxation of electrons by phonon emission.

    NASA Astrophysics Data System (ADS)

    Castella, Hervé; Kuznetsov, A. V.; Wilkins, J. W.

    1998-03-01

    Pump-probe experiments give insight into the relaxation of electrons during the first femtoseconds after the optical excitation. A theoretical description of this early-time regime requires a proper treatment of retardation effects for the different scattering processes. The scattering of electrons by optical phonons is investigated within the S-matrix formalism.(A. V. Kuznetsov, Ann. Phys. 258), 157 (1997) This perturbative scheme is directly compared to the non-equilibrium Green's function technique of Kadanoff and Baym. The scheme is used to numerically compute both the interband polarization and the momentum distribution function for a bulk semiconductor excited by a short laser pulse.

  13. 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.

  14. 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. |

  15. 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.

  16. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD).

    PubMed

    Baruth, Joshua M; Casanova, Manuel F; Sears, Lonnie; Sokhadze, Estate

    2010-06-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors.

  17. 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

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

    PubMed

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

    2016-04-01

    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

  19. 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.

  20. 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. PMID:27372072

  1. 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.

  2. Analyses of the early stages of star formation

    NASA Astrophysics Data System (ADS)

    Lintott, Christopher John

    This thesis presents a study of the physical and chemical properties of star forming regions, both in the Milky Way and in the distant Universe, building on the existing astrochem- ical models developed by the group at UCL. Observations of the nearby star-forming region, L134A, which were carried out with the James Clark Maxwell Telescope (JCMT) in Hawai'i are compared to the predictions of a model of star formation from gas rich in atomic (rather than molecular) hydrogen. A similar model is used to investigate the effect of non-equilibrium chemistry on the derivation of the cosmic-ray ionization rate, an important parameter in controlling both the chemistry and the physics of star forming clumps. A collapse faster than free-fall is proposed as an explanation for differences be tween the distribution of CS and N2H+ in such regions. Moving beyond the Milky Way, JCMT observations of sulphur-bearing species in the nearby starburst galaxy, M82, are presented and compared with existing molecular observations of similar systems. M82 is a local anlogue for star forming systems in the early Universe, many of which have star formation rates several thousand times that of the Milky Way. A model which treats the molecular gas in such systems as an assembly of 'hot cores' (protostellar cores which have a distinctive chemical signature) has been developed, and is used to predict the abundance of many species. An application of this model is used to explain the observed deviation in the early Universe from the otherwise tight relation between infrared and HCN luminosity via relatively recent star formation from near-primordial gas. Many of the stars formed in the early Universe must now be in massive elliptical systems, and work on the structure of these systems is presented. Data from the Sloan Digital Sky Survey is analysed to show that such galaxies have cores dominated by baryons rather than dark matter, and the dark matter profile is constrained by adiabatic contraction.

  3. Differentially expressed protein-coding genes and long noncoding RNA in early-stage lung cancer.

    PubMed

    Li, Ming; Qiu, Mantang; Xu, Youtao; Mao, Qixing; Wang, Jie; Dong, Gaochao; Xia, Wenjia; Yin, Rong; Xu, Lin

    2015-12-01

    Due to the application of low-dose computed tomography screening, more and more early-stage lung cancers have been diagnosed. Thus, it is essential to characterize the gene expression profile of early-stage lung cancer to develop potential biomarkers for early diagnosis and therapeutic targets. Here, we analyzed microarray data of 181 early-stage lung cancer patients. By comparing gene expression between different tumor and lymph node metastasis stages, we identified various differentially expressed protein-coding genes and long noncoding RNA (lncRNA) in the comparisons of T2 vs. T2 and N1- vs. N0-stage lung cancer. Functional analyses revealed that these differentially expressed genes were enriched in various tumorigenesis or metastasis-related pathways. Survival analysis indicated that two protein-coding genes, C7 and SCN7A, were significantly associated survival of lung cancer. Notably, a novel lncRNA, LINC00313, was highly expressed in both T2- and N1-stage lung cancers. On the other hand, LINC00313 was also upregulated in lung cancer and metastasized lung cancer tissues, compared with adjacent lung tissues and primary lung cancer tissues. Additionally, higher expression level of LINC00313 indicated poor prognosis of lung cancer (hazard ratio = 0.658). Overall, we characterized the expression profiles of protein-coding genes and lncRNA in early-stage lung cancer and found that LINC00313 could be a biomarker for lung cancer.

  4. Modelling early stages of relativistic heavy-ion collisions

    NASA Astrophysics Data System (ADS)

    Ruggieri, M.; Puglisi, A.; Oliva, L.; Plumari, S.; Scardina, F.; Greco, V.

    2016-05-01

    In this study we model early time dynamics of relativistic heavy ion collisions by an initial color-electric field which then decays to a plasma by the Schwinger mechanism. The dynamics of the many particles system produced by the decay is described by relativistic kinetic theory, taking into account the backreaction on the color field by solving self-consistently the kinetic and the field equations. Our main results concern isotropization and thermalization for a 1+1D expanding geometry. In case of small η/s (η/s ≲ 0.3) we find τisotropization ≈ 0.8 fm/c and τthermalization ≈ 1 fm/c in agreement with the common lore of hydrodynamics.

  5. 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

  6. A profile of identity in early-stage dementia and a comparison with healthy older people.

    PubMed

    Caddell, Lisa S; Clare, Linda

    2013-01-01

    The aim of the study was to determine whether people in the early stages of dementia experience their sense of identity differently to healthy older people and to examine whether different aspects of identity are related to each other in each group. This was a cross-sectional questionnaire-based study; 50 people with early-stage dementia and 50 age-matched people without dementia completed measures pertaining to different aspects of identity. Measures of mood and self-esteem were also included so that any differences could be taken into account in the analysis. There were very few differences in identity between the groups. After differences in levels of anxiety were accounted for, there were no differences in scores on most measures of identity. However, people in the early stages of dementia scored significantly lower on one subtotal for one measure of identity, whereas healthy older adults reported significantly more identity-related distress than people in the early stages of dementia. For both groups, there were no associations between different aspects of identity. People in the early stages of dementia do not differ much from healthy older adults in terms of their identity. Since healthy older people experience more distress relating to identity, they may be more likely to benefit from some sort of intervention than people in the early stages of dementia. It might be useful to consider identity as consisting of multiple components in future studies, rather than assuming that one aspect of identity represents the overall experience of identity.

  7. 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.

  8. Preoperative staging and early postoperative complications in radical prostatectomy. Experiences in 35 cases.

    PubMed

    Romics, I; Bach, D; Widmann, T

    1994-01-01

    It is already a textbook item that in patients with prostatic cancer stage T1-T2 N0M0 radical prostatectomy is the only curative treatment. Radical prostatectomy is indicated also for patients in stage T3 N0M0 who underwent antiandrogenic (Fugerel) treatment for 3 months with the aim of reducing tumour volume. In the following 35 cases will be scrutinized, with special regard to preoperative staging and early postoperative complications.

  9. Prediction of invasion from the early stage of an epidemic.

    PubMed

    Pérez-Reche, Francisco J; Neri, Franco M; Taraskin, Sergei N; Gilligan, Christopher A

    2012-09-01

    Predictability of undesired events is a question of great interest in many scientific disciplines including seismology, economy and epidemiology. Here, we focus on the predictability of invasion of a broad class of epidemics caused by diseases that lead to permanent immunity of infected hosts after recovery or death. We approach the problem from the perspective of the science of complexity by proposing and testing several strategies for the estimation of important characteristics of epidemics, such as the probability of invasion. Our results suggest that parsimonious approximate methodologies may lead to the most reliable and robust predictions. The proposed methodologies are first applied to analysis of experimentally observed epidemics: invasion of the fungal plant pathogen Rhizoctonia solani in replicated host microcosms. We then consider numerical experiments of the susceptible-infected-removed model to investigate the performance of the proposed methods in further detail. The suggested framework can be used as a valuable tool for quick assessment of epidemic threat at the stage when epidemics only start developing. Moreover, our work amplifies the significance of the small-scale and finite-time microcosm realizations of epidemics revealing their predictive power. PMID:22513723

  10. 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…

  11. Thyroid gland development in Rachycentron canadum during early life stages.

    PubMed

    Otero, Adriana P S; Rodrigues, Ricardo V; Sampaio, Luís A; Romano, Luis A; Tesser, Marcelo B

    2014-09-01

    The aim of this study was to describe the ontogeny of thyroid follicles in cobia Rachycentron canadum. Larvae were sampled daily (n=15 - 20) from hatching until 15 dah (days after hatching). Following, larvae were sampled every two days by 28 dah; a new sample was taken at 53 dah. The samples were dehydrated, embedded in Paraplast, and sections of 3 µm were dewaxed, rehydrated and stained with HE and PAS. A single follicle was already present 1 dah and three follicles were found 8 dah. The number of follicles increased up to 19 on 53 dah. The diameter of follicles and follicular cell height were lower 1 dah (6.83 ± 1.00 and 4.6 ± 0.01 µm), but increased from 8 dah (24.03 ± 0.46 µm e 6.43 ± 0.46 µm). From 8 dah, the presence of reabsorption vesicles was observed in the colloid and from the 19 dah some follicles did not present colloid. The early thyroid follicle appearance in cobia larvae as well as the high quantity of follicles without colloid and/or with vesicles even after the metamorphosis, might be the explanation of the fast growth of the cobia.

  12. [Urinalysis in patients at the early stage of acute pancreatitis].

    PubMed

    Rybak, Katarzyna; Sporek, Mateusz; Gala-Błądzińska, Agnieszka; Mazur-Laskowska, Małgorzata; Dumnicka, Paulina; Walocha, Jerzy; Drożdż, Ryszard; Kuźniewski, Marek; Ceranowicz, Piotr; Kuśnierz-Cabala, Beata

    2016-01-01

    Urinalysis is a routine and cheap laboratory test that provides clinically useful information in patients with acute abdominal conditions, including acute pancreatitis. The aim of the study was to assess the relationships between the results of urinalysis and the course of the disease among 65 patients with acute pancreatitis (34 men and 31 women, mean age 61 ± 19 years) at the early phase of the disease, i.e. during the first 72 hours from the onset of symptoms. Mild acute pancreatitis was diagnosed in 47 patients, moderately severe in 13 and severe in 5. The most prevalent abnormalities were proteinuria (43% of patients), high urinary bilirubin (20%), erythrocytes (18%), glucose (18%) and leukocytes (17%). High urinary protein and low specific gravity were associated with more severe acute disease and with acute kidney injury. The severity of bilirubinuria and proteinuria were positively correlated with urine concentrations of neutrophil gelatinase associated lipocalin (NGAL). Urinalysis should be routinely performed in patients with acute pancreatitis. PMID:27197429

  13. A Computational Cognitive Biomarker for Early-Stage Huntington's Disease.

    PubMed

    Wiecki, Thomas V; Antoniades, Chrystalina A; Stevenson, Alexander; Kennard, Christopher; Borowsky, Beth; Owen, Gail; Leavitt, Blair; Roos, Raymund; Durr, Alexandra; Tabrizi, Sarah J; Frank, Michael J

    2016-01-01

    Huntington's disease (HD) is genetically determined but with variability in symptom onset, leading to uncertainty as to when pharmacological intervention should be initiated. Here we take a computational approach based on neurocognitive phenotyping, computational modeling, and classification, in an effort to provide quantitative predictors of HD before symptom onset. A large sample of subjects-consisting of both pre-manifest individuals carrying the HD mutation (pre-HD), and early symptomatic-as well as healthy controls performed the antisaccade conflict task, which requires executive control and response inhibition. While symptomatic HD subjects differed substantially from controls in behavioral measures [reaction time (RT) and error rates], there was no such clear behavioral differences in pre-HD. RT distributions and error rates were fit with an accumulator-based model which summarizes the computational processes involved and which are related to identified mechanisms in more detailed neural models of prefrontal cortex and basal ganglia. Classification based on fitted model parameters revealed a key parameter related to executive control differentiated pre-HD from controls, whereas the response inhibition parameter declined only after symptom onset. These findings demonstrate the utility of computational approaches for classification and prediction of brain disorders, and provide clues as to the underlying neural mechanisms. PMID:26872129

  14. Biology of early life stages in cephalopod molluscs.

    PubMed

    von Boletzky, S

    2003-01-01

    Recent literature on embryonic and post-embryonic development, biology and behavioural ecology of juvenile cephalopods is reviewed. Emphasis is placed on biological processes. Life-history patterns and phylogenetic systematics, which are important for a proper understanding of the evolutionary history of the cephalopods, are only briefly touched upon. Egg sizes in cephalopods range from less than 1 mm to about 30 mm in diameter, so the hatchlings emerging from the largest eggs are bigger than the adults of pygmy squid, the smallest known cephalopods. Developmental durations from spawning to hatching range from a few days (for very small eggs developing at high temperatures) to one or possibly several years (for very large eggs developing at low temperatures). Such important differences notwithstanding, the morphogenetic processes are very similar in all cephalopod embryos, the major variant being the size of the so-called outer yolk sac, which may be rudimentary in extremely small embryos. Several questions concerning the timing of hatching in relation to the developmental stage attained, especially in terms of yok absorption, need clarification. These questions concern the elimination of the transient closure of the mouth, the final differentiation of digestive gland cells, and the removal of the tranquilliser effect of the perivitelline fluid necessary for the onset of the hatching behaviour. Cephalopod hatchlings are active predators. They refine their behavioural repertoires by learning from individual experience in dealing with prey and would-be predators. There is no truly larval phase, and the ecologically defined term paralarva should be used with caution. Given the considerable resource potential of cephalopods, investigations into dispersal and recruitment are of particular interest to fishery biology, but they are also important for ecological biogeography. The related studies of feeding and growth involve field sampling and tentative age determination

  15. Early stage cervical cancer: psychosocial and sexual outcomes of treatment.

    PubMed

    Cull, A; Cowie, V J; Farquharson, D I; Livingstone, J R; Smart, G E; Elton, R A

    1993-12-01

    Eighty-three women, mean age 45 years, successfully treated by surgery (S) or radiotherapy (RT) for stage 1b cervical cancer were assessed a mean of 97 weeks post treatment. Forty to 50% reported persistent tiredness, lack of energy and weight gain. Sixty per cent had not resumed their full premorbid functional status. Mean scores for anxiety and depression were higher than general population means and this sample scored higher for psychological distress than published data quoted for disease free cancer patients. These women reported many concerns about cervical cancer, most commonly fear of recurrent disease (91%). More than one-third blamed themselves for the disease. There were no significant differences in functional outcome or psychological status between treatment groups or by age or time since treatment. Psychological distress scores were significantly correlated with physical complaints (P < 0.001) and functional outcomes (P < 0.02). For the 61 women who were sexually active, sexual function post-treatment was rated as significantly poorer than subjectively recalled premorbid sexual function (P < 0.005). RT treated patients were more likely to report pain on intercourse and loss of enjoyment. Psychological as well as physical problems were highly correlated with sexual outcome (P < 0.01) 44% were unable to talk adequately with their partners about their experience. The majority felt they needed more information about cervical cancer, its treatment and how to help themselves rehabilitate. Forty-nine per cent would have liked to have had counselling. Even with the same physical morbidity the functional, emotional and sexual status of these women could be improved by giving more attention to their psychological and sexual concerns. PMID:8260376

  16. 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

  17. Seismic anisotropy and texture development during early stages of subduction

    NASA Astrophysics Data System (ADS)

    Di Leo, Jeanette; Walker, Andrew; Li, Zhong-Hai; Wookey, James; Ribe, Neil; Kendall, J.-Michael; Tommasi, Andréa

    2014-05-01

    Shear wave splitting measurements are frequently used to infer upper mantle flow trajectory, based on the fact that, under strain, olivine develops lattice-preferred orientation (LPO) textures in the convecting mantle. However, such inferences ought to be made carefully, since the relationship between splitting fast polarisation and olivine LPO depends on several factors, one of them being the deformation history of the volume of mantle in question. This is especially the case in regions such as subduction zones, where complex and time-dependent mantle flow occurs. Here, we present an integrated model to simulate strain-history-dependent LPO development and measure the resulting shear wave splitting in a subduction setting. We do this for a subduction model that approximates the geometry of the double-sided Molucca Sea subduction system in eastern Indonesia. We test a single-sided and a double-sided subduction case, and compare the results to shear wave splitting observations of this region. Since the subduction zone is fairly young, early textures from the slab's descent from the near-surface to the bottom of the mantle transition zone - which we simulate in our models - have not yet been overprinted by subsequent continuous flow. It further allows us to test the significance of the double-sided geometry, i.e., the need for a rear barrier to achieve trench-parallel sub-slab mantle flow. We simulate olivine LPO evolution in polycrystalline aggregates as they move and deform along pathlines extracted from a 3-D mantle flow model. Interactions between crystals are described using the visco-plastic self-consistent (VPSC) approach. Unlike previous studies, we consider the entire subduction history from subduction initiation onwards. After calculating elastic properties associated with LPO textures, we estimate the resulting splitting parameters (fast direction φ, delay time δt) for synthetic SKS phases. Our models demonstrate that complex, backazimuth

  18. Cognitive and behavioral assessment in the early stages of neurodegenerative extrapyramidal syndromes.

    PubMed

    Borroni, B; Turla, M; Bertasi, V; Agosti, C; Gilberti, N; Padovani, A

    2008-01-01

    Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration Syndrome (CBDS) are the most common neurodegenerative extrapyramidal syndromes. Beyond motor symptoms, cognitive dysfunctions and behavioral disturbances are reported. Neuropsychological and neuropsychiatry features in the early stages, however, are under-investigated, and few comparison studies are available yet. The aim of the present study was to evaluate the cognitive and behavioral profile in the early stages of neurodegenerative extrapyramidal syndromes. Thirty-nine PD, 27 DLB, 16 CBDS, and 24 PSP were recruited. Groups were matched for global cognitive and motor impairment. The overall sample showed a common neuropsychological core characterized by visuospatial deficits. Although in the early stage of the disease, a high presence of behavioral disturbances was detected, depression and anxiety were the most common disorders, followed by apathy and sleep disturbances. The observation of overlapping clinical entities points the attention on the need of adjunctive diagnostic markers for early differential diagnosis.

  19. [Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

    PubMed

    Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

    2013-01-01

    A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

  20. 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

  1. The relationship between local recurrence and death in early-stage breast cancer.

    PubMed

    Sopik, Victoria; Nofech-Mozes, Sharon; Sun, Ping; Narod, Steven A

    2016-01-01

    To examine the relationship between local recurrence and breast cancer mortality in women with early-stage breast cancer. We studied 1675 women with stage 0 (DCIS), stage I or stage II breast cancer who were treated with breast-conserving surgery at Women's College Hospital between 1987 and 2009. For each patient, we obtained information on age at diagnosis, tumour size, lymph node status, tumour grade, lymphovascular invasion, oestrogen receptor status, progesterone receptor status, HER2 status and treatments received (radiotherapy, chemotherapy and tamoxifen). Patients were followed from the date of diagnosis until local recurrence, death from breast cancer or the date of last follow-up. We used the Kaplan-Meier method to estimate 15-year local recurrence-free and breast cancer-specific survival rates for each stage at diagnosis. For each stage, the two rates were compared. After a mean follow-up of 13.1 years, 243 women (14.5 %) experienced a local recurrence and 281 women (16.8 %) died of breast cancer. The 15-year actuarial rate of local recurrence was 16 % for women with DCIS, 15 % for women with stage I cancer and 16 % for women with stage II cancer. The 15-year breast cancer-specific mortality rate was 3 % for women with DCIS, 10 % for women with stage I breast cancer and 30 % for women with stage II breast cancer. After experiencing a local recurrence, the 15-year breast cancer mortality rate was 16 % for women with DCIS, 32 % for women with stage I breast cancer and 59 % for women with stage II breast cancer. Across the spectrum of the early stages of breast cancer, the risk of local recurrence does not correlate with the risk of death from breast cancer. After local recurrence, the risk of death from breast cancer depends on the initial stage at diagnosis.

  2. 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 ...

  3. Effects of nicotine on a rat model of early stage osteoarthritis

    PubMed Central

    Gu, Qiangrong; Li, Dong; Wei, Bo; Guo, Yang; Yan, Junwei; Mao, Fengyong; Zhang, Xiang; Wang, Liming

    2015-01-01

    The objective of the study was to investigate the effects of nicotine on articular cartilage degeneration and inflammation in a rat model of early stage osteoarthritis (OA), using T2 mapping. In this study, a rat model of early stage OA was established by immobilizing the left knee joints of adult male rats for two weeks. Subsequently, rats were fed with nicotine for two and four weeks. Changes in the articular cartilage from the medial femoral condylar region of the knee were evaluated by gross observation and histological grading with the contents of cartilage matrix detected. T2 values of the articular cartilage were estimated through high-field magnetic resonance imaging (MRI) (7.0T). Levels of serum tumor necrosis factor-α (TNF-α) were assessed by ELISA. The expression of TNF-α and the cholinergic receptor, α7nAChR, in the synovial tissue was measured by RT-PCR. Nicotine treatment ameliorated cartilage destruction, promoted matrix production, reduced the serum level of TNF-α and the expression of TNF-α in the synovial tissue, and increased the expression of α7nAChR in the synovial tissue in the rat model of early stage OA. In conclusion, nicotine prevented cartilage damage and had an anti-inflammatory effect in a rat model of early stage OA. Thus nicotine may have potential as a therapeutic strategy for early stage OA. PMID:26097542

  4. 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.

  5. Using physiology and behaviour to understand the responses of fish early life stages to toxicants.

    PubMed

    Sloman, K A; McNeil, P L

    2012-12-01

    The use of early life stages of fishes (embryos and larvae) in toxicity testing has been in existence for a long time, generally utilizing endpoints such as morphological defects and mortality. Behavioural endpoints, however, may represent a more insightful evaluation of the ecological effects of toxicants. Indeed, recent years have seen a considerable increase in the use of behavioural measurements in early life stages reflecting a substantial rise in zebrafish Danio rerio early life-stage toxicity testing and the development of automated behavioural monitoring systems. Current behavioural endpoints identified for early life stages in response to toxicant exposure include spontaneous activity, predator avoidance, capture of live food, shoaling ability and interaction with other individuals. Less frequently used endpoints include measurement of anxiogenic behaviours and cognitive ability, both of which are suggested here as future indicators of toxicant disruption. For many simple behavioural endpoints, there is still a need to link behavioural effects with ecological relevance; currently, only a limited number of studies have addressed this issue. Understanding the physiological mechanisms that underlie toxicant effects on behaviour so early in life has received far less attention, perhaps because physiological measurements can be difficult to carry out on individuals of this size. The most commonly established physiological links with behavioural disruption in early life stages are similar to those seen in juveniles and adults including sensory deprivation (olfaction, lateral line and vision), altered neurogenesis and neurotransmitter concentrations. This review highlights the importance of understanding the integrated behavioural and physiological response of early life stages to toxicants and identifies knowledge gaps which present exciting areas for future research.

  6. Estimates of the duration of the early and late stage of gambiense sleeping sickness

    PubMed Central

    Checchi, Francesco; Filipe, João AN; Haydon, Daniel T; Chandramohan, Daniel; Chappuis, François

    2008-01-01

    Background The durations of untreated stage 1 (early stage, haemo-lymphatic) and stage 2 (late stage, meningo-encephalitic) human African trypanosomiasis (sleeping sickness) due to Trypanosoma brucei gambiense are poorly quantified, but key to predicting the impact of screening on transmission. Here, we outline a method to estimate these parameters. Methods We first model the duration of stage 1 through survival analysis of untreated serological suspects detected during Médecins Sans Frontières interventions in Uganda and Sudan. We then deduce the duration of stage 2 based on the stage 1 to stage 2 ratio observed during active case detection in villages within the same sites. Results Survival in stage 1 appears to decay exponentially (daily rate = 0.0019; mean stage 1 duration = 526 days [95%CI 357 to 833]), possibly explaining past reports of abnormally long duration. Assuming epidemiological equilibrium, we estimate a similar duration of stage 2 (500 days [95%CI 345 to 769]), for a total of nearly three years in the absence of treatment. Conclusion Robust estimates of these basic epidemiological parameters are essential to formulating a quantitative understanding of sleeping sickness dynamics, and will facilitate the evaluation of different possible control strategies. PMID:18261232

  7. Laparoscopic surgery on broken points for uterine sarcoma in the early stage decrease prognosis.

    PubMed

    Liu, Hong; Zhu, Yi; Zhang, Guo-Nan; Wang, Chang; Li, Chao; Shi, Yu

    2016-01-01

    Uterine sarcoma, a rare solid tumor in uterus, is difficult to identify in the early stage from some benign uterine tumors, such as uterine fibroids. Hence, uterine sarcoma may be treated in the same way as uterine fibroids; and this may not be found until pathological diagnosis. Consequently, this can lead to tumor's abdominal spread, planting and local invasive growth, resulting in an early uterine sarcoma, an increased relapse rate after surgery and a decreased survival. Therefore, it's important to avoid these unintended and iatrogenic complications through an accurate diagnosis and an appropriate surgical approach. The surgical staging and a complete resection of the tumor are both important for patients' prognosis. In this review, we will discuss the laparoscopic surgery for uterine sarcoma in the early stage and patients' prognosis. PMID:27503773

  8. Laparoscopic surgery on broken points for uterine sarcoma in the early stage decrease prognosis

    PubMed Central

    Liu, Hong; Zhu, Yi; Zhang, Guo-Nan; Wang, Chang; Li, Chao; Shi, Yu

    2016-01-01

    Uterine sarcoma, a rare solid tumor in uterus, is difficult to identify in the early stage from some benign uterine tumors, such as uterine fibroids. Hence, uterine sarcoma may be treated in the same way as uterine fibroids; and this may not be found until pathological diagnosis. Consequently, this can lead to tumor’s abdominal spread, planting and local invasive growth, resulting in an early uterine sarcoma, an increased relapse rate after surgery and a decreased survival. Therefore, it’s important to avoid these unintended and iatrogenic complications through an accurate diagnosis and an appropriate surgical approach. The surgical staging and a complete resection of the tumor are both important for patients’ prognosis. In this review, we will discuss the laparoscopic surgery for uterine sarcoma in the early stage and patients’ prognosis. PMID:27503773

  9. 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. PMID:26526165

  10. Validity of linear analysis in early-stage spinodal decomposition of a polymer mixture

    NASA Astrophysics Data System (ADS)

    Hayashi, Masaki; Jinnai, Hiroshi; Hashimoto, Takeji

    2000-08-01

    A two-step phase separation was imposed to a binary mixture of deuterated polybutadiene and protonated polyisoprene with nearly critical composition in the following way: the system was first subjected to phase separation via spinodal decomposition (SD) so that the system developed coexisting two phases characteristics of the late stage of SD (the first-step phase separation). It was then brought into a deeper quench so that both two phases again fell into spinodal region and hence further SD took place within each phase (the second-step phase separation at T2). In the very early stage after this second-step phase separation, the two-phase structure developed in the first-step phase separation was almost unchanged with time, but the composition fluctuation was newly developed within each phase, giving rise to an excess light scattering (LS) at large scattering vectors. The very early stage in this second-step phase separation process was studied by time-resolved LS. We found that the early-stage SD after the second-step phase separation at T2 can be well described by the linearized theory of SD. However the characteristic parameters, especially the collective diffusivity, obtained from the linear analysis, were different from those obtained by the single-step SD at T2 for the corresponding single-phase mixtures. The results unveil an intriguing effect of initial structure or space confinement on early stage SD, reflecting an intrinsically nonlinear phenomenon.

  11. Upregulation of α3β1-Integrin in Podocytes in Early-Stage Diabetic Nephropathy

    PubMed Central

    Sawada, Kaichiro; Kaneyama, Noriko; Shiraiwa, Sawako; Moriya, Hitomi; Miyatake, Han; Tanaka, Eitaro; Yamamoto, Naoyuki; Miyauchi, Masaaki; Kimura, Moritsugu; Wada, Takehiko; Fukagawa, Masafumi

    2016-01-01

    Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation of α3β1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels of α3β1-integrin in podocytes in early and advanced stages of DN. Methods. Surgical specimens from DN patients were examined by in situ hybridization, and the expression levels of α3- and β1-integrin subunits in glomeruli of early (n = 6) and advanced (n = 8) stages were compared with those of normal glomeruli (n = 5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-β1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined. Results. Podocytes of early-stage DN showed upregulation of α3- and β1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation of α3- and β1-integrin in HSMP cultured with TGF-β1. TGF-β1-stimulated HSMP also showed enhanced in vitro migration and attachment on collagen substrate. Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation of α3β1-integrin. PMID:27340677

  12. 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.

  13. Triaging early-stage lung cancer patients into non-surgical pathways: who, when, and what?

    PubMed Central

    Kong, Feng-Ming (Spring)

    2015-01-01

    More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternative treatments now available. These alternative treatments include radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous cryoablation therapy (PCT), photodynamic therapy (PDT) and external beam radiation therapy (EBRT), including stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy. We describe the established alternatives to surgical resection, their advantages and disadvantages, potential complications and efficacy. We then describe the optimal treatment approach for patients with early-stage NSCLC based on tumor operability, size and location. Finally, we discuss future directions and whether any alternative therapies will challenge surgical resection as the treatment of choice for patients with operable early-stage lung cancer. PMID:26380185

  14. 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.

  15. 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

  16. Robotic surgery for early stage cervical cancer: Evolution and current trends.

    PubMed

    Medlin, Erin E; Kushner, David M; Barroilhet, Lisa

    2015-12-01

    The management of early stage cervical cancer often includes surgery in the form of radical hysterectomy, radical trachelectomy, or radical parametrectomy. Surgical techniques have evolved to include minimal invasive approaches, and more recently, to include robotic assisted techniques. This review highlights the evolution of surgical management of early cervical cancer and specifically explores robotic assisted radical hysterectomy, radical trachelectomy, radical parametrectomy, and the role of neoadjuvant chemotherapy.

  17. Robotic surgery for early stage cervical cancer: Evolution and current trends.

    PubMed

    Medlin, Erin E; Kushner, David M; Barroilhet, Lisa

    2015-12-01

    The management of early stage cervical cancer often includes surgery in the form of radical hysterectomy, radical trachelectomy, or radical parametrectomy. Surgical techniques have evolved to include minimal invasive approaches, and more recently, to include robotic assisted techniques. This review highlights the evolution of surgical management of early cervical cancer and specifically explores robotic assisted radical hysterectomy, radical trachelectomy, radical parametrectomy, and the role of neoadjuvant chemotherapy. PMID:26768315

  18. Funding opportunities for clinical investigators in the early stages of career development in cardiovascular research.

    PubMed

    Mentz, Robert J; Becker, Richard C

    2013-11-01

    Contemporary cardiovascular research offers junior investigators the opportunity to explore the gamut of biomedical questions. Despite the recent reduction in the availability of funding mechanisms that have historically served as the primary pathways for investigators in the early stages of career development, there remain numerous traditional and non-traditional funding opportunities. This article highlights these opportunities in order to assist early career investigators in the development of a personalized research trajectory, which optimizes the potential for career success.

  19. [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.

  20. [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. PMID:23829961

  1. 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.

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

    PubMed

    Duffy, T A; Iwanowicz, L R; McCormick, S D

    2014-07-01

    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 (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 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 embryos. 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 plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages 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. PMID:24713117

  3. 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.

  4. Molecular responses to 17β-estradiol in early life stage salmonids.

    PubMed

    Marlatt, Vicki L; Sun, Jinying; Curran, Cat A; Bailey, Howard C; Kennedy, Chris K; Elphick, James R; Martyniuk, Christopher J

    2014-07-01

    Environmental estrogens (EE) are ubiquitous in many aquatic environments and biological responses to EEs in early developmental stages of salmonids are poorly understood compared to juvenile and adult stages. Using 17β-estradiol (E2) as a model estrogen, waterborne exposures were conducted on early life stage rainbow trout (Oncorhynchus mykiss; egg, alevin, swim-up fry) and both molecular and physiological endpoints were measured to quantify the effects of E2. To investigate developmental stage-specific effects, laboratory exposures of 1 μg/L E2 were initiated pre-hatching as eyed embryos or post-hatching upon entering the alevin stage. High mortality (∼90%) was observed when E2 exposures were initiated at the eyed embryo stage compared to the alevin stage (∼35% mortality), demonstrating stage-specific sensitivity. Gene expression analyses revealed that vitellogenin was detectable in the liver of swim-up fry, and was highly inducible by 1 μg/L E2 (>200-fold higher levels compared to control animals). Experiments also confirmed the induction of vitellogenin protein levels in protein extracts isolated from head and tail regions of swim-up fry after E2 exposure. These findings suggest that induction of vitellogenin, a well-characterized biomarker for estrogenic exposure, can be informative measured at this early life stage. Several other genes of the reproductive endocrine axis (e.g. estrogen receptors and androgen receptors) exhibited decreased expression levels compared to control animals. In addition, chronic exposure to E2 during the eyed embryo and alevin stages resulted in suppressive effects on growth related genes (growth hormone receptors, insulin-like growth factor 1) as well as premature hatching, suggesting that the somatotropic axis is a key target for E2-mediated developmental and growth disruptions. Combining molecular biomarkers with morphological and physiological changes in early life stage salmonids holds considerable promise for further

  5. 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…

  6. 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…

  7. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD)

    PubMed Central

    Baruth, Joshua M.; Casanova, Manuel F.; Sears, Lonnie; Sokhadze, Estate

    2012-01-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors. PMID:22563527

  8. 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...

  9. 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…

  10. 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)…

  11. Couple-Focused Group Intervention for Women With Early Stage Breast Cancer

    ERIC Educational Resources Information Center

    Manne, Sharon L.; Ostroff, Jamie S.; Winkel, Gary; Fox, Kevin; Grana, Generosa; Miller, Eric; Ross, Stephanie; Frazier, Thomas

    2005-01-01

    This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions…

  12. 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,…

  13. 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…

  14. A Comparison of Item Selection Rules at the Early Stages of Computerized Adaptive Testing.

    ERIC Educational Resources Information Center

    Chen, Shu-Ying; Ankenmann, Robert D.; Chang, Hua-Hua

    2000-01-01

    Compared five item selection rules with respect to the efficiency and precision of trait (theta) estimation at the early stages of computerized adaptive testing (CAT). The Fisher interval information, Fisher information with a posterior distribution, Kullback-Leibler information, and Kullback-Leibler information with a posterior distribution…

  15. 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…

  16. The Night before the LHC -thoughts about expectations in the early stage and beyond-

    SciTech Connect

    Nojiri, Mihoko M.

    2008-11-23

    I review recent developments on the use of m{sub T2} variables for SUSY parameter study, which might be useful for analyses of the data in the early stage of the LHC experiments. I will also mention some of recent interesting studies relevant to the SUSY analysis.

  17. 77 FR 25775 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-01

    ... also review the information at www.sba.gov/inv/earlystage which includes a list of frequently asked... Regulatory Capital, up to a maximum of $50 million. Early Stage SBICs must invest at least 50% of their... governing these SBICs may be found at www.sba.gov/inv/earlystage . DATES: In order to expedite licensing...

  18. "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…

  19. 76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... provide early stage venture capital financing to small businesses. The standard debenture is generally... operating history may qualify under this definition. The venture capital industry employs various... investment fund draws its initial capital from investors). Because of the cyclical nature of venture...

  20. 77 FR 25042 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... assets or cash flow for traditional bank funding. Although the venture capital industry provided over $22... form of SBA- guaranteed debentures to SBICs that plan to provide early stage venture capital financing... such as the Institutional Limited Partners Association, the National Venture Capital Association,...

  1. 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...

  2. 76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ...- creating startups and small firms, accelerate research, and address barriers to success for entrepreneurs... From the Federal Register Online via the Government Publishing Office ] SMALL BUSINESS ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage SBICs; Public Webinars AGENCY:...

  3. Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma

    PubMed Central

    Jang, Ye-Rang; Kim, Hyeyoung; Lee, Jeong-Moo; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    Backgrounds/Aims In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2). PMID:26693236

  4. Cationic gradient reversal and cytoskeleton-independent volume regulatory pathways define an early stage of apoptosis.

    PubMed

    Bortner, Carl D; Sifre, Maria I; Cidlowski, John A

    2008-03-14

    Cell shrinkage, or apoptotic volume decrease (AVD), is a ubiquitous characteristic of programmed cell death that is independent of the death stimulus and occurs in all examples of apoptosis. Here we distinguished two specific stages of AVD based on cell size and a unique early reversal of intracellular ions that occurs in response to activation of both intrinsic and extrinsic cell death signal pathways. The primary stage of AVD is characterized by an early exchange of the normal intracellular ion distribution for sodium from 12 to 113.6 mm and potassium from 139.5 to 30 mm. This early ionic reversal is associated with a 20-40% decrease in cell volume, externalization of phosphatidylserine, loss of mitochondrial membrane potential, and caspase activation and activity along with nuclear condensation that occurs independent of actin cytoskeleton disruption. Disruption of the actin cytoskeleton, however, prevents a secondary stage of AVD in apoptotic cells, characterized by a loss of both potassium and sodium that results in an 80-85% loss in cell volume, DNA degradation, and apoptotic body formation. Together these studies demonstrate that AVD occurs in two distinct stages with the earliest stage reflecting a cellular cationic gradient reversal.

  5. Multifactor-surface-tests of organic insulating materials in the early stage of degradation

    SciTech Connect

    Kloes, H.J.; Koenig, D.

    1996-12-31

    Ageing due to multifactor stresses of the surface of organic materials has to be divided into two different stages named early and late stage of ageing. While standardized tests such as the inclined plane test or the rotating wheel dip test aim at verifying only the performance of insulating materials in the late stage of ageing, growing interest of scientists recently focuses on the early stage of ageing, characterized by a loss of hydrophobicity and an increase of leakage current as well as the appearance of surface partial discharges. To assess the phenomena in the early stage of ageing several new test facilities and diagnostic tools have been developed and applied, such as the inverse climatic chamber generating continuous condensation, the cold fog chamber and the modified rotating wheel dip test arrangement. This paper presents some new test results of polymer resin materials achieved in above mentioned test facilities and enables a comparison and assessment of the efficiency and the advantages of relevant test procedures.

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

    DOE PAGES

    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 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. Morphological changes to early stage Taenia solium cysticerci following oxfendazole treatment.

    PubMed

    Liu, Yong-Jie; Li, Qing-Zhang; Hao, Yan-Hong

    2003-01-01

    The progressive morphological changes to early stage Taenia solium cysticerci following the treatment of pigs with a single therapeutic dose of oxfendazole (30 mg/kg), are described. On Day 1 after treatment, no obvious changes occurred in the general appearance of the larvae but alternations were seen by electron microscope, with an apparent reduction in the number of microtriches, and a complete disappearance of the tegument. Numerous granules were seen to have accumulated in the tegument cells. As treatment progressed, damage to the cysticerci was more serious and, by five days, all cysticerci were seen to be in an advanced stage of degeneration. By 45 days post-treatment, all cysts were calcified. These results suggest that oxfendazole is a highly effective drug against T. solium cysticerci in the early stages of development.

  8. Treatment of Early Stage Non-Small Cell Lung Cancer: Surgery or Stereotactic Ablative Radiotherapy?

    PubMed Central

    Uzel, Esengül Koçak; Abacıoğlu, Ufuk

    2015-01-01

    The management of early-stage Non-small Cell Lung Cancer (NSCLC) has improved recently due to advances in surgical and radiation modalities. Minimally-invasive procedures like Video-assisted thoracoscopic surgery (VATS) lobectomy decreases the morbidity of surgery, while the numerous methods of staging the mediastinum such as endobronchial and endoscopic ultrasound-guided biopsies are helping to achieve the objectives much more effectively. Stereotactic Ablative Radiotherapy (SABR) has become the frontrunner as the standard of care in medically inoperable early stage NSCLC patients, and has also been branded as tolerable and highly effective. Ongoing researches using SABR are continuously validating the optimal dosing and fractionation schemes, while at the same time instituting its role for both inoperable and operable patients. PMID:25759766

  9. 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.

  10. 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.

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

    PubMed

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

    2016-04-01

    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. PMID:26972797

  12. 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.

  13. Fate mapping of gallbladder progenitors in posteroventral foregut endoderm of mouse early somite-stage embryos.

    PubMed

    Uemura, Mami; Igarashi, Hitomi; Ozawa, Aisa; Tsunekawa, Naoki; Kurohmaru, Masamichi; Kanai-Azuma, Masami; Kanai, Yoshiakira

    2015-05-01

    In early embryogenesis, the posteroventral foregut endoderm gives rise to the budding endodermal organs including the liver, ventral pancreas and gallbladder during early somitogenesis. Despite the detailed fate maps of the liver and pancreatic progenitors in the mouse foregut endoderm, the exact location of the gallbladder progenitors remains unclear. In this study, we performed a DiI fate-mapping analysis using whole-embryo cultures of mouse early somite-stage embryos. Here, we show that the majority of gallbladder progenitors in 9-11-somite-stage embryos are located in the lateral-most domain of the foregut endoderm at the first intersomite junction level along the anteroposterior axis. This definition of their location highlights a novel entry point to understanding of the molecular mechanisms of initial specification of the gallbladder.

  14. 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.

  15. Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

    2014-01-01

    Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

  16. Complications of radical hysterectomy: clinical experience of 115 early stage cervical cancers.

    PubMed

    Zorlu, C G; Aydoğlu, T; Ergün, Y; Kuşçu, E; Cobanoğlu, O; Koçak, S

    1998-01-01

    We evaluated the clinical experience of 115 women with early stage cervical cancer who had been operated in our Gynecologic Oncology Clinic. Of these, 85 were in stage I, and 30 in stage II. Intraoperative complications occurred in 16 patients including 3 cases concerning bladder, 1 ureter, 1 aorta, 5 v.cava inferior, 1 internal iliac a., 3 internal iliac v., 1 obturator nerve and 1 rectovaginal septum hematoma formation. Postoperative complications were observed in 38 patients. These were 14 bladder dysfunctions, 10 lymphocyst formations, 6 urinary infections, 12 wound infections, 3 pelvic infections, 2 eviscerations and 1 incisional hernia. However, no death occurred due to intraoperative or postoperative complications. Pelvic lymph node metastases were observed in 32 patients of whom 17 had only unilateral involvement, most often in the obturator region. Para-aortic lymph node metastases were diagnosed in 4 patients, all of whom were in stage II.

  17. 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.

  18. 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.

  19. Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

    PubMed

    Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

    2011-01-01

    Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.

  20. Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

    PubMed

    Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

    2011-01-01

    Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base. PMID:21822050

  1. 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

  2. Optimization of a novel enzyme treatment process for early-stage processing of sheepskins.

    PubMed

    Lim, Y F; Bronlund, J E; Allsop, T F; Shilton, A N; Edmonds, R L

    2010-01-01

    An enzyme treatment process for early-stage processing of sheepskins has been previously reported by the Leather and Shoe Research Association of New Zealand (LASRA) as an alternative to current industry operations. The newly developed process had marked benefits over conventional processing in terms of a lowered energy usage (73%), processing time (47%) as well as water use (49%), but had been developed as a "proof of principle''. The objective of this work was to develop the process further to a stage ready for adoption by industry. Mass balancing was used to investigate potential modifications for the process based on the understanding developed from a detailed analysis of preliminary design trials. Results showed that a configuration utilising a 2 stage counter-current system for the washing stages and segregation and recycling of enzyme float prior to dilution in the neutralization stage was a significant improvement. Benefits over conventional processing include a reduction of residual TDS by 50% at the washing stages and 70% savings on water use overall. Benefits over the un-optimized LASRA process are reduction of solids in product after enzyme treatment and neutralization stages by 30%, additional water savings of 21%, as well as 10% savings of enzyme usage. PMID:20861557

  3. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

    PubMed Central

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

  4. 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.

  5. 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

  6. 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

  7. Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development

    PubMed Central

    POPKEN, Jens; SCHMID, Volker J.; STRAUSS, Axel; GUENGOER, Tuna; WOLF, Eckhard; ZAKHARTCHENKO, Valeri

    2015-01-01

    Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling

  8. 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.

  9. Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma.

    PubMed

    Reichl, Patrick; Fang, Meng; Starlinger, Patrick; Staufer, Katharina; Nenutil, Rudolf; Muller, Petr; Greplova, Kristina; Valik, Dalibor; Dooley, Steven; Brostjan, Christine; Gruenberger, Thomas; Shen, Jiayun; Man, Kwan; Trauner, Michael; Yu, Jun; Gao, Chun Fang; Mikulits, Wolfgang

    2015-07-15

    If diagnosed at early stages, patients with hepatocellular carcinoma (HCC) can receive curative therapies, whereas therapeutic options at later stages are very limited. Here, we addressed the potential of soluble Axl (sAxl) as a biomarker of early HCC by analyzing levels of sAxl in 311 HCC and 237 control serum samples from centers in Europe and China. Serum concentrations of sAxl were significantly increased in HCC (18.575 ng/mL) as compared to healthy (13.388 ng/mL) or cirrhotic (12.169 ng/mL) controls. Receiver operating characteristic curve analysis of sAxl in very early stage HCC patients (BCLC 0) showed an area under the curve (AUC) of 0.848, with a sensitivity of 76.9% and a specificity of 69.2%. α-Fetoprotein (AFP)-negative HCC patients displayed an AUC of 0.803, with sensitivity and specificity of 73% and 70.8%. Combination of sAxl and AFP improved diagnostic accuracy to 0.936 in very early HCC patients and to 0.937 in all HCC. Differential diagnosis of very early HCC versus liver cirrhosis showed a combined performance for sAxl and AFP of 0.901 with a sensitivity of 88.5% and a specificity of 76.7%. Furthermore, sAxl levels failed to be elevated in primary ovarian, colorectal and breast carcinomas as well as in secondary hepatic malignancies derived from colon. In summary, sAxl outperforms AFP in detecting very early HCC as compared to healthy or cirrhotic controls and shows high diagnostic accuracy for AFP-negative patients. sAxl is specific for HCC and suggested as a biomarker for routine clinical use.

  10. 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.

  11. Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

    PubMed Central

    Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

    2016-01-01

    Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

  12. Mitochondrial response to oxidative and nitrosative stress in early stages of diabetes.

    PubMed

    Noriega-Cisneros, Ruth; Cortés-Rojo, Christian; Manzo-Avalos, Salvador; Clemente-Guerrero, Mónica; Calderón-Cortés, Elizabeth; Salgado-Garciglia, Rafael; Montoya-Pérez, Rocío; Boldogh, Istvan; Saavedra-Molina, Alfredo

    2013-11-01

    Diabetes mellitus (DM) is associated with increased production of reactive oxygen and nitrogen species; consequently, an increase in lipid peroxidation and a decrease in antioxidants resulting in mitochondrial dysfunction. Using a rat model of DM induced by streptozotocin, we show the opposite: an increase in NO levels, S-nitrosylation, aconitase activity, and total glutathione and a decrease in lipid peroxidation at early stages of diabetes. These data imply that the decrease in lipid peroxidation is a vital early response to hyperglycemia to prevent escalation of ROS generation in mitochondria. These results also suggest a need for novel therapeutic targets to prevent the neurological consequences of diabetes.

  13. Prognostic modeling in early stage lung cancer: an evolving process from histopathology to genomics.

    PubMed

    Harpole, David H

    2007-05-01

    The goal is to validate a molecular-based tumor model that identifies patients at low-risk for cancer recurrence and who will not benefit from adjuvant chemotherapy. The remaining patients will be randomized to observation (present standard of care) or adjuvant chemotherapy to determine efficacy of adjuvant in this population. Investigators have focused on the identification of markers that may predict poor prognosis as a way to "enrich" the population by separating those likely to have early recurrence and cancer death from those not needing additional treatment after resection. The initial projects refined predictive models of cancer recurrence after resection for patients with early stage non-small cell lung cancer.

  14. Defective skeletogenesis and oversized otoliths in fish early stages in a changing ocean.

    PubMed

    Pimentel, Marta S; Faleiro, Filipa; Dionísio, Gisela; Repolho, Tiago; Pousão-Ferreira, Pedro; Machado, Jorge; Rosa, Rui

    2014-06-15

    Early life stages of many marine organisms are being challenged by rising seawater temperature and CO₂ concentrations, but their physiological responses to these environmental changes still remain unclear. In the present study, we show that future predictions of ocean warming (+4°C) and acidification (ΔpH=0.5 units) may compromise the development of early life stages of a highly commercial teleost fish, Solea senegalensis. Exposure to future conditions caused a decline in hatching success and larval survival. Growth, metabolic rates and thermal tolerance increased with temperature but decreased under acidified conditions. Hypercapnia and warming amplified the incidence of deformities by 31.5% (including severe deformities such as lordosis, scoliosis and kyphosis), while promoting the occurrence of oversized otoliths (109.3% increase). Smaller larvae with greater skeletal deformities and larger otoliths may face major ecophysiological challenges, which might potentiate substantial declines in adult fish populations, putting in jeopardy the species' fitness under a changing ocean.

  15. RNAs containing B2 repeated sequences are transcribed in the early stages of mouse embryogenesis.

    PubMed Central

    Vasseur, M; Condamine, H; Duprey, P

    1985-01-01

    An in situ hybridization technique was used to detect RNAs containing B2 sequences in the early mouse embryo. Accumulation of B2 sequences occurs early from the one cell stage. The level of B2 RNA decreases in the late two cell embryo, and then increases at the moment of second cleavage. In the blastocyst, inner cell mass cells contain more B2 transcripts than trophectoderm cells. In 7.5-day embryos the expression of B2 sequences is restricted to ectoderm and mesoderm. At all stages, transcription of the B2+ strand is greater than B2- strand. We detected B2+ RNAs in the nucleus and cytoplasm, whereas B2- RNAs were present only in the nucleus. Images Fig. 1. Fig. 2. Fig. 3. PMID:2411546

  16. Toxic effects of bisphenol A on early life stages of Japanese medaka (Oryzias latipes).

    PubMed

    Sun, Liwei; Lin, Xia; Jin, Rong; Peng, Tao; Peng, Zuhua; Fu, Zhengwei

    2014-08-01

    The toxic effects of bisphenol A (BPA) in aquatic organisms have attracted global attention. However, few studies have investigated its effects at the gene transcription level. In this study, we measured the transcriptional response of a set of genes associated with the hypothalamic-pituitary-gonadal axis following BPA exposure during the early life stage of Japanese medaka. Transcription of vitellogenin genes was induced in both sexes, indicating estrogenic disruption. However, changes in transcription of the steroid hormone receptor gene and steroidogenesis-regulating genes suggest that BPA also acts as an androgen receptor antagonist. BPA exposure also decreased the hatchability of medaka embryos and increased the growth of female larvae. These pronounced gender-specific effects observed in this study demonstrate that it is important to identify the sex of fish in the early life stage.

  17. Early stages of precipitation in Mg-RE alloys studied by positron annihilation spectroscopy

    NASA Astrophysics Data System (ADS)

    Vlček, M.; Čížek, J.; Melikhova, O.; Hruška, P.; Procházka, I.; Vlach, M.; Stulíková, I.; Smola, B.

    2016-01-01

    Magnesium alloys with rare earth (RE) elements are promising structural materials exhibiting favourable mechanical properties at elevated temperatures. However, the processes occurring during early stages of precipitation in these alloys are still not completely understood. In this work positron lifetime spectroscopy combined with coincidence Doppler broadening was employed for investigation of early stages of precipitation in Mg-RE alloys. Presence of quenched-in vacancy clusters was observed after solution treatment of studied alloys. These quenched-in vacancy clusters are bound to RE solutes and thereby stabilized at room temperature. During natural aging, RE clusters are formed by vacancy-assisted long-range diffusion. In addition, hardness of studied materials increases and quenched-in vacancy clusters are annealed out during the course of natural aging. Simple model was developed to describe hardening during natural aging.

  18. ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial Cancer.

    PubMed

    Wahl, Andrew O; Gaffney, David K; Jhingran, Anuja; Yashar, Catheryn M; Biagioli, Matthew; Elshaikh, Mohamed A; Jolly, Shruti; Kidd, Elizabeth; Lee, Larissa J; Li, Linna; Moore, David H; Rao, Gautam G; Williams, Ned L; Small, William

    2016-09-15

    These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer. PMID:27633412

  19. 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.

  20. The D-Optimality Item Selection Criterion in the Early Stage of CAT: A Study with the Graded Response Model

    ERIC Educational Resources Information Center

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

    2008-01-01

    During the early stage of computerized adaptive testing (CAT), item selection criteria based on Fisher"s information often produce less stable latent trait estimates than the Kullback-Leibler global information criterion. Robustness against early stage instability has been reported for the D-optimality criterion in a polytomous CAT with the…

  1. 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

    2015-07-01

    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.

  2. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson’s Disease

    PubMed Central

    Hacker, Mallory L.; Currie, Amanda D.; Molinari, Anna L.; Turchan, Maxim; Millan, Sarah M.; Heusinkveld, Lauren E.; Roach, Jonathon; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Byrne, Daniel W.; Charles, David

    2016-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD. PMID:26967937

  3. [Retraction of: Diagnostics and treatment of early stages of oral cancer].

    PubMed

    Warloe, Trond; Aamdal, Steinar; Reith, Albrecht; Bryne, Magne

    2006-09-01

    The undersigned, who are co-authors of the article Diagnostics and treatment of early stages of oral cancer, wish to retract it. The reason is that the basis for the review article has been shown to be false. A review committee, that has assessed the research activity of the main author, has concluded that the data in this article are fabricated. We can no longer stand behind the article and hereby retract it. PMID:16967079

  4. 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.

  5. Evaluation and treatment of high-risk patients with early-stage lung cancer.

    PubMed

    Mehta, Hiren J; Ross, Christopher; Silvestri, Gerard A; Decker, Roy H

    2011-12-01

    Standard therapy for early-stage non-small cell lung cancer is lobectomy for patients who are able to tolerate such surgery. However, the risk of postoperative morbidity is not trivial, with a 30% to 40% incidence of postoperative complications and a 1% to 5% incidence of operative mortality. Some patients, though technically resectable, refuse surgery or are considered medically inoperable because of insufficient respiratory reserve, cardiovascular disease, or general frailty. This group is considered either "high risk" or "medically inoperable."

  6. Polymorphism in rice amylases at an early stage of seed germination.

    PubMed

    Mitsunaga, S; Kawakami, O; Numata, T; Yamaguchi, J; Fukui, K; Mitsui, T

    2001-03-01

    A polymorphism in rice amylases at an early stage of seed germination is analyzed by zymogram. In non-glutinous cultivars of rice, alpha-amylase isozymes are mainly confirmed in germinating seeds. However, in glutinous cultivars, beta-amylase isozymes, which are not confirmed in nonglutinous cultivars, make up the major part of the total amylase activity and the expression of alpha-amylases are repressed. PMID:11330685

  7. 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. PMID:26260856

  8. 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.

  9. Ultrastructure of basement membranes in monkey and shark teeth at an early stage of development.

    PubMed

    Sawada, Takashi

    2003-12-01

    The basement membrane, which separates the inner enamel epithelium from the dental papilla in the early stages of tooth development, is known to play a significant role in odontogenesis. In this review article, this basement membrane was described in detail based on our recent findings with the use of high-resolution electron microscopy. Tooth germs of a monkey (Macaca fuscata) and a shark (Cephaloscyllium umbratile) were processed for thin-section observations. During the early stage of development, the basement membrane of the inner enamel (dental) epithelium was composed of a lamina lucida, lamina densa, and much wider lamina fibroreticularis. At higher magnification, the lamina densa in both species was made up of a fine network of cords, which are generally the main constituents of the basement membranes. In the monkey tooth, the lamina fibroreticularis was rich in fibrils, which were now characterized as basotubules, 10-nm-wide microfibril-like structures. The space between the basotubules was filled with a cord network that extended from the lamina densa. Dental papilla cell processes were inserted into the lamina fibroreticularis, and their surface was closely associated with numerous parallel basotubules via 1.5- to 3-nm-wide filaments. In the shark tooth during its early stage of development, the basotubules were absent in the lamina fibroreticularis and only narrow extensions, 60-90 nm wide and 1-2 microm long, of the cord network of the lamina densa were present. The dental papilla cells were immobilized by means of the binding of their processes to the extensions. These results indicate that basement membranes in both monkey and shark teeth at early stage of development are specialized for functions as anchoring and firm binding, which are essential for the successful differentiation of the odontoblasts.

  10. Therapeutic role of systematic lymphadenectomy in early-stage endometrial cancer: A systematic review

    PubMed Central

    LI, MEI-YI; HU, XIAO-XIA; ZHONG, JIAN-HONG; CHEN, LU-LU; LIN, YONG-XIU

    2016-01-01

    The purpose of the current review was to examine whether systematic lymphadenectomy is safe and effective for treating early-stage endometrial cancer. PubMed, Embase, the Cochrane Library and the China National Knowledge Infrastructure databases were systematically searched during April 2014 to identify studies comparing the use of systematic lymphadenectomy and no systematic lymphadenectomy in parallel for the treatment of early-stage endometrial cancer. A total of 13 eligible studies involving 51,155 patients were included in this review. The median overall survival (OS) rate at 5 years following lymphadenectomy was 90% (range, 73.1–98.3%) for patients undergoing the systematic procedure and 88.2% (range, 68–98.4%) for patients not undergoing the systematic procedure. For the two types of lymphadenectomy, OS has tended to improve over the last 20 years. The combined rate of disease-free and progression-free survival was higher in patients who underwent systematic lymphadenectomy, and the recurrence rate was lower. In particular, systematic lymphadenectomy was associated with markedly higher OS than the non-systematic procedure for patients with intermediate- and high-risk endometrial cancer when ≥11 lymph nodes were removed. Systematic lymphadenectomy demonstrates clinical benefit in patients with early-stage endometrial cancer and should thus be a standard treatment option. In conclusion, systematic lymphadenectomy leads to higher OS than no systematic lymphadenectomy in intermediate- and high-risk patients with early-stage endometrial cancer, particularly when the procedure removes ≥11 lymph nodes. PMID:27313706

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

    PubMed

    Duan, Qianqian; Yang, Xiaohong; Huang, Xianzhi

    2015-07-01

    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.

  12. Cryopreservation of In Vitro-Produced Early-Stage Porcine Embryos in a Closed System

    PubMed Central

    Men, Hongsheng; Spate, Lee D.; Murphy, Clifton N.; Prather, Randall S.

    2015-01-01

    Abstract Cryostorage of porcine embryos in a closed pathogen-free system is essential for the maintenance and safeguard of swine models. Previously, we reported a protocol for the successful cryopreservation of porcine embryos at the blastocyst stage in 0.25 mL ministraws. In this experiment, we aimed at developing a protocol to apply the same concept for the cryopreservation of early-stage porcine embryos. Porcine embryos from day 2 through day 4 were delipidated by using a modified two-step centrifugation method and were then cryopreserved in sealed 0.25 mL straws by using a slow cooling method. Control groups included open pulled straw (OPS) vitrified embryos after delipidation and noncryopreserved embryos without delipidation. There were no significant differences in cryosurvival between embryos frozen in 0.25 mL straws and OPS vitrified embryos across all the stages (two cell to morula) examined (p>0.05). Similarly, in all groups examined, the blastocyst rates were not different between the two cryopreserved groups. However, the blastocyst rates from the cryopreserved groups were significantly lower than the noncryopreserved controls (p<0.05). This experiment demonstrated that early-stage porcine embryos can survive cryopreservation in a closed system by using a slow cooling method at a comparable rate to those vitrified by using an ultrarapid cooling method (p>0.05). However, the developmental competence was significantly reduced after cryopreservation compared to noncryopreserved embryos. Further research is needed to optimize the protocol to improve the developmental potential of cryopreserved early-stage porcine embryos in sealed straws. PMID:26309801

  13. 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. PMID:25964662

  14. 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

  15. Ontogenetic development in the morphology and behavior of loach ( Misgurnus anguillicaudatus) during early life stages

    NASA Astrophysics Data System (ADS)

    Gao, Lei; Duan, Ming; Cheng, Fei; Xie, Songguang

    2014-09-01

    Loach ( Misgurnus anguillicaudatus) are a commercially important fish in China and an ideal aquaculture species. However, culturists experience high larval and juvenile mortality during mass production. To provide insight into ways to improve larviculture techniques, we describe the morphological characteristics and behavior of loach during the larval and early juvenile stages. Yolksac larvae ranged from 2.8 to 4.0 mm body length (BL) between days 0 to 4; preflexion larvae ranged from 3.6 to 5.5 mm BL between days 4 to 6; flexion larvae ranged from 4.8 to 8.1 mm BL between days 5 and 14; and postflexion larvae ranged from 7.1 to 15.7 mm BL between days 11 to 27; the minimum length and age of juveniles was 14.1 mm BL and 23 d, respectively. Loach are demersal from hatch through to the early juvenile stages. A suite of morphological characteristics (e.g., external gill filament and ventral mouth opening) and behavioral traits have developed to adapt to demersal living. We observed positive allometric growth in eye diameter, head length, head height, and pectoral fin length during the early larval stages, reflecting the priorities in the development of the organs essential for survival. Our results provide a basis for developing techniques to improve the survival of larval and juvenile loach during mass production.

  16. New features of triacylglycerol biosynthetic pathways of peanut seeds in early developmental stages.

    PubMed

    Yu, Mingli; Liu, Fengzhen; Zhu, Weiwei; Sun, Meihong; Liu, Jiang; Li, Xinzheng

    2015-11-01

    The peanut (Arachis hypogaea L.) is one of the three most important oil crops in the world due to its high average oil content (50 %). To reveal the biosynthetic pathways of seed oil in the early developmental stages of peanut pods with the goal of improving the oil quality, we presented a method combining deep sequencing analysis of the peanut pod transcriptome and quantitative real-time PCR (RT-PCR) verification of seed oil-related genes. From the sequencing data, approximately 1500 lipid metabolism-associated Unigenes were identified. The RT-PCR results quantified the different expression patterns of these triacylglycerol (TAG) synthesis-related genes in the early developmental stages of peanut pods. Based on these results and analysis, we proposed a novel construct of the metabolic pathways involved in the biosynthesis of TAG, including the Kennedy pathway, acyl-CoA-independent pathway and proposed monoacylglycerol pathway. It showed that the biosynthetic pathways of TAG in the early developmental stages of peanut pods were much more complicated than a simple, unidirectional, linear pathway.

  17. Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

    PubMed Central

    Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

    2016-01-01

    Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

  18. Fertility-Preserving Surgery in Patients with Early Stage Cervical Carcinoma

    PubMed Central

    Kardakis, Spyridon

    2012-01-01

    Fertility preservation is an important issue for patients in reproductive age with early stage cervical cancer. In view of recent developments, our purpose was to review and discuss available surgical alternatives. A literature search was conducted using PUBMED, including papers between 1980 and December 2011. In patients with stage IA1 cervical cancer, conization is a valid alternative. Patients with stage IA2-IB1 disease can be conservatively treated by radical trachelectomy. This is as well-established conservative approach and appears to be safe and effective in allowing a high chance of conception. Prematurity is the most serious issue in pregnancies following trachelectomy. Less invasive options such as simple trachelectomy or conization seem to be feasible for stages IA2-IB1, but more and better evidence is needed. Neoadjuvant therapy might allow conservative surgery to be performed also in patients with more extensive lesions. Ovarian transposition is important when adjuvant radiation is needed. In conclusion, available literature shows that there are interesting fertility-sparing treatment alternatives to the “golden standard” for the management of early cervical cancer in young women. PMID:23320192

  19. 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.

  20. Is Ovarian Preservation Feasible in Early-Stage Adenocarcinoma of the Cervix?

    PubMed Central

    Lu, Huaiwu; Li, Jing; Wang, Lijuan; Zhou, Hui; Liu, Yunyun; Wang, Dongyan; Lin, Zhongqiu

    2016-01-01

    Background In cervical adenocarcinoma, surgical treatment involves bilateral oophorectomy, which affects the long-term quality of life. The aim of our study was to access the incidence of ovarian metastasis in early-stage cervical adenocarcinoma and to suggest an algorithm for the triage of these patients to preserve the ovaries. Material/Methods A total 101 patients with cervical adenocarcinoma who had undergone radical hysterectomy with pelvic lymphadenectomy and bilateral oophorectomy were included in this study. Data on the clinicopathologic characteristics of the cases were collected and low risk factors for ovarian metastasis in early-stage cervical adenocarcinoma were analyzed. Results The ovary metastasis rate of cervical adenocarcinoma in this study was 4.95%, while it is only 2% in stage IB1. Pathological grade, LSVI, lymph node status, tumor size, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis, while LSVI, lymph node status, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis in stage IB. Multivariate analysis revealed that LVSI and lymph node metastasis were independent risk factors for ovarian metastasis in all stages of cervical adenocarcinoma, but involvement of the junction of the cervix and the body of the uterus was an independent risk factor for ovarian metastasis in stage IB. Conclusions The incidence of ovarian metastasis in cervical adenocarcinoma is low. Our study suggests that ovarian preservation is safe and feasible in patients with no risk factors for ovarian metastasis. Further prospective studies are warranted. PMID:26852916

  1. 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

  2. Operative link on gastritis assessment stage is an appropriate predictor of early gastric cancer

    PubMed Central

    Zhou, Ying; Li, Hai-Yan; Zhang, Jing-Jing; Chen, Xiao-Yu; Ge, Zhi-Zheng; Li, Xiao-Bo

    2016-01-01

    AIM: To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer. METHODS: A prospective study was conducted with 71 patients with early gastric cancer (EGC) and 156 patients with non-EGC. All patients underwent endoscopic examination and systematic biopsy. Outcome measures were assessed and compared, including the Japanese endoscopic gastric atrophy (EGA) classification method and the modified OLGA method as well as the modified OLGIM method. Helicobacter pylori (H. pylori) status was determined for all study participants. Stepwise logistic regression modeling was performed to analyze correlations between EGC and the EGA, OLGA and OLGIM methods. RESULTS: For patients with EGC and patients with non-EGC, the proportions of moderate-to-severe EGA cases were 64.8% and 44.9%, respectively (P = 0.005), the proportions of OLGA stages III-IV cases were 52.1% and 22.4%, respectively (P < 0.001), and the proportions of OLGIM stages III-IV cases were 42.3% and 19.9%, respectively (P < 0.001). OLGA stage and OLGIM stage were significantly related to EGA classification; specifically, logistic regression modeling showed significant correlations between EGC and moderate-to-severe EGA (OR = 1.95, 95% CI: 1.06-3.58, P = 0.031) and OLGA stages III-IV (OR = 3.14, 95%CI: 1.71-5.81, P < 0.001), but no significant correlation between EGC and OLGIM stages III-IV (P = 0.781). H. pylori infection rate was significantly higher in patients with moderate-to-severe EGA (75.0% vs 54.1%, P = 0.001) or OLGA/OLGIM stages III-IV (OLGA: 83.6% vs 55.8%, P < 0.001; OLGIM: 83.6% vs 57.8%, P < 0.001). CONCLUSION: OLGA classification is optimal for EGC screening. A surveillance program including OLGA stage and H. pylori infection status may facilitate early detection of gastric cancer. PMID:27053859

  3. Dynamic drying in the early-stage coalescence of droplets sitting on a plate

    NASA Astrophysics Data System (ADS)

    Narhe, R. D.; Beysens, D. A.; Pomeau, Y.

    2008-02-01

    The early-stage coalescence of two sessile drops is investigated theoretically and experimentally. The coalescence of small sessile drops of diethylene glycol on silicon wafer is induced either by condensation or syringe deposition. The bridge geometry in directions parallel and perpendicular to the substrate, the bridge contact angle and the direct fluid velocity are simultaneously analyzed. The process is characterized by the nucleation and growth of a bridge between the two drops. Three stages are identified. i) An initial stage of dynamic drying where the capillary number Ca>0.02 and the contact line does not move appreciably. The bridge does not wet the solid and its size grows as time t perpendicularly to the substrate and as t1/2 parallel to the substrate. ii) A late stage where the contact line starts to move and where the bridge relaxes exponentially, making eventually the composite drop to be ellipsis like. This stage is followed by iii) a very slow evolution limited by the contact line motion where the drop relaxes to a circular shape with a dynamics that is 6 to 7 orders larger than bulk hydrodynamics predicts.

  4. Presentation of underglycosylated mucin 1 in pancreatic adenocarcinoma (PDAC) at early stages

    PubMed Central

    Lo, Su-Tang; Pantazopouos, Pamela; Medarova, Zdravka; Moore, Anna

    2016-01-01

    Underglycosylated mucin 1 antigen (uMUC1) is a proven biomarker of cancer progression relevant to many malignancies including pancreatic ductal adenocarcinoma (PDAC). However, while ample evidence exists of the expression of total MUC1, little is known about the abundance of the underglycolsylated form of the antigen and its significance in disease progression. Such knowledge is important because the underglycosylated form of MUC1 is intimately linked to metastatic potential. Here, we investigated the expression uMUC1 at various stages of PDAC including pancreatic intraepithelial neoplasia (PanIN). Immunohistochemical analysis was performed on human tissue microarrays (TMAs) containing PDAC and PanIN using monoclonal antibody specific to uMUC1. uMUC1 expression was analyzed by a traditional pathological scoring system and using automatic imaging analysis software. Our results demonstrated low uMUC1 abundance in PanIN lesions and a transient increase in antigen availability in stage I PDAC, followed by decreased expression in later stages of the disease. An additional finding was that there was intermediate expression of uMUC1 in adjacent normal tissues from PDAC irrespective of the stage. These studies suggest the intriguing possibility that a pro-metastatic uMUC1 expression signature may appear at early stages of PDAC, providing an additional clue about the aggressive nature of pancreatic cancer. PMID:27725904

  5. Narrowband Ultraviolet B Phototherapy of Early Stage Mycosis Fungoides in Korean Patients

    PubMed Central

    Jang, Min Soo; Baek, Jae Woo; Park, Jong Bin; Kang, Dong Young; Kang, Jin Seuk; Suh, Kee Suck

    2011-01-01

    Background Narrowband UVB (NBUVB) is currently used to treat early mycosis fungoides (MF). There are a number of reports on the efficacy and safety of NBUVB in Caucasians, but little data is available for Asians. Objective This study was designed to evaluate the effectiveness and safety of NBUVB for early stage MF in Korean patients. Methods We enrolled 14 patients (12 men, 2 women; age range, 10~64 years) with clinically and histologically proven MF. Three patients were stage IA, and the others were stage IB. The patients received NBUVB phototherapy three times a week. The starting dose was 70% of the minimal erythema dose and was increased in 20 percent increments if the previous treatment did not cause erythema. Clinical response, total number of treatments, total cumulative dose, duration of remission and side effects were investigated. Results Eleven of 14 patients (78.6%) achieved complete remission within a mean of 15.36±5.71 weeks (range, 5~27 weeks), 31.0±7.4 treatments (range, 16~39 treatments) and a mean cumulative UVB dose of 31.31±12.16 J/cm2 (range, 11.4~46.8 J/cm2). Three of the 14 patients (21.4%) achieved a partial remission. After discontinuation of treatment, 6 of 11 patients (54.5%) with complete remission relapsed after a mean of 8.5±4.09 months. No serious adverse effects were observed except for hyperpigmentation (7/14, 50%). Conclusion Our data suggest that NBUVB therapy is safe and effective for the treatment of early stage MF in Korean patients. PMID:22148015

  6. 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

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

    PubMed

    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

  8. 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

  9. Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

    PubMed Central

    Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

    2015-01-01

    Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

  10. Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

    2012-01-01

    Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

  11. 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…

  12. 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.

  13. Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

    PubMed Central

    Meyerson, Nicholas R.; Sharma, Amit; Wilkerson, Gregory K.

    2015-01-01

    ABSTRACT Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCE Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Early-stage comparative sustainability assessment of new bio-based processes.

    PubMed

    Patel, Akshay D; Meesters, Koen; den Uil, Herman; de Jong, Ed; Worrell, Ernst; Patel, Martin K

    2013-09-01

    Our increasing demand for materials and energy has put critical roadblocks on our path towards a sustainable society. To remove these roadblocks, it is important to engage in smart research and development (R&D). We present an early-stage sustainability assessment framework that is used to analyze eight new bio-based process alternatives developed within the CatchBio research consortium in the Netherlands. This assessment relies on a multi-criteria approach, integrating the performance of chemical conversions based on five indicators into an index value. These indicators encompass economics, environmental impact, hazards and risks thereby incorporating elements of green chemistry principles, and techno-economic and life cycle assessments. The analyzed bio-based options target the production of fuels and chemicals through chemical catalysis. For each bio-based process, two R&D stages (current laboratory and expected future) are assessed against a comparable conventional process. The multi-criteria assessment in combination with the uncertainty and scenario analysis shows that the chemical production processes using biomass as feedstock can provide potential sustainability benefits over conventional alternatives. However, further development is necessary to realize the potential benefits from biomass gasification and pyrolysis processes for fuel production. This early stage assessment is intended as an input for R&D decision making to support optimal allocation and utilization of resources to further develop promising bio-based processes. PMID:24078179

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

    2014-02-01

    The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

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

    PubMed Central

    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. PMID:27045806

  5. Muscle fiber conduction velocity in different gait phases of early and late-stage diabetic neuropathy.

    PubMed

    Suda, Eneida Yuri; Gomes, Aline A; Butugan, Marco Kenji; Sacco, Isabel C N

    2016-10-01

    We investigated the muscle fiber conduction velocity (MFCV) during gait phases of the lower limb muscles in individuals with various degrees of diabetic peripheral neuropathy (DPN). Forty-five patients were classified into severity degrees of DPN by a fuzzy model. The stages were absent (n=11), mild (n=14), moderate (n=11) and severe (n=9), with 10 matched healthy controls. While walking, all subjects had their sEMG (4 linear electrode arrays) recorded for tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL) and biceps femoris (BF). MFCV was calculated using a maximum likelihood algorithm with 30ms standard deviation Gaussian windows. In general, individuals in the earlier stages of DPN showed lower MFCV of TA, GM and BF, whilst individuals with severe DPN presented higher MFCV of the same muscles. We observed that mild patients already showed lower MFCV of TA at early stance and swing, and lower MFCV of BF at swing. All diabetic groups showed a markedly reduction in MFCV of VL, irrespective of DPN. Severe patients presented higher MFCV mainly in distal muscles, TA at early and swing phases and GM at propulsion and midstance. The absent group already showed MFCV of VL and GM reductions at the propulsion phase and of VL at early stance. Although MFCV changes were not as progressive as the DPN was, we clearly distinguished diabetic patients from controls, and severe patients from all others.

  6. 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.

  7. Role of subchondral bone during early-stage experimental TMJ osteoarthritis.

    PubMed

    Embree, M; Ono, M; Kilts, T; Walker, D; Langguth, J; Mao, J; Bi, Y; Barth, J L; Young, M

    2011-11-01

    Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease that affects both cartilage and subchondral bone. We used microarray to identify changes in gene expression levels in the TMJ during early stages of the disease, using an established TMJ OA genetic mouse model deficient in 2 extracellular matrix proteins, biglycan and fibromodulin (bgn(-/0)fmod(-/-)). Differential gene expression analysis was performed with RNA extracted from 3-week-old WT and bgn(-/0)fmod(-/-) TMJs with an intact cartilage/subchondral bone interface. In total, 22 genes were differentially expressed in bgn(-/0)fmod(-/-) TMJs, including 5 genes involved in osteoclast activity/differentiation. The number of TRAP-positive cells were three-fold higher in bgn(-/0)fmod(-/-) TMJs than in WT. Quantitative RT-PCR showed up-regulation of RANKL and OPG, with a 128% increase in RANKL/OPG ratio in bgn(-/0)fmod(-/-) TMJs. Histology and immunohistochemistry revealed tissue disorganization and reduced type I collagen in bgn(-/0)fmod(-/-) TMJ subchondral bone. Early changes in gene expression and tissue defects in young bgn(-/0)fmod(-/-) TMJ subchondral bone are likely attributed to increased osteoclast activity. Analysis of these data shows that biglycan and fibromodulin are critical for TMJ subchondral bone integrity and reveal a potential role for TMJ subchondral bone turnover during the initial early stages of TMJ OA disease in this model. PMID:21917603

  8. Role of Subchondral Bone during Early-stage Experimental TMJ Osteoarthritis

    PubMed Central

    Embree, M.; Ono, M.; Kilts, T.; Walker, D.; Langguth, J.; Mao, J.; Bi, Y.; Barth, J.L.; Young, M.

    2011-01-01

    Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease that affects both cartilage and subchondral bone. We used microarray to identify changes in gene expression levels in the TMJ during early stages of the disease, using an established TMJ OA genetic mouse model deficient in 2 extracellular matrix proteins, biglycan and fibromodulin (bgn-/0fmod-/-). Differential gene expression analysis was performed with RNA extracted from 3-week-old WT and bgn-/0fmod-/- TMJs with an intact cartilage/subchondral bone interface. In total, 22 genes were differentially expressed in bgn-/0fmod-/- TMJs, including 5 genes involved in osteoclast activity/differentiation. The number of TRAP-positive cells were three-fold higher in bgn-/0fmod-/- TMJs than in WT. Quantitative RT-PCR showed up-regulation of RANKL and OPG, with a 128% increase in RANKL/OPG ratio in bgn-/0fmod-/- TMJs. Histology and immunohistochemistry revealed tissue disorganization and reduced type I collagen in bgn-/0fmod-/- TMJ subchondral bone. Early changes in gene expression and tissue defects in young bgn-/0fmod-/- TMJ subchondral bone are likely attributed to increased osteoclast activity. Analysis of these data shows that biglycan and fibromodulin are critical for TMJ subchondral bone integrity and reveal a potential role for TMJ subchondral bone turnover during the initial early stages of TMJ OA disease in this model. PMID:21917603

  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. Proteomic analysis of liver tissue from HBx-transgenic mice at early stages of hepatocarcinogenesis.

    PubMed

    Kim, Sun-Young; Lee, Phil Young; Shin, Hye-Jun; Kim, Do Hyung; Kang, Sunghyun; Moon, Hyung-Bae; Kang, Sang Won; Kim, Jin-Man; Park, Sung Goo; Park, Byoung Chul; Yu, Dae-Yeul; Bae, Kwang-Hee; Lee, Sang Chul

    2009-11-01

    The hepatitis B virus X-protein (HBx), a multifunctional viral regulator, participates in the viral life cycle and in the development of hepatocellular carcinoma (HCC). We previously reported a high incidence of HCC in transgenic mice expressing HBx. In this study, proteomic analysis was performed to identify proteins that may be involved in hepatocarcinogenesis and/or that could be utilized as early detection biomarkers for HCC. Proteins from the liver tissue of HBx-transgenic mice at early stages of carcinogenesis (dysplasia and hepatocellular adenoma) were separated by 2-DE, and quantitative changes were analyzed. A total of 22 spots displaying significant quantitative changes were identified using LC-MS/MS. In particular, several proteins involved in glucose and fatty acid metabolism, such as mitochondrial 3-ketoacyl-CoA thiolase, intestinal fatty acid-binding protein 2 and cytoplasmic malate dehydrogenase, were differentially expressed, implying that significant metabolic alterations occurred during the early stages of hepatocarcinogenesis. The results of this proteomic analysis provide insights into the mechanism of HBx-mediated hepatocarcinogenesis. Additionally, this study identifies possible therapeutic targets for HCC diagnosis and novel drug development for treatment of the disease.

  12. Muscle fiber conduction velocity in different gait phases of early and late-stage diabetic neuropathy.

    PubMed

    Suda, Eneida Yuri; Gomes, Aline A; Butugan, Marco Kenji; Sacco, Isabel C N

    2016-10-01

    We investigated the muscle fiber conduction velocity (MFCV) during gait phases of the lower limb muscles in individuals with various degrees of diabetic peripheral neuropathy (DPN). Forty-five patients were classified into severity degrees of DPN by a fuzzy model. The stages were absent (n=11), mild (n=14), moderate (n=11) and severe (n=9), with 10 matched healthy controls. While walking, all subjects had their sEMG (4 linear electrode arrays) recorded for tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL) and biceps femoris (BF). MFCV was calculated using a maximum likelihood algorithm with 30ms standard deviation Gaussian windows. In general, individuals in the earlier stages of DPN showed lower MFCV of TA, GM and BF, whilst individuals with severe DPN presented higher MFCV of the same muscles. We observed that mild patients already showed lower MFCV of TA at early stance and swing, and lower MFCV of BF at swing. All diabetic groups showed a markedly reduction in MFCV of VL, irrespective of DPN. Severe patients presented higher MFCV mainly in distal muscles, TA at early and swing phases and GM at propulsion and midstance. The absent group already showed MFCV of VL and GM reductions at the propulsion phase and of VL at early stance. Although MFCV changes were not as progressive as the DPN was, we clearly distinguished diabetic patients from controls, and severe patients from all others. PMID:27567140

  13. [Early Stages of Skull Embryogenesis in the Grass Snake, Natrix natrix (Serpentes, Colubridae)].

    PubMed

    Kovtun, M F; Sheverdyukova, H V

    2015-01-01

    Studies of previous authors on snake skull embryogenesis have been performed on embryos obtained from eggs after oviposition. The aim of this study was to investigate the initial stages of chondrocranium development in Grass-snake Natrixnatrix Linnaeus, 1758, embryos before oviposition. Natrix natrix embryos at early developmental stages (24-27 according to the table of normal development by D. Zehr (1962)) were obtained by means of caesarean section. At developmental stages 25-27, previously undescribed structures were found in the region of future skull formation. These structures exist during one or two stages and then disappear. Therefore, we call them "temporary structures." The assumption about the nature of these structures is based on their topography and comparison with the structures of developing or fully formed chondrocranium in other vertebrates. It is hypothesized that the temporary structures in Natrix natrix chondrocranium are vestiges ofprimary chondrocranium of ancestral vertebrate forms, and they indicate the existence of several variants in the formation of chondrocranium in the historical vertebrates.' development.

  14. Supradiaphragmatic early stage Hodgkin's disease: does mantle radiation therapy still have a role?

    PubMed

    Frezza, G; Barbieri, E; Zinzani, P L; Babini, L; Tura, S

    1996-01-01

    Extended field radiation therapy represents the main therapeutic option in early stage Hodgkin's disease with favorable prognostic features. Its role however has recently been criticized, mainly due to the high incidence of late complications in irradiated tissues. Furthermore, surgical staging, which in the opinion of many is mandatory for proper selection of patients for radiotherapy alone, has a well-known morbidity, and splenectomy has been associated with a high risk of secondary leukemias. Lastly, the failure rate after radiotherapy only is not negligible and second-line treatment is not always successful. A review of our experience and of the recent literature has allowed us to refute these objections. The results of radiotherapy, when properly performed, are highly reliable and have been reproducible in many Institutions. Chemotherapy alone cannot yet be regarded as an alternative to radiotherapy in these patients since data reported on this issue are conflicting. Present knowledge regarding the relationship between clinical features and the risk of occult subdiaphragmatic spread allows patients with localized disease to be selected without surgical staging; the results of radiotherapy in clinically staged patients confirm this statement. Concern for the late effects in irradiated tissues is justified, and future efforts should be directed at reducing the toxicity of this treatment. Associating a short chemotherapy course with low-dose radiotherapy to involved sites could help to achieve this goal.

  15. Supradiaphragmatic early stage Hodgkin's disease: does mantle radiation therapy still have a role?

    PubMed

    Frezza, G; Barbieri, E; Zinzani, P L; Babini, L; Tura, S

    1996-01-01

    Extended field radiation therapy represents the main therapeutic option in early stage Hodgkin's disease with favorable prognostic features. Its role however has recently been criticized, mainly due to the high incidence of late complications in irradiated tissues. Furthermore, surgical staging, which in the opinion of many is mandatory for proper selection of patients for radiotherapy alone, has a well-known morbidity, and splenectomy has been associated with a high risk of secondary leukemias. Lastly, the failure rate after radiotherapy only is not negligible and second-line treatment is not always successful. A review of our experience and of the recent literature has allowed us to refute these objections. The results of radiotherapy, when properly performed, are highly reliable and have been reproducible in many Institutions. Chemotherapy alone cannot yet be regarded as an alternative to radiotherapy in these patients since data reported on this issue are conflicting. Present knowledge regarding the relationship between clinical features and the risk of occult subdiaphragmatic spread allows patients with localized disease to be selected without surgical staging; the results of radiotherapy in clinically staged patients confirm this statement. Concern for the late effects in irradiated tissues is justified, and future efforts should be directed at reducing the toxicity of this treatment. Associating a short chemotherapy course with low-dose radiotherapy to involved sites could help to achieve this goal. PMID:8641642

  16. 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.

  17. Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients.

    PubMed

    Everaus, H; Lehtmaa, J; Luik, E; Kŏdar, H

    1992-11-01

    Fifty-six previously untreated stage-I (according to Rai) chronic lymphocytic leukemia (CLL) patients were examined for their clinical data, immunological characteristics, and hormonal values. Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), pisum sativatum agglutinin (PSA), wheat germ agglutinin (WGA), recombinant interleukin 2 (IL 2), and dextran sulfate (DxS); also by decreased immunoglobulin levels (IgG, IgA, IgE) and increased beta 2-microglobulin (beta 2-M) values. Simultaneously, dysregulation of the hypothalamic-pituitary-adrenal axis, immune system integration, imbalance of sex hormones, and changes in thyroid hormones were observed in the same group of patients. Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy.

  18. Blood rheology and platelet function in untreated early-stage essential hypertensives complicated with metabolic syndrome.

    PubMed

    Sugimori, Hiroko; Tomoda, Fumihiro; Koike, Tsutomu; Kinuno, Hiroyuki; Kurosaki, Hiroko; Masutani, Toshitaka; Inoue, Hiroshi

    2012-01-01

    We examined whether hemorheology and platelet function are affected in essential hypertensives (EHTs) of the World Health Organization stage I when complicated with metabolic syndrome (Mets). In 156 untreated EHTs, blood viscosity and platelet surface markers were determined. Blood viscosity was significantly elevated in 54 subjects with Mets compared with 102 subjects without Mets. Hematocrit and plasma viscosity increased in the group with Mets, although red blood cell rigidity index "k" did not differ between groups. As a whole group, blood viscosity correlated positively with hematocrit and plasma viscosity. Additionally, plasma viscosity correlated positively with plasma leptin, triglyceride, homeostasis model assessment index, C-reactive protein, and plasma fibrinogen, but negatively with high-density lipoprotein cholesterol. In contrast, no differences were seen in platelet surface markers between groups. In conclusion, EHTs of the early stage complicated with Mets are characterized by increased blood viscosity due to hemoconcentration and increased plasma viscosity. PMID:22570768

  19. Toxicity of tributyltin and triphenyltin to early life-stages of Paracentrotus lividus (Echinodermata: Echinoidea).

    PubMed

    Novelli, Alessandra Arizzi; Argese, Emanuele; Tagliapietra, Davide; Bettiol, Cinzia; Ghirardini, Annamaria Volpi

    2002-04-01

    Sperm cell and embryo toxicity tests using the Mediterranean sea urchin Paracentrotus lividus were performed to assess the toxicity of tributyltin chloride, bis(tributyltin)oxide, triphenyltin acetate, and triphenyltin hydroxide. Toxicity values (mean effective concentration [EC50]) ranged from 2.97 to 18.5 microg/L for sperm cells and from 1.11 to 2.62 microg/L for embryos. For sperm cells, the toxicity of the two tributyl compounds was significantly greater than that of two triphenyl compounds; for embryos, the triphenyl compounds appeared to be more toxic. Study of embryotoxic effects highlighted closely concentration-dependent damages, the most sensitive stages corresponding to the crucial phases of differentiation (gastrula and prisma). Both EC50 and no-observed-effect concentration values for the four organotin compounds are similar to those reported in the literature for early life stages of other marine organisms. PMID:11951962

  20. Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients.

    PubMed

    Everaus, H; Lehtmaa, J; Luik, E; Kŏdar, H

    1992-11-01

    Fifty-six previously untreated stage-I (according to Rai) chronic lymphocytic leukemia (CLL) patients were examined for their clinical data, immunological characteristics, and hormonal values. Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), pisum sativatum agglutinin (PSA), wheat germ agglutinin (WGA), recombinant interleukin 2 (IL 2), and dextran sulfate (DxS); also by decreased immunoglobulin levels (IgG, IgA, IgE) and increased beta 2-microglobulin (beta 2-M) values. Simultaneously, dysregulation of the hypothalamic-pituitary-adrenal axis, immune system integration, imbalance of sex hormones, and changes in thyroid hormones were observed in the same group of patients. Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy. PMID:1457579

  1. Early-stage precipitation in Al-Zn-Mg-Cu alloy (7050)

    SciTech Connect

    Sha Gang; Cerezo, Alfred

    2004-09-06

    GP zone and metastable {eta}{sup '} formation during the early-stage precipitation of a 7050 Al alloy aged at 121 deg. C has been investigated using transmission electron microscopy, together with 3-dimensional atom probe analysis (of the chemistry and morphology) of individual precipitates. Small Mg-rich clusters (GPI zones) are found in the alloy after short ageing times at 121 deg. C, together with larger GPI zones (Zn/Mg=1.0). Zn-rich {eta}{sup '} platelets are seen to form mainly between 30 and 240 min ageing, coexisting with larger GPI zones. A significant fraction of <1 1 0> elongated clusters have also been observed over this period of ageing. The dominant mechanism for {eta}{sup '} formation at this stage is shown to be by transformation of small GPI zones, via these elongated clusters and not by nucleation on larger zones.

  2. Toxicity of tributyltin and triphenyltin to early life-stages of Paracentrotus lividus (Echinodermata: Echinoidea).

    PubMed

    Novelli, Alessandra Arizzi; Argese, Emanuele; Tagliapietra, Davide; Bettiol, Cinzia; Ghirardini, Annamaria Volpi

    2002-04-01

    Sperm cell and embryo toxicity tests using the Mediterranean sea urchin Paracentrotus lividus were performed to assess the toxicity of tributyltin chloride, bis(tributyltin)oxide, triphenyltin acetate, and triphenyltin hydroxide. Toxicity values (mean effective concentration [EC50]) ranged from 2.97 to 18.5 microg/L for sperm cells and from 1.11 to 2.62 microg/L for embryos. For sperm cells, the toxicity of the two tributyl compounds was significantly greater than that of two triphenyl compounds; for embryos, the triphenyl compounds appeared to be more toxic. Study of embryotoxic effects highlighted closely concentration-dependent damages, the most sensitive stages corresponding to the crucial phases of differentiation (gastrula and prisma). Both EC50 and no-observed-effect concentration values for the four organotin compounds are similar to those reported in the literature for early life stages of other marine organisms.

  3. Symptomatic Lymphocele Formation After Sentinel Lymph Node Biopsy for Early Stage Cervical Cancer.

    PubMed

    Dogan, Nasuh Utku; Garagozova, Nigar; Pfiffer, Tatiana; Beier, Anna; Köhler, Christhardt; Favero, Giovanni

    2016-01-01

    In early stage cervical cancer, nodal status is the most important prognostic factor, and execution of retroperitoneal lymphadenectomy is currently an integral part of surgical therapy. Sentinel lymph node biopsy has been progressively incorporated with surgical therapy and could reduce morbidity. However, the current incidence of complications exclusively related to the procedure is unknown. We report on a 29-year-old woman affected by cervical cancer (Fédération Internationale de Gynécologie et d'Obstétrique Stage 1b1), who underwent sentinel lymph node biopsy in combination with radical vaginal trachelectomy, and who later developed a symptomatic pelvic lymphocele that required surgical therapy. Conservative procedures in the pelvic lymph nodes are not free of complications, especially with regard to the formation of symptomatic lymphoceles. This report brings to light an important discussion about the exact magnitude of the complications associated with the procedure.

  4. [Retrospective analysis for 104 cases of early-stage Hodgkin's Lymphoma treated with different modality therapies].

    PubMed

    Du, Ting-Ting; Xiao, Xiu-Bin; Su, Hang; Da, Yong; Chen, Xin-Lin; Zhong, Kai-Li; Zhao, Shi-Hua; Lu, Yun; Wang, Shuang; Zhang, Wei-Jing

    2012-04-01

    This paper explored the curative effect of combined modality therapy and extended field radiotherapy for early-stage Hodgkin's Lymphoma. 104 cases of early-stage Hodgkin's Lymphoma from Jan 1987 to Dec 2010 in PLA Hospital 307 were retrospectively analyzed, including 76 cases in combined modality therapy group and 28 cases in extended field radiotherapy group, and the long-term efficacy and toxicity of two therapy modalities were evaluated. The results showed that the median survival time of 104 cases was 85.42 months, the complete remission rates of combined modality therapy and extended field radiotherapy groups were 72.4 and 71.4 respectively (P = 0.924); the overall response rates of combined modality therapy and extended field radiotherapy groups were 97.4 and 96.4 respectively (P = 0.779); the 5-year overall survival (OS) rates in the 2 groups were 89.5 and 89.1 respectively, and the 8-year OS rates of the 2 groups were 81.3 and 70.6. No statistical difference was found in above-mentioned 2 groups. Moreover, the 5-year progression free survival (PFS) rates of these 2 groups were 84.2 and 69.0 (P = 0.04), and 8-year PFS rates of these 2 groups were 80.0 and 55.5 (P = 0.04) respectively, the 5-year relapse rates of these 2 groups were 28.1 and 45.6 (P = 0.023) respectively. It is concluded that the combined modality therapy can raise the PFS rate and reduce the relapse rate as compared with extended field radiotherapy for early-stage Hodgkin's Lymphoma, but there is no difference in the overall survival rate between the 2 groups.

  5. 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.

  6. Novel approaches to improve prostate cancer diagnosis and management in early-stage disease.

    PubMed

    Marberger, Michael; Barentsz, Jelle; Emberton, Mark; Hugosson, Jonas; Loeb, Stacy; Klotz, Laurence; Koch, Michael; Shariat, Shahrokh F; Vickers, Andrew

    2012-03-01

    The reported incidence of prostate cancer has risen since the implementation of screening. It is felt that the introduction of widespread prostate-specific antigen testing is responsible for most patients with prostate cancer now being diagnosed with asymptomatic, clinically localised disease. Diagnosis at this stage is associated with significantly improved treatment outcomes and longer life expectancy. Although there is evidence that screening has reduced prostate cancer mortality, there is a risk of over-diagnosis and over-treatment of early state prostate cancers, including clinically insignificant and indolent cancers. Active surveillance and focal therapy have been advocated as potential management options for some patients. However, these approaches face several challenges. Biopsy sampling errors together with less than optimal imaging of tumours can lead to difficulties in selecting suitable low-risk patients for these options.  To overcome these challenges, novel approaches to the staging and monitoring of patients with early prostate cancer are being developed. These include new imaging techniques, such as multi-parametric magnetic resonance imaging, and the development of new biomarkers and biopsy-based methods. These techniques aim to assess the potential of a specific tumour to be aggressive, and to improve patient outcomes. The aim of the present paper is to summarise presentations and debates at the third annual Interactive Genitourinary Cancer Conference concerning the use of population-based screening methods and the roles of active surveillance and focal therapy as prostate cancer treatments. The application of novel imaging biopsy-based methods and biomarkers in early-stage prostate cancer will also be explored.

  7. Prediction of motor outcome by shoulder subluxation at early stage of stroke

    PubMed Central

    Jang, Sung Ho; Yi, Ji Hyun; Chang, Chul Hoon; Jung, Young Jin; Kim, Seong Ho; Lee, Jun; Seo, Jeong Pyo

    2016-01-01

    Abstract We attempted to determine whether shoulder subluxation at the early stage of stroke can predict motor outcome in relation to the corticospinal tract (CST) state on diffusion tensor tractography. Fifty-nine stroke patients with severe hemiparesis were recruited. The patients were classified according to the distance of shoulder subluxation (group A: ≥2 cm, group B: <2 cm) and the affected CST on diffusion tensor tractography at the first evaluation (CST type A—the CST was discontinued at the stroke lesion; CST type B—the integrity of the CST was preserved). Motor function of the patients was evaluated twice (first: beginning of rehabilitation—24.1 ± 16.6 days; second: discharge after first rehabilitation—58.5 ± 24.1 days) using the Medical Research Council score, Motricity Index, and Modified Brunnstrom Classification. Regarding the improvement of the Medical Research Council for the finger extensor and upper Motricity Index, the order in terms of better recovery was as follows: group B–type B, group A–type B, group B–type A, and group A–type A (P < 0.05). The distance of shoulder subluxation showed significant correlation with improvement of the finger extensor (moderate negative correlation, r = −0.37) and improvement of the Modified Brunnstrom Classification (weak negative correlation, r = −0.29) (P < 0.05). The presence of shoulder subluxation at the early stage of stroke can be a predictor of motor outcome of the affected upper extremity and the degree of shoulder subluxation can be a predictor of the motor function of the affected hand. Therefore, our results suggest that shoulder subluxation in relation to the affected CST state at the early stage of stroke can be a prognostic factor for motor outcome. PMID:27512873

  8. Impact of diabetes mellitus on oncological outcomes after radical hysterectomy for early stage cervical cancer

    PubMed Central

    2016-01-01

    Objective To evaluate the relationship between type 2 diabetes mellitus (DM) and oncological outcomes in early stage cervical cancer patients who underwent radical surgical resection. Methods Patients with early stage cervical cancer diagnosed between 2001 and 2014 were retrospectively enrolled. We assessed the outcomes of 402 non-DM and 42 DM patients with cervical cancer. We tested the prognostic value of DM via Cox proportional hazard modeling. Results Patients with DM were more likely to be older and overweight. In the DM group, 20 and 22 patients were and were not taking metformin, respectively. The 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) rate for the whole study population were 88.49% and 96.34%, respectively. In the DM group, there was no evidence that metformin affected the RFS (p=0.553) or the OS (p=0.429). In multivariate analysis, age (p=0.007), histology (p=0.006), and deep stromal invasion (p=0.007) were independent adverse prognostic factors for RFS. There was a borderline significant association of increased RFS with DM (p=0.051). However, a time-varying-effect Cox model revealed that the DM was associated with a worse RFS (hazard ratio, 11.15; 95% CI, 2.00 to 62.08, p=0.022) after 5 years. DM (p=0.008), age (p=0.009), and node status (p=0.001) were the only 3 independent prognostic factors for OS. Conclusion Early stage cervical cancer patients with type 2 DM have a poorer oncological outcome than patients without DM. PMID:27029749

  9. 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.

  10. Qualitative evaluation of a self-management intervention for people in the early stage of dementia.

    PubMed

    Martin, Faith; Turner, Andrew; Wallace, Louise M; Stanley, Damian; Jesuthasan, Jana; Bradbury, Nicola

    2015-07-01

    Self-management programs are effective for people living with chronic illnesses. However, there has been little research addressing self-management for people with dementia in the early stages. This study presents a qualitative evaluation of the experiences of attending a novel self-management program and initial process evaluation. The program was designed with and for people with dementia. It addresses: (a) relationship with family, (b) maintenance of an active lifestyle, (c) psychological well-being, (d) techniques to cope with memory changes and (e) information about dementia. Six participants with early stage dementia completed the intervention that was co-delivered by lay and clinical professional tutors. Participants and tutors attended focus group and interviews at the end of the program to explore their perceptions of the intervention. These were audio-recorded, transcribed verbatim and analysed thematically. Participants reported enjoyment and benefits from the intervention. This was despite some reporting concerns relating to their memory difficulties. The program's flexible nature, focus on strengths and the opportunity to spend time with other people living with dementia were particularly well received. Participants and tutors outlined areas for further improvement. The program was feasible and its flexible delivery appeared to facilitate participant benefit. Emphasis should be placed on maintaining activity and relationships, improving positive well-being and social interaction during the program. Memory of the pleasant experience and strengths focus was evidenced, which may impact positively on quality of life. The results highlight the usefulness and acceptability of self-management for people with early stage dementia and provide initial support for the program's structure and content.

  11. 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.

  12. Prognostic significance of circulating laminin gamma2 for early-stage non-small-cell lung cancer

    PubMed Central

    Teng, Yu; Wang, Zitong; Ma, Li; Zhang, Lina; Guo, Yinan; Gu, Meng; Wang, Ziyu; Wang, Yue; Yue, Wentao

    2016-01-01

    Background Laminin gamma2 (Ln-γ2) chain, a distinctive subunit of heterotrimeric laminin-332, is frequently upregulated in carcinomas and is of great importance in cell migration and invasion. Despite this, the status of circulating Ln-γ2 in lung cancer patients is still uncertain. Patients and methods In this retrospective study, serum samples from 538 all-stage (stages I–IV) patients with non-small-cell lung cancer (NSCLC) and 94 age-matched healthy volunteers were investigated by enzyme-linked immunosorbent assay. Data were statistically analyzed in combination with clinicopathological information. Results Circulating Ln-γ2 was markedly increased in NSCLC, even in stage I cases (P<0.01), reflecting the progression of lung cancer. Survival analysis on 370 eligible patients indicated that serum Ln-γ2-negative patients survived much longer compared with Ln-γ2-positive individuals (P=0.028), and it was especially the case for stage I (P<0.001), stage T1 (P=0.001), and stage N0 patients (P=0.038), all of whom represented early-stage cases. For the advanced patients, however, overall survivals were not significantly different among stages II–IV (P=0.830), stages T2–T4 (P=0.575), stages N1–N3 (P=0.669), and stage M1 (P=0.849). Cox analysis subsequently defined serum Ln-γ2 as an independent prognostic indicator of NSCLC, particularly for early-stage patients. Furthermore, we demonstrated the association of serum Ln-γ2 with smoking behavior, but its association with tumor progression and early prognostic significance were not altered in the nonsmoking cohort. Conclusion Our study demonstrated that elevation of circulating Ln-γ2 was an early-emerging event in NSCLC and was significantly associated with poor prognosis in NSCLC, especially for early-stage cases. PMID:27462170

  13. Morphological and morphometric aspects of early life stages of piabanha Brycon gouldingi (Characidae).

    PubMed

    Faustino, F; Makino, L C; Neumann, E; Nakaghi, L S O

    2015-05-01

    Adult specimens of piabanha Brycon gouldingi were collected from Rio das Mortes (Mato Grosso, Brazil), adapted to captivity and induced to spawn at Buriti Fisheries (Nova Mutum, MT, Brazil). The early developmental stages of B. gouldingi were then characterized. Samples were collected at pre-determined times from oocyte extrusion to total yolk absorption. Oocyte diameter, total larval length (LT ) and yolk-sac volume were measured. The mean ± s.d. duration of embryo developmental of B. gouldingi was 13·90 ± 0·06 h at 26·40 ± 1·13° C. The mean ± s.d. oocyte diameter was 1·13 ± 0·06 mm with 54% of oocytes ranging from 1·11 to 1·20 mm. Seven stages characterized the early developmental phase of this species: zygote, cleavage, morula, blastula, gastrula, histogenesis-organogenesis and hatching, with unique features related to each stage. At hatching, the larvae measured 3·40 ± 0·07 mm, presented an elongated shape with yolk-sac volume of 0·46 ± 0·08 µl, non-pigmented eyes and exhibited swimming ability. When the yolk was completely absorbed at 55 h post-hatch, mean ± larval LT was 6·68 ± 0·65 mm, the eyes were highly pigmented and the teeth were visible. These are the first reported findings on the initial developmental stages of B. gouldingi and could be used to improve captive breeding management and conservation practices.

  14. 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

  15. 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.

  16. Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

    PubMed

    Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

    2010-05-01

    Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD. PMID

  17. 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.

  18. [Current situation and confusion of sublobar resection for early stage lung cancer].

    PubMed

    Yang, Fan; Wang, Jun

    2015-10-01

    Lobectomy with lymph node dissection has long been the standard surgical procedure for non-small cell lung cancer. However, the increased identification of smaller and smaller and even more indolent tumors by advanced imaging screening rekindled the interest of sublobar resection. Still, existing evidence only supports sublobar resection for radiologically or pathologically "very-early" stage tumors or high-risk patients. Ongoing randomized controlled trials in America, Japan and Europe will address the issue of "radical" application of sublobar resection, as well as an elderly patient trial for "compromized" application initiated by us. These efforts will delineate the utility of sublobar resection in patients with non-small cell lung cancer.

  19. '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. PMID:18298633

  20. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer's disease.

    PubMed

    Krasodomska, Kamila; Lubiński, Wojciech; Potemkowski, Andrzej; Honczarenko, Krystyna

    2010-10-01

    Alzheimer's disease (AD) is one of the most common causes of dementia in the world. Patients with AD frequently complain of vision disturbances that do not manifest as changes in routine ophthalmological examination findings. The main causes of these disturbances are neuropathological changes in the visual cortex, although abnormalities in the retina and optic nerve cannot be excluded. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests are commonly used in ophthalmology to estimate bioelectrical function of the retina and optic nerve. The aim of this study was to determine whether retinal and optic nerve function, measured by PERG and PVEP tests, is changed in individuals in the early stages of AD with normal routine ophthalmological examination results. Standard PERG and PVEP tests were performed in 30 eyes of 30 patients with the early stages of AD. The results were compared to 30 eyes of 30 normal healthy controls. PERG and PVEP tests were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Additionally, neural conduction was measured using retinocortical time (RCT)--the difference between P100-wave latency in PVEP and P50-wave implicit time in PERG. In PERG test, PVEP test, and RCT, statistically significant changes were detected. In PERG examination, increased implicit time of P50-wave (P < 0.03) and amplitudes reductions in P50- and N95-waves (P < 0.0001) were observed. In PVEP examination, increased latency of P100-wave (P < 0.0001) was found. A significant increase in RCT (P < 0.0001) was observed. The most prevalent features were amplitude reduction in N95-wave and increased latency of P100-wave which were seen in 56.7% (17/30) of the AD eyes. In patients with the early stages of AD and normal routine ophthalmological examination results, dysfunction of the retinal ganglion cells as well as of the optic nerve is present, as detected by PERG and PVEP tests. These

  1. Composition effects on the early-stage oxidation kinetics of (001) Cu-Au alloys

    NASA Astrophysics Data System (ADS)

    Zhou, G.-W.; Eastman, J. A.; Birtcher, R. C.; Baldo, P. M.; Pearson, J. E.; Thompson, L. J.; Wang, L.; Yang, J. C.

    2007-02-01

    An in situ environmental transmission electron microscopy study of the nucleation and growth of oxide islands during the early-stage oxidation of (001) Cu1-xAux alloys (x⩽38at.%) was undertaken in order to investigate the effects of alloying on oxide island nucleation behavior and growth kinetics. The kinetic data reveal that Au enhances the nucleation density of oxide islands and suppresses their growth rate. Our results provide insight into reasons for the decreased passivation properties of Cu when alloyed with Au.

  2. Microstructural evolution of 7012 alloy during the early stages of artificial ageing

    SciTech Connect

    Ferragut, R.; Somoza, A.; Tolley, A.

    1999-11-26

    A study of the microstructural evolution of a commercial 7012 (Al-Zn-Mg-Cu) age-hardenable alloy following artificial ageing by high resolution and conventional transmission electron microscopy and positron annihilation lifetime spectroscopy is presented. At the early stages of decomposition, the microstructure included precipitation of either pre-precipitate solute clusters or Guinier-Preston zones and semi-coherent {eta}{prime} precipitates, with typical sizes between 1 and 10 nm. Quantitative information on the size, number density and morphology of the particles present in the microstructure was obtained. The results were correlated with those obtained using positron annihilation lifetime spectroscopy.

  3. '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.

  4. Bone scanning in patients with early breast carcinoma: should it be a routine staging procedure

    SciTech Connect

    Lee, Y.T.

    1981-02-01

    Bone scanning is a sensitive test for the detection of metastatic breast cancer, but not all abnormal findings on bone scan are diagnostic of skeletal metastasis. Recent studies have found a relatively low rate (less than or equal to 5%) of abnormal scans in patients with Stage I and II breast cancers, and only half of those with positive scans subsequently had documented bony metastasis. The overwhelming clinical experiences summarized here question the value of including bone scanning as part of the routine work-up of patients with early breast cancers.

  5. 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.

  6. Origin of the directed movement of protocells in the early stages of the evolution of life.

    PubMed

    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. PMID:22772806

  7. 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. PMID:26610960

  8. 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.

  9. Modeling the early stages of self-assembly in nanophase materials.

    PubMed

    Kozak, John J; Nicolis, C; Nicolis, G

    2007-04-21

    The early stages of self-assembly of the elementary building blocks of nanophase materials are studied. The relative roles of entropic and energetic factors in determining the relative abundance of the final products present is analyzed using both a kinetic mean field model and a mesoscopic approach in which self-assembly is viewed as an encounter-controlled process on a discrete lattice. The relevance of the results in zeolite synthesis in connection with the ordered liquid phases recently discovered in these materials is discussed.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. 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.

  12. Transforming the work of early-stage drug discovery through bioprocess informatics.

    PubMed

    Holzman, Thomas F; Hebert, Eric J

    2005-01-01

    Drug discovery has historically advanced by synergy and chance. These are proving insufficient to meet the needs of the marketplace and the demands of modern medicine. We describe our strategic approaches to building and employing flexible informatics tools to transform and improve the workflows and efficiencies of the early-stages of target development in drug discovery. We contrast our approach to strategies that have recently evolved at startup biotechnology companies who use similar technological approaches to drug development but who are less encumbered by precedent and history.

  13. The effect of tramadol hydrochloride on early life stages of fish.

    PubMed

    Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka

    2016-06-01

    The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride.

  14. 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.

  15. The effect of tramadol hydrochloride on early life stages of fish.

    PubMed

    Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka

    2016-06-01

    The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride. PMID:27208654

  16. 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.

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

    PubMed

    You, Yuqi; Li, Wen

    2016-03-01

    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.

  18. Early outcomes of one-stage combined osteotomy in Legg-Calve´-Perthes disease

    PubMed Central

    Bhuyan, Basant Kumar

    2016-01-01

    Background: Legg-Calve´-Perthes disease (LCPD) is an idiopathic avascular necrosis of the femoral head. There are multiple approaches to the treatment of LCPD ranging from conservative management to a wide variety of surgical methods. Conservative management necessitates extreme degrees of abduction in an orthosis for a longer period of time which further jeopardize capital femoral head vascularity. Surgical containment methods are used in cases where it is desirable. Initial surgical containment methods are varus or varus-derotational osteotomy of the proximal femur or an innominate osteotomy as described by Salter and other pelvic osteotomies. The purpose of this study was to describe the early results of containment methods by one-stage combined osteotomy (femoral varus osteotomy and Salter innominate osteotomy) in patients with severe LCPD. Materials and Methods: 23 children were operated in the age group of 4–9 years for LCPD by one-stage combined osteotomy procedure between January 2005 and June 2012. There were 19 boys and 4 girls, left hip involved in 10 cases and right in 13 cases. Preoperatively, they were classified according to Catterall, Joseph's stage and lateral pillar (LP) classification. Postoperatively, clinical results were evaluated in accordance with Ratliff classification and radiological assessment was made by Mose's index, modified Stulberg classification and Epiphyseal extrusion index. Results: Seventeen hips were Catterall group III, 6 in group IV and all had two or more “head-at-risk” signs. There were 2 patients with stage IIA, 15 were in stage IIB and 6 were in stage IIIA as classified by Joseph's stage of disease. According to LP classification, 11 patients were group B, 3 were group B/C and 9 were in group C. At an average followup of 5.4 years (range 2–9.5 years), the clinical results were good in 12, fair in 9 and poor in 2. According to Mose scale, 8 patients had good results, 13 fair results and 2 had poor results. Based

  19. Accumulation and toxicity of poly aromatic hydrocarbons (PAHs) in early life stages of fish

    SciTech Connect

    Petersen, G.I.; Kristensen, P.

    1995-12-31

    The scientific rationale for QSAR, which relates toxic effect concentrations to octanole-water partition coefficients (log K), is that the internal toxicity thresholds presumably are the same for substances having the same mode of action. This hypothesis, which links bioaccumulation, bioavailability and toxicity, was tested for representatives from a homologous group of PAHs. The bioaccumulation and toxicity of {sup 14}C labelled phenanthrene (log P{sub ow} = 4.57) and pyrene (log P{sub ow} = 5.18) were studied in order to compare the internal lethal and sublethal toxicity thresholds (LD{sub 50}/ED{sub 50}) with the external effect concentrations (LC{sub 50}/EC{sub 50}) in early life stages of zebrafish (Brachydanio rerio). Exposure was initiated with two different life stages, newly fertilized eggs (< 4 hours old) and newly hatched larvae respectively. Both type of experiments were terminated after absorption of the yolk sac. In the bioaccumulation studies the uptake rates were significantly dependent on the life stage with the egg stage having the lowest rate of uptake (due to the reduced permeability of the chorion), while there were no significant difference between the resulting bioaccumulation. In the toxicity experiments the life stage had no effect on the internal toxicity thresholds. Comparison of the internal and external effect concentrations for phenanthrene and pyrene, showed that the external effect concentrations (LC{sub 50} and EC{sub 50}) differed by a factor up to 10 while the internal toxicity thresholds (LD{sub 50} and ED{sub 50}) were not significantly different.

  20. The Problems of Replication in the Early Stages of Evolution: Enumeration of Variants and Spatial Configurations of Replicators

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.

    2014-12-01

    Two main problems of replication in the early stages of evolution are discussed: the problem of exponentially large number of conformational degrees of freedom and the problem of enumeration of variants.

  1. 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

  2. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease

    PubMed Central

    An, Chansik; Choi, Youn Ah; Choi, Dongil; Paik, Yong Han; Ahn, Sang Hoon; Kim, Myeong-Jin; Paik, Seung Woon; Han, Kwang-Hyub

    2015-01-01

    Background/Aims The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate. Methods Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients. Results The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234). Conclusions The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC. PMID:26523271

  3. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma.

    PubMed

    Zhang, Xindong; Gao, Lin; Liu, Zhi-Ping; Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  4. 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.

  5. 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.

  6. Molecular Mechanism of the Early Stage of Amyloidogenic Hexapeptides (NFGAIL) Aggregation

    NASA Astrophysics Data System (ADS)

    Shi, Bi-Yun; Zhou, Bo; Cai, Zhuo-Wei; Xiu, Peng; Yang, Zai-Xing

    2013-10-01

    Peptides/proteins aggregation can give rise to pathological conditions of many human diseases. Small partially ordered oligomers formed in the early stage of aggregation, rather than mature fibrils, are thought to be the main toxicity agent for the living cell. Thus, understanding the pathway and the underlying physical mechanism in the early stage of aggregation is very important for prevention and treatment of these protein functional diseases. Herein we use all-atom molecular dynamics simulations to study the aggregation of four NFGAIL hexapeptides (NFGAIL peptide is a core segment of human islet amyloid polypeptide and exhibits similar aggregation kinetics as the full-length polypeptide). We observe that the peptide monomers in water mainly adopt non-structural coil configurations; the four peptides which are randomly placed in water aggregate spontaneously to partially ordered oligomer (β-sheets) through dimerization or trimerization, with the dimerization predominated. Both parallel and anti-parallel β-sheets are observed. The hydrophobic interactions drive the initial peptides associations, and the subsequent conformational fluctuations promote the formation of more hydrogen bonds between the dangling hydrogen sites in the main chains of peptides.

  7. Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice.

    PubMed

    Good, Jeffrey M; Handel, Mary Ann; Nachman, Michael W

    2008-01-01

    House mice offer a powerful system for dissecting the genetic basis of phenotypes that isolate species in the early stages of speciation. We used a series of reciprocal crosses between wild-derived strains of Mus musculus and M. domesticus to examine F(1) hybrid male sterility, one of the primary phenotypes thought to isolate these species. We report four main results. First, we found significantly smaller testes and fewer sperm in hybrid male progeny of most crosses. Second, in some crosses hybrid male sterility was asymmetric and depended on the species origin of the X chromosome. These observations confirm and extend previous findings, underscoring the central role that the M. musculus X chromosome plays in reproductive isolation. Third, comparisons among reciprocal crosses revealed polymorphism at one or more hybrid incompatibilities within M. musculus. Fourth, the spermatogenic phenotype of this polymorphic interaction appears distinct from previously described hybrid incompatibilities between these species. These data build on previous studies of speciation in house mice and show that the genetic basis of hybrid male sterility is fairly complex, even at this early stage of divergence.

  8. Early-stage development of human induced pluripotent stem cell-derived neurons.

    PubMed

    Ohara, Yuki; Koganezawa, Noriko; Yamazaki, Hiroyuki; Roppongi, Reiko T; Sato, Kaoru; Sekino, Yuko; Shirao, Tomoaki

    2015-12-01

    Recent advances in human induced pluripotent stem cells (hiPSCs) offer new possibilities for biomedical research and clinical applications. Differentiated neurons from hiPSCs are expected to be useful for developing novel methods of treatment for various neurological diseases. However, the detailed process of functional maturation of hiPSC-derived neurons (hiPS neurons) remains poorly understood. This study analyzes development of hiPS neurons, focusing specifically on early developmental stages through 48 hr after cell seeding; development was compared with that of primary cultured neurons derived from the rat hippocampus. At 5 hr after cell seeding, neurite formation occurs in a similar manner in both neuronal populations. However, very few neurons with axonal polarization were observed in the hiPS neurons even after 48 hr, indicating that hiPS neurons differentiate more slowly than rat neurons. We further investigated the elongation speed of axons and found that hiPS neuronal axons were slower. In addition, we characterized the growth cones. The localization patterns of skeletal proteins F-actin, microtubule, and drebrin were similar to those of rat neurons, and actin depolymerization by cytochalasin D induced similar changes in cytoskeletal distribution in the growth cones between hiPS neurons and rat neurons. These results indicate that, during the very early developmental stage, hiPS neurons develop comparably to rat hippocampal neurons with regard to axonal differentiation, but the growth of axons is slower.

  9. 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

    2016-09-01

    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.

  10. Early stage spin-state transition in LaCoO3 investigated by first principles

    NASA Astrophysics Data System (ADS)

    Leighton, C.; Hsu, H.; Cococcioni, M.; Wentzcovitch, R. M.

    2009-12-01

    Thermal-induced spin-state transition in LaCoO3 has been a highly debated phenomenon. The point in controversy is whether the intermediate-spin (IS) state can stably exist, and whether the intermediate-spin or high-spin (HS) state is the first excited state. In our calculation, we have successfully stabilized isolated HS and IS Co in an array of low-spin (LS) Co in LaCoO3 using the local density approximation + Hubbard U (LDA+U) method. The HS/LS (or IS/LS) Co population ratio is set to 1:7, so that the early stage of spin-state transition is properly approximated. The Hubbard U is self-consistently determined by first principles, so that the equation of state and the energy of Co in each spin state can be determined with better accuracy. We show that at low temperature, isolated IS Co has higher energy than isolated HS Co. We also show that low concentration of isolated IS Co can lead to metallic LaCoO3. Therefore, the early stage spin-state transition in LaCoO3 is LS-to-HS transition. This work was supported primarily by the MRSEC Program of the National Science Foundation under Award Number DMR-0212302 and DMR-0819885. It was also partially supported by NSF grants ITR-0426757 (VLab) and EAR 0757903. Calculations were performed at Minnesota Supercomputing Institute (MSI).

  11. 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

    2016-09-01

    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. PMID:27484398

  12. Lithostathine and pancreatitis-associated protein are involved in the very early stages of Alzheimer's disease.

    PubMed

    Duplan, L; Michel, B; Boucraut, J; Barthellémy, S; Desplat-Jego, S; Marin, V; Gambarelli, D; Bernard, D; Berthézène, P; Alescio-Lautier, B; Verdier, J M

    2001-01-01

    According to one of the theories formulated to explain the etiology of Alzheimer's disease (AD), amylosis may reflect a specific inflammatory response. Two inflammatory proteins, lithostathine and PAP, were evidenced by immunohistochemistry in senile plaques and neurofibrillary tangles of patients with AD. In addition, lithostathine and PAP were significantly increased in the cerebrospinal fluid of patients with AD when compared to patients with multiple sclerosis, another inflammatory disease, and to normal control subjects. However, no correlation was observed with age of occurrence. Furthermore, lithostathine and PAP were increased even at the very early stages of AD, and their level remained elevated during the course of the AD unlike TNFalpha whose level, very high at very early stages, regularly decreased. Finally, if part of lithostathine and PAP are synthesized in the brain, a large part comes from serum by passage over the blood-brain barrier. These results indicate (i) the existence of an acute phase response followed by a chronic inflammation in AD, and (ii) that lithostathine and PAP are involved even at the first pre-clinical biochemical events of AD. In addition, because lithostathine undergoes an autolytic cleavage leading to its precipitation and the formation of fibrils, we believe that it may be involved in amyloidosis and tangles by allowing heterogeneous precipitation of other proteins.

  13. 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

  14. 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.

  15. Ultrastructural observations of the early and late stages of gorgonian coral (Junceella juncea) oocytes.

    PubMed

    Tsai, Sujune; Jhuang, Yating; Spikings, Emma; Sung, Ping-Jyun; Lin, Chiahsin

    2014-08-01

    The developmental oogenesis of gorgonian coral was investigated at the histological level. The objective of this study was to examine and improve the understanding of Junceella juncea oogenesis using ultrastructural methods, such as histological sectioning and transmission electron microscopy. At least three types of yolk materials were observed in this study: yolk body, lipid granules and cortical alveoli. Some of the complex yolk materials were encompassed by concentric or arched layers of smooth and rough endoplasmic reticulum and the Golgi complex in early stage oocytes. Different types of vesicles were found in both early and late stage oocytes and some granules could be seen inside the empty vesicles. This may be a possible method for elaborating complex yolk materials. Homogeneous yolks from different types of inclusions were abundant and the autosynthesis of yolk may be a major mechanism in J. juncea oocytes. This is the first report of the ultrastructural observation of oogenesis in gorgonian coral species using transmission electron microscopy. Our study obtained relatively detailed information at the ultrastructural level, and it provides an overview of the oocyte ultrastucture of the gorgonian coral J. juncea.

  16. Social Network Effects of Nonlifesaving Early-Stage Breast Cancer Detection on Mammography Rates

    PubMed Central

    Parker, Andrew M.

    2014-01-01

    Objectives. We estimated the effect of anecdotes of early-stage, screen-detected cancer for which screening was not lifesaving on the demand for mammography. Methods. We constructed an agent-based model of mammography decisions, in which 10 000 agents that represent women aged 40 to 100 years were linked together on a social network, which was parameterized with a survey of 716 women conducted through the RAND American Life Panel. Our model represents a population in equilibrium, with demographics reflecting the current US population based on the most recent available census data. Results. The aggregate effect of women learning about 1 category of cancers—those that would be detected but would not be lethal in the absence of screening—was a 13.8 percentage point increase in annual screening rates. Conclusions. Anecdotes of detection of early-stage cancers relayed through social networks may substantially increase demand for a screening test even when the detection through screening was nonlifesaving. PMID:25322304

  17. Time-resolved EUV spectroscopy in the early stage of laser ablation of carbon

    NASA Astrophysics Data System (ADS)

    Loiseleur, Pierre; Hansen, Tue N.; Larour, Jean; Lunney, James G.

    2002-09-01

    In the early stages of laser ablation the combination of high density and optical opacity makes it difficult to use visible spectroscopy for plasma diagnosis. However, these problems can be overcome by working at shorter wavelengths in the EUV. We have used time-resolved EUV emission spectroscopy to study the early stages (1-30 ns) of plasma development in the laser ablation of carbon at an irradiance of 5 GW cm -2. The ablation was done using a 6 ns Nd:YAG laser at 1.06 μm. The spectra were recorded using a grazing incidence spectrometer with a 5 ns-gated micro-channel plate (MCP) detector. An ion probe operating in the time-of-flight mode was used to measure the ion velocity distribution of the plasma outflow. In the 10-35 nm region the predominant line emission was due to Li-like carbon. The temporal variation of the electron density and temperature was deduced by fitting the observed spectrum to a synthetic spectrum calculated using the FLY numerical model of the plasma ionisation and excitation. The temperature deduced from spectroscopy was in good agreement with the estimation from the measured ion velocity distribution in the plasma outflow.

  18. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma

    PubMed Central

    Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  19. 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.

  20. Dislocation Multiplication in the Early Stage of Deformation in Mo Single Crystals

    SciTech Connect

    Hsiung, L.; Lassila, D.H.

    2000-03-02

    Initial dislocation structure in annealed high-purity Mo single crystals and deformation substructure in a crystal subjected to 1% compression have been examined and studied using transmission electron microscopy (TEM) techniques in order to investigate dislocation multiplication mechanisms in the early stage of plastic deformation. The initial dislocation density is in a range of 10{sup 6} {approx} 10{sup 7} cm{sup -2}, and the dislocation structure is found to contain many grown-in superjogs along dislocation lines. The dislocation density increases to a range of 10{sup 8} {approx} 10{sup 9} cm{sup -2}, and the average jog height is also found to increase after compressing for a total strain of 1%. It is proposed that the preexisting jogged screw dislocations can act as (multiple) dislocation multiplication sources when deformed under quasi-static conditions. The jog height can increase by stress-induced jog coalescence, which takes place via the lateral migration (drift) of superjogs driven by unbalanced line-tension partials acting on link segments of unequal lengths. The coalescence of superjogs results in an increase of both link length and jog height. Applied shear stress begins to push each link segment to precede dislocation multiplication when link length and jog height are greater than critical lengths. This ''dynamic'' dislocation multiplication source is suggested to be crucial for the dislocation multiplication in the early stage of plastic deformation in Mo.

  1. 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.

  2. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma

    PubMed Central

    Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data.

  3. The Chromosomes of Turkey Embryos during Early Stages of Parthenogenetic Development

    PubMed Central

    Harada, Ko; Buss, Edward G.

    1981-01-01

    In the early stages of parthenogenetic development in turkey eggs, many blastoderms are mosaics of haploid, diploid and polyploid cells. The genome composition of these blastoderms can be identified by C-banding. They may be generally described as either A-Z/2A-ZZ/nA-nZ or A-W/2A-WW/nA-nW and are found in a nearly 1:1 ratio. The blastoderms showing the W body (W+) become lethal within two days of incubation. The haploid cell proportion decreases rapidly during the early stage of development, and, as haploid cells decrease, the proportion of polyploid cells appears to increase. At six days of incubation, various kinds of parthenogenetic development can be observed. Their genome compositions are either diploid (2A-ZZ) or mosaic (A-Z/2A-ZZ). These findings suggest that diploid parthenogenesis occurs by either suppression of meiosis II or chromosome doubling some time after the first cleavage division. The frequent occurrence of mosaic blastoderms indicates that the majority, if not all, of the parthenogenetic embryos initiate their development in haploid ova. PMID:7327389

  4. Cost calculations at early stages of nuclear research facilities in the nordic countries

    SciTech Connect

    Iversen, Klaus; Salmenhaara, Seppo; Backe, Steinar; Cato, Anna; Lindskog, Staffan; Callander, Clas; Efraimsson, Henrik; Andersson, Inga; Sjoeblom, Rolf

    2007-07-01

    The Nordic countries Denmark, Norway and Sweden, and to some extent also Finland, had very large nuclear research and development programs for a few decades starting in the nineteen fifties. Today, only some of the facilities are in use. Some have been decommissioned and dismantled while others are at various stages of planning for shutdown. The perspective ranges from imminent to several decades. It eventually became realized that considerable planning for the future decommissioning is warranted and that an integral part of this planning is financial, including how financial funds should be acquired, used and allocated over time. This necessitates that accurate and reliable cost estimates be obtained at all stages. However, this is associated with fundamental difficulties and treacherous complexities, especially for the early ones. Eventually, Denmark and Norway decided not to build any nuclear power plants while Finland and Sweden did. This is reflected in the financing where the latter countries have established systems with special funds in which money is being collected now to cover the future costs for the decommissioning of the research facilities. Nonetheless, the needs for planning for the decommissioning of nuclear research facilities are very similar. However, they differ considerably from those of nuclear power reactors, especially with regard to cost calculations. It has become apparent in the course of work that summation types of cost estimation methodologies give rise to large systematic errors if applied at early stages, in which case comparison based assessments are less biased and may be more reliable. Therefore, in order to achieve the required quality of the cost calculations, it is necessary that data and experience from authentic cases be utilized in models for cost calculations. It also implies that this calculation process should include a well adopted learning process. Thus, a Nordic co-operation has been established for the exchange and

  5. 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.

  6. 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

  7. Trefoil Factor 1 Excretion Is Increased in Early Stages of Chronic Kidney Disease.

    PubMed

    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.

  8. Arm Swing Magnitude and Asymmetry During Gait in the Early Stages of Parkinson's Disease

    PubMed Central

    Lewek, Michael D.; Poole, Roxanne; Johnson, Julia; Halawa, Omar; Huang, Xuemei

    2009-01-01

    The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in “off” state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p=0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p=0.907) or less (p=0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9±7.9%) compared to the control group (asymmetry angle: 5.1±4.0%; p=0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD. PMID:19945285

  9. Effect of chronic copper and pentachlorophenol exposure to early life stages of Xenopus laevis

    SciTech Connect

    Fort, D.J.; Stover, E.L.

    1995-12-31

    An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorophenol, from 0 d to 4 d (standard Frog Embryo Teratagenesis Assay Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased in each successive time period. Continuous exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5/{micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.

  10. Differential gene expression profile in bovine blastocysts resulting from hyperglycemia exposure during early cleavage stages.

    PubMed

    Cagnone, Gaël L M; Dufort, Isabelle; Vigneault, Christian; Sirard, Marc-André

    2012-02-01

    To understand the compromised survival of embryos derived from assisted reproductive techniques, transcriptome survey of early embryonic development has shown the impact of in vitro culture environment on gene expression in bovine or other living species. However, how the differentially expressed genes translate into developmentally compromised embryos is unresolved. We therefore aimed to characterize transcriptomic markers expressed by bovine blastocysts cultured in conditions that are known to impair embryo development. As increasing glucose concentrations has been shown to be stressful for early cleavage stages of mammalian embryos and to decrease subsequent blastocyst survival, in vitro-matured/fertilized bovine zygotes were cultured in control (0.2 mM) or high-glucose (5 mM) conditions until the 8- to 16-cell stage, and then transferred to control media until they reached the blastocyst stage. The concentration of 5 mM glucose was chosen as a stress treatment because there was a significant effect on blastocyst rate without the treatment's being lethal as with 10 mM. Microarray analysis revealed gene expression differences unrelated to embryo sex or hatching. Overrepresented processes among differentially expressed genes in treated blastocysts were extracellular matrix signalling, calcium signaling, and energy metabolism. On a pathophysiological level, higher glucose treatment impacts pathways associated with diabetes and tumorigenesis through genes controlling the Warburg effect, i.e., emphasis on use of anaerobic glycolysis rather than oxidative phosphorylation. These results allowed us to conclude that disruption of in vitro preattachment development is concomitant with gene expression modifications involved in metabolic control.

  11. 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. PMID:24100467

  12. High prevalence of abnormal adrenal response in girls with central precocious puberty at early pubertal stages.

    PubMed

    Lazar, L; Kauli, R; Bruchis, C; Nordenberg, J; Galatzer, A; Pertzelan, A

    1995-10-01

    Abnormal adrenal response is often observed in girls with precocious adrenarche (1). We studied the adrenal response in 112 girls with idiopathic true central precocious puberty (CPP) at early stages of puberty compared to that in 21 girls with normal puberty (controls). The aims of this study were to determine the prevalence of abnormal adrenal response at early stages of puberty, the possible correlation of abnormal adrenal response with pubertal signs at onset of puberty and with plasma androgen levels, and a possible association with the activity of the hypothalamic-pituitary-gonadal (HPG) axis. All participants underwent a combined i.v. adrenocorticotropic hormone (ACTH)-gonadotropin-releasing hormone (GnRH) test at Tanner stage 2-3: 62 of the CPP girls before and 50 during treatment with GnRH analog. The stimulated levels of 17-hydroxypregnenolone (17OHPreg) and the stimulated 17OHPreg/17-hydroxyprogesterone ratio were analyzed and compared to previously reported norms. The result revealed three patterns of adrenal response: normal (17OHPreg < or = 24 nmol/l and 17OHPreg/17OHP ratio < or = 7) in 50/112 (44.6%) CPP patients and 17/21 (80.9%) controls; exaggerated (17OHPreg > 24 nmol/l, 17OHPreg/17OHP ratio < or = 7) in 50/112 (44.6%) CPP patients and 3/21 (14.3%) controls; and non-classical 3 beta-hydroxysteroid dehydrogenase deficiency (17OHPreg > 24 nmol/l and 17OHPreg/17OHP ratio > 7) in 12/112 (10.8%) CPP patients and 1/21 (4.8%) controls. The clinical features at onset of puberty were comparable in all girls with the CPP in spite of the different adrenal response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. 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. PMID:15039986

  14. 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.

  15. Investigating the early stages of mineral precipitation by potentiometric titration and analytical ultracentrifugation.

    PubMed

    Kellermeier, Matthias; Cölfen, Helmut; Gebauer, Denis

    2013-01-01

    Despite the importance of crystallization for various areas of research, our understanding of the early stages of the mineral precipitation from solution and of the actual mechanism of nucleation is still rather limited. Indeed, detailed insights into the processes underlying nucleation may enable a systematic development of novel strategies for controlling mineralization, which is highly relevant for fields ranging from materials chemistry to medicine. In this work, we describe experimental aspects of a quantitative assay, which relies on pH titrations combined with in situ metal ion potentiometry and conductivity measurements. The assay has originally been designed to study the crystallization of calcium carbonate, one of the most abundant biominerals. However, the developed procedures can also be readily applied to any compound containing cations for which ion-selective electrodes are available. Besides the possibility to quantitatively assess ion association prior to nucleation and to directly determine thermodynamic solubility products of precipitated phases, the main advantage of the crystallization assay is the unambiguous identification of the different stages of precipitation (i.e., prenucleation, nucleation, and early postnucleation) and the characterization of the multiple effects of additives. Furthermore, the experiments permit targeted access to distinct precursor species and intermediate stages, which thus can be analyzed by additional methods such as cryo-electron microscopy or analytical ultracentrifugation (AUC). Regarding ion association in solution, AUC detects entities significantly larger than simple ion pairs, so-called prenucleation clusters. Sedimentation coefficient values and distributions obtained for the calcium carbonate system are discussed in light of recent insights into the structural nature of prenucleation clusters.

  16. Directional information flows between brain hemispheres during presleep wake and early sleep stages.

    PubMed

    Bertini, Mario; Ferrara, Michele; De Gennaro, Luigi; Curcio, Giuseppe; Moroni, Fabio; Vecchio, Fabrizio; De Gasperis, Marco; Rossini, Paolo Maria; Babiloni, Claudio

    2007-08-01

    Neuroscientists' efforts to better understand the underlying processes of human consciousness are growing in a variety of multidisciplinary approaches. Relevant within these are the studies aimed at exploring the physiological substratum of the propagation and reduction of cerebral-namely, corticocortical-communication flows. However, the preferential direction of the information flow between brain hemispheres is as yet largely unknown. It is the aim of the present research to study the communication flows between brain hemispheres, their directionality, and their regional variations across wake-sleep states. A second aim is to investigate the possibility of an association between different brain rhythms and different preferred directions of the information flow. Scalp electroencephalograms (EEGs) were recorded in 10 normal volunteers from wakefulness to early sleep stages (viz., resting wakefulness, sleep stages 2 and 4, and rapid eye movement [REM] of the first sleep cycle). EEG rhythms of interest were delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz), and beta (16-30 Hz). The direction of the interhemispheric information flow was evaluated by computing directed transformation function from these EEG rhythms. Interhemispheric directional flows varied as a function of the state of consciousness (wake and early sleep stages) and in relation to different cerebral areas. Across wake to sleep states, we found that delta and beta rhythms convey interhemispheric signals with opposite directions: preferred right to left hemisphere direction for delta and left to right for beta rhythms. A log correlation confirmed that the trend of low to high EEG frequencies-traditionally associated with an increasing state of vigilance-was significantly related to the direction of the communication flow from the left to right hemisphere. This evidence might open the way for a variety of research lines on different psychophysiological and pathological conditions. PMID

  17. Lack of miRNA Misregulation at Early Pathological Stages in Drosophila Neurodegenerative Disease Models

    PubMed Central

    Reinhardt, Anita; Feuillette, Sébastien; Cassar, Marlène; Callens, Céline; Thomassin, Hélène; Birman, Serge; Lecourtois, Magalie; Antoniewski, Christophe; Tricoire, Hervé

    2012-01-01

    Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80–84 year-old Europeans) or Parkinson disease (PD, 1.4% prevalence for >55 years old) share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence) and frontotemporal lobar degeneration (FTLD, 0.02% prevalence), a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs (miRNAs), a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias, and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for seven diseases (PD, 3 FTLD, 3 dominant ataxias) that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non-coding CAG repeat RNAs (sCAG) in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases. PMID:23115562

  18. 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.

  19. 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.

  20. Computer simulation on the cooperation of functional molecules during the early stages of evolution.

    PubMed

    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 emergence of single

  1. 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

  2. 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.

  3. 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.

  4. 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. PMID:19120146

  5. 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. PMID:27435496

  6. [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.

  7. 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.

  8. 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...

  9. 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

  10. Altered Gray Matter Structural Covariance Networks in Early Stages of Alzheimer's Disease.

    PubMed

    Montembeault, Maxime; Rouleau, Isabelle; Provost, Jean-Sébastien; Brambati, Simona Maria

    2016-06-01

    Clinical symptoms observed in Alzheimer's disease (AD) patients may reflect variations within specific large-scale brain networks, modeling AD as a disconnection syndrome. The present magnetic resonance imaging study aims to compare the organization of gray matter structural covariance networks between 109 cognitively unimpaired controls (CTRL) and 109 AD patients positive to beta-amyloid at the early stages of the disease, using voxel-based morphometry. The default-mode network (DMN; medial temporal lobe subsystem) was less extended in AD patients in comparison with CTRL, with a significant decrease in the structural association between the entorhinal cortex and the medial prefrontal and the dorsolateral prefrontal cortices. The DMN (midline core subsystem) was also less extended in AD patients. Trends toward increased structural association were observed in the salience and executive control networks. The observed changes suggest that early disruptions in structural association between heteromodal association cortices and the entorhinal cortex could contribute to an isolation of the hippocampal formation, potentially giving rise to the clinical hallmark of AD, progressive memory impairment. It also provides critical support to the hypothesis that the reduced connectivity within the DMN in early AD is accompanied by an enhancement of connectivity in the salience and executive control networks.

  11. 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.

  12. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  13. 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

  14. 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

  15. Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism

    PubMed Central

    Peng, Huan; Cui, Jiangkuan; Long, Haibo; Huang, Wenkun; Kong, Lingan; Liu, Shiming; He, Wenting; Hu, Xianqi; Peng, Deliang

    2016-01-01

    Pectate lyases are known to play a key role in pectin degradation by catalyzing the random cleavage of internal polymer linkages (endo-pectinases). In this paper, four novel cDNAs, designated Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7, that encode pectate lyases were cloned and characterized from the soybean cyst nematode, Heterodera glycines. The predicted protein sequences of HG-PEL-3, HG-PEL-4 and HG-PEL-6 differed significantly in both their amino acid sequences and their genomic structures from other pectate lyases of H. glycines (HG-PEL-1, HG-PEL-2 and HG-PEL-7). A phylogenetic study revealed that the pectate lyase proteins of H. glycines are clustered into distinct clades and have distinct numbers and positioning of introns, which suggests that the pectate lyase genes of H. glycines may have evolved from at least two ancestral genes. A Southern blot analysis revealed that multiple Hg-pel-6-like genes were present in the H. glycines genome. In situ hybridization showed that four novel pectate lyases (Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7) were actively transcribed in the subventral esophageal gland cells. A semi-quantitative RT-PCR assay supported the finding that the expression of these genes was strong in the egg, pre-parasitic second-stage juvenile (J2) and early parasitic J2 stages and that it declined in further developmental stages of the nematode. This expression pattern suggests that these proteins play a role in the migratory phase of the nematode life cycle. Knocking down Hg-pel-6 using in vitro RNA interference resulted in a 46.9% reduction of the number of nematodes that invaded the plants and a 61.5% suppression of the development of H. glycines females within roots compared to the GFP-dsRNA control. Plant host-derived RNAi induced the silencing of the Hg-pel-6gene, which significantly reduced the nematode infection levels at 7 Days post inoculation (dpi). Similarly, this procedure reduced the number of female adults at 40 dpi, which suggests

  16. Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism.

    PubMed

    Peng, Huan; Cui, Jiangkuan; Long, Haibo; Huang, Wenkun; Kong, Lingan; Liu, Shiming; He, Wenting; Hu, Xianqi; Peng, Deliang

    2016-01-01

    Pectate lyases are known to play a key role in pectin degradation by catalyzing the random cleavage of internal polymer linkages (endo-pectinases). In this paper, four novel cDNAs, designated Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7, that encode pectate lyases were cloned and characterized from the soybean cyst nematode, Heterodera glycines. The predicted protein sequences of HG-PEL-3, HG-PEL-4 and HG-PEL-6 differed significantly in both their amino acid sequences and their genomic structures from other pectate lyases of H. glycines (HG-PEL-1, HG-PEL-2 and HG-PEL-7). A phylogenetic study revealed that the pectate lyase proteins of H. glycines are clustered into distinct clades and have distinct numbers and positioning of introns, which suggests that the pectate lyase genes of H. glycines may have evolved from at least two ancestral genes. A Southern blot analysis revealed that multiple Hg-pel-6-like genes were present in the H. glycines genome. In situ hybridization showed that four novel pectate lyases (Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7) were actively transcribed in the subventral esophageal gland cells. A semi-quantitative RT-PCR assay supported the finding that the expression of these genes was strong in the egg, pre-parasitic second-stage juvenile (J2) and early parasitic J2 stages and that it declined in further developmental stages of the nematode. This expression pattern suggests that these proteins play a role in the migratory phase of the nematode life cycle. Knocking down Hg-pel-6 using in vitro RNA interference resulted in a 46.9% reduction of the number of nematodes that invaded the plants and a 61.5% suppression of the development of H. glycines females within roots compared to the GFP-dsRNA control. Plant host-derived RNAi induced the silencing of the Hg-pel-6gene, which significantly reduced the nematode infection levels at 7 Days post inoculation (dpi). Similarly, this procedure reduced the number of female adults at 40 dpi, which suggests

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

    NASA Astrophysics Data System (ADS)

    Franke, A.; Clemmesen, C.

    2011-07-01

    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 the early developmental stages, the most sensitive stages in the 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 consequently should 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 and could affect the ecosystem and fisheries. 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

  18. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2.

    PubMed

    Doege, Claudia A; Inoue, Keiichi; Yamashita, Toru; Rhee, David B; Travis, Skylar; Fujita, Ryousuke; Guarnieri, Paolo; Bhagat, Govind; Vanti, William B; Shih, Alan; Levine, Ross L; Nik, Sara; Chen, Emily I; Abeliovich, Asa

    2012-08-30

    Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by using the pluripotency factors Oct4, Sox2, Klf4 and c-Myc (together referred to as OSKM). iPSC reprogramming erases somatic epigenetic signatures—as typified by DNA methylation or histone modification at silent pluripotency loci—and establishes alternative epigenetic marks of embryonic stem cells (ESCs). Here we describe an early and essential stage of somatic cell reprogramming, preceding the induction of transcription at endogenous pluripotency loci such as Nanog and Esrrb. By day 4 after transduction with OSKM, two epigenetic modification factors necessary for iPSC generation, namely poly(ADP-ribose) polymerase-1 (Parp1) and ten-eleven translocation-2 (Tet2), are recruited to the Nanog and Esrrb loci. These epigenetic modification factors seem to have complementary roles in the establishment of early epigenetic marks during somatic cell reprogramming: Parp1 functions in the regulation of 5-methylcytosine (5mC) modification, whereas Tet2 is essential for the early generation of 5-hydroxymethylcytosine (5hmC) by the oxidation of 5mC (refs 3,4). Although 5hmC has been proposed to serve primarily as an intermediate in 5mC demethylation to cytosine in certain contexts, our data, and also studies of Tet2-mutant human tumour cells, argue in favour of a role for 5hmC as an epigenetic mark distinct from 5mC. Consistent with this, Parp1 and Tet2 are each needed for the early establishment of histone modifications that typify an activated chromatin state at pluripotency loci, whereas Parp1 induction further promotes accessibility to the Oct4 reprogramming factor. These findings suggest that Parp1 and Tet2 contribute to an epigenetic program that directs subsequent transcriptional induction at pluripotency loci during somatic cell reprogramming. PMID:22902501

  19. What do we know about the initiation and early stages of brittle faulting in crystalline rocks?

    NASA Astrophysics Data System (ADS)

    Crider, J. G.

    2011-12-01

    The styles of initiation and subsequent growth of faults control fault length-slip scaling, the internal structure of fault zones, and fault-rock properties, influencing seismogenic behavior and fluid flow along the faults. Observations by many researchers over the last several decades have illustrated that faults in the upper crust initiate on pre-existing (inherited) or precursory (early-formed) structures and grow by the mechanical interaction and linkage of these structures. These pre-existing and precursory structures are typically mode I fractures (joints, veins, dikes) but may also be semi-brittle shear zones (such as deformation bands in porous sandstone). Research in the granitic outcrops of the central Sierra Nevada (California) has provided significant insight into the geometry and fundamental mechanics of the early stages of fault development. This work has shown that faults in plutonic rocks initiate on pre-existing or precursory joints or dikes and that the discontinuous nature of early mode I fractures has a strong influence on the subsequent development of the fault zone. In basalt, we have similarly observed the important influence of preexisting joints, and, at a broader scale, precursory, semi-brittle shear zones in the form of fault-tip monoclines. In metamorphic rocks, foliation appears to control the initial development of faults, influencing fault orientation, or enabling precursory structures such as kink bands. Kink bands, like deformation bands in porous sandstone, accommodate only small strains before locking, but then become strong inclusions in the material, serving to localize brittle fractures. The quasi-static mechanics of isotropic, isothermal linear-elastic materials in two and three dimensions provides first order understanding of controls on interaction and linkage of early structures, including the concentration of stresses and local stress reorientation. Fruitful research directions important to faulting in crystalline rock

  20. Ultrastructure of the early embryonic stages of Corallobothrium fimbriatum (Cestoda: Proteocephalidea).

    PubMed

    Młocicki, Daniel; Swiderski, Zdzisław; Conn, David Bruce

    2010-10-01

    Cellular details of early embryogenesis have been studied extensively among cyclophyllidean cestodes, but have been reported for only 2 species of the order Proteocephalidea, both belonging to the genus Proteocephalus. Thus, we performed a detailed ultrastructural analysis of early embryos of a second species, Corallobothrium fimbriatum, including early events in the formation of the embryonic envelopes. Adult worms were collected from the small intestine of brown bullhead catfish, Ameiurus nebulosus, from the St. Lawrence River in North America and processed by standard methods for transmission electron microscopy. The vitelline capsule consists of 2 closely apposed electron-dense membranous layers, separated by a more electron-lucent material. The 2 vitellocytes that accompany each oocyte contain numerous ribosomes, vesicles, and lipid droplets. These fuse to form a vitelline syncytium, which elongates and almost completely encircles the cleaving embryo by the 4-blastomere stage, forming a partial lipid-rich cellular envelope that undergoes apoptosis as cleavage continues. This envelope is later replaced by outer and inner embryonic envelopes. The outer envelope derives from the fusion of the vitelline syncytium with the cytoplasm of macromeres, whereas the inner envelope originates from 3 mesomeres. Simultaneous to the formation of the embryonic envelopes, other blastomeres multiply and differentiate, while some micromeres undergo degeneration or apoptosis. In most respects, ultrastructural features of early C. fimbriatum embryos closely resemble those of previously studied Proteocephalus longicollis, but differ somewhat from those of other orders. This demonstrates that, despite marked ultrastructural heterogeneity within some orders such as the Cyclophyllidea, some embryonic traits distinguish cestode orders from each other.

  1. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients.

    PubMed

    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

    2016-03-01

    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 = 0.811, and e

  2. 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

  3. Early stages of pediatric bipolar disorder: retrospective analysis of a Czech inpatient sample

    PubMed Central

    Goetz, Michal; Novak, Tomas; Vesela, Marie; Hlavka, Zdenek; Brunovsky, Martin; Povazan, Michal; Ptacek, Radek; Sebela, Antonin

    2015-01-01

    Background Approximately 30%–60% of adults diagnosed with bipolar disorder (BD) report onset between the ages 15 and 19 years; however, a correct diagnosis is often delayed by several years. Therefore, investigations of the early features of BD are important for adequately understanding the prodromal stages of the illness. Methods A complete review of the medical records of 46 children and adolescents who were hospitalized for BD at two psychiatric teaching centers in Prague, Czech Republic was performed. Frequency of BD in all inpatients, age of symptom onset, phenomenology of mood episodes, lifetime psychiatric comorbidity, differences between very-early-onset (<13 years of age) and early-onset patients (13–18 years), and differences between the offspring of parents with and without BD were analyzed. Results The sample represents 0.83% of the total number of inpatients (n=5,483) admitted during the study period at both centers. BD often started with depression (56%), followed by hypomania (24%) and mixed episodes (20%). The average age during the first mood episode was 14.9 years (14.6 years for depression and 15.6 years for hypomania). Seven children (15%) experienced their first mood episode before age 13 years (very early onset). Traumatic events, first-degree relatives with mood disorders, and attention deficit hyperactivity disorder were significantly more frequent in the very-early-onset group vs the early-onset group (13–18 years) (P≤0.05). The offspring of bipolar parents were significantly younger at the onset of the first mood episode (13.2 vs 15.4 years; P=0.02) and when experiencing the first mania compared to the offspring of non-BD parents (14.3 vs 15.9 years; P=0.03). Anxiety disorders, substance abuse, specific learning disabilities, and attention deficit hyperactivity disorder were the most frequent lifetime comorbid conditions. Conclusion Clinicians must be aware of the potential for childhood BD onset in patients who suffer from

  4. Less radical surgery for early-stage cervical cancer: To what extent do we justify it?-Our belief.

    PubMed

    Thomakos, Nikolaos; Trachana, Sofia-Paraskevi; Davidovic-Grigoraki, Miona; Rodolakis, Alexandros

    2016-08-01

    Cancer of the uterine cervix, following breast cancer, is the second leading cause of death among gynecological cancers in the developed world. Traditionally, surgical management of early-stage cervical carcinoma is considered as a "sterilizing" procedure, since the uterus is removed. Nowadays, because of the postponement of childbearing to an older age, women younger than 45 years old who are diagnosed with early-stage cervical cancer have a strong desire to preserve fertility. Radical trachelectomy (vaginal or abdominal route) is used for fertility preservation in cases of early-stage (International Federation of Gynecology and Obstetrics Stages IA-IB1) cervical carcinomas with remarkable oncological and obstetrical outcomes. However, less radical approaches for ideal candidates may prove safe when fertility preservation is probably feasible. PMID:27590369

  5. 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

  6. Activity of Monoamine Oxidase in the Nigrostriatal System at Presymptomatic and Early Symptomatic Stages of Parkinsonism in Mice.

    PubMed

    Khakimova, G R; Kozina, E A; Buneeva, O A; Aksenova, L N; Medvedev, A E; Ugryumov, M V

    2015-08-01

    Activities of monoamine oxidases A and B were examined on the models of presymptomatic and early symptomatic stages of Parkinson's disease developed in mice treated with MPTP, a specific neurotoxin affecting dopaminergic neurons. Activity of monoamine oxidases A, the key enzyme of dopamine degradation, is increased in neuronal somas during the symptomatic stage, and it is augmented in the axons during both stages. Neuronal activity of monoamine oxidases A is higher during the symptomatic stage than that during the presymptomatic stage, which can explain depletion of intercellular dopamine and appearance of motor disturbances. Activity of monoamine oxidase B in the striatum is reduced during the presymptomatic stage, but returns to the control level during the symptomatic stage. Variation in monoamine oxidase activity seems to reflect the compensatory mechanisms triggered in degrading nigrostriatal dopaminergic system.

  7. Investigating genetic discrimination in Australia: opportunities and challenges in the early stages.

    PubMed

    Taylor, Sandra D; Otlowski, Margaret F; Barlow-Stewart, Kristine K; Treloar, Susan A; Stranger, Mark; Chenoweth, Kellie

    2004-08-01

    Genetic discrimination, defined as the differential treatment of individuals or their relatives on the basis of actual or presumed genetic differences, is an emerging issue of interest in academic, clinical, social and legal contexts. While its potential significance has been discussed widely, verified empirical data are scarce. Genetic discrimination is a complex phenomenon to describe and investigate, as evidenced by the recent Australian Law Reform Commission inquiry in Australia. The authors research project, which commenced in 2002, aims to document the multiple perspectives and experiences regarding genetic discrimination in Australia and inform future policy development and law reform. Data are being collected from consumers, employers, insurers and the legal system. Attempted verification of alleged accounts of genetic discrimination will be a novel feature of the research. This paper overviews the early stages of the research, including conceptual challenges and their methodological implications. PMID:15460616

  8. Photoacoustic Molecular Imaging: From Multiscale Biomedical Applications Towards Early-Stage Theranostics.

    PubMed

    Liu, Yajing; Nie, Liming; Chen, Xiaoyuan

    2016-05-01

    Photoacoustic imaging (PAI) has ushered in a new era of observational biotechnology and has facilitated the exploration of fundamental biological mechanisms and clinical translational applications, which has attracted tremendous attention in recent years. By converting laser into ultrasound emission, PAI combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. This evolutional technique enables multiscale and multicontrast visualization from cells to organs, anatomy to function, and molecules to metabolism with high sensitivity and specificity. The state-of-the-art developments and applications of PAI are described in this review. Future prospects for clinical use are also highlighted. Collectively, PAI holds great promise to drive biomedical applications towards early-stage theranostics. PMID:26924233

  9. Direct Monte Carlo Simulations of the Intermediate Experimental Vehicle at Early Stages of Reentry

    NASA Astrophysics Data System (ADS)

    Banyai, T.; Torres, E.; Kashkovsky, A. V.; Vashchenkov, P. V.; Ivanov, M. S.; Rambaud, P.

    2011-05-01

    Within the European Space Agency (ESA) framework program FLPP Next Generation Launcher (NGL) preparatory activities on System, In-Flight Experimentation and Aerothermodynamics Period 1, Step 2, von Karman Institute (VKI) has to perform ground testing and numerical simulations to contribute to the aerothermodynamic database of the Intermediate eXperimental Vehicle (IXV) along its trajectory during re-entry. The present article summarizes the part of these activities in relation with the evaluation of the aerodynamic properties in the early stages of reentry. Due to the rarefied nature of the higher atmosphere, the computations were carried out by means of Direct Simulation of Monte Carlo (DSMC) method. The aim of this work was to a., validate the methodology used at VKI, b., perform computations at several points along the trajectory and c., assess the feasibility of joint simulation of rarefied flow and thrusters.

  10. Early life stage (ELS) toxicity of sucralose to fathead minnows, Pimephales promelas.

    PubMed

    Stoddard, K I; Huggett, D B

    2014-10-01

    Sucralose, an intense artificial sweetener, has been detected in wastewater and surface waters at concentrations ranging from ng/L to low µg/L. Although over a hundred studies have been conducted to evaluate the safety of sucralose for human consumption, few studies have focused on the chronic ecotoxicological effects of this compound in fish. As a remedy to this data gap, an early-life stage toxicity test was conducted to assess the effects of sucralose on hatching, survival, and growth of fathead minnows (Pimephales promelas). Hatching, survival, and growth were unaffected by 98 mg/L of sucralose. The Lowest-Observed-Effect Concentration (LOEC) and the No-Observed-Effect Concentration (NOEC) for fathead minnows determined by this study are >98 and 98 mg/L, respectively. The results from this study suggest that the concentrations of sucralose detected in the environment are well below those required to cause adverse effects to developing aquatic organisms. PMID:25120258

  11. 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.

  12. Highly anisotropic and strongly dissipative hydrodynamics for early stages of relativistic heavy-ion collisions

    SciTech Connect

    Florkowski, Wojciech; Ryblewski, Radoslaw

    2011-03-15

    We introduce a new framework of highly anisotropic hydrodynamics that includes dissipation effects. Dissipation is defined by the form of the entropy source that depends on the pressure anisotropy and vanishes for the isotropic fluid. With a simple ansatz for the entropy source obeying general physical requirements, we are led to a nonlinear equation describing the time evolution of the anisotropy in purely longitudinal boost-invariant systems. Matter that is initially highly anisotropic approaches naturally the regime of the perfect fluid. Thus, the resulting evolution agrees with the expectations about the behavior of matter produced at the early stages of relativistic heavy-ion collisions. The equilibration is identified with the processes of entropy production.

  13. Early stages of superplasticity and positron lifetime spectroscopy in an Al-Mg-Cu alloy

    SciTech Connect

    Ayciriex, M.D.; Romero, R.; Somoza, A.

    1996-07-01

    In the present paper, by using positron lifetime technique, a careful study is carried out to analyze the microstructural changes induced on samples of an Al-based commercial alloy (Al-Mg-Cu-Mn-Cr) by superplastic deformation in the early stages of superplastic behavior of the alloy (strain range from 0.2% to 100%). These results are compared with those obtained on specimens only heat treated at the same temperature and for a time equivalent to the elapsed time during each tensile test, in order to evaluate the thermal contribution to the microstructural changes induced during the superplastic deformation process. Moreover, the positron results were linked with the microstructural evolution of the samples followed by means of optical microscopy and Vickers microhardness technique.

  14. [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.

  15. Climate extremes can drive biological assemblages to early successional stages compared to several mild disturbances.

    PubMed

    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.

  16. 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

  17. Climate extremes can drive biological assemblages to early successional stages compared to several mild disturbances.

    PubMed

    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

  18. 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.

  19. 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. PMID:25463819

  20. The Utility of Cardiopulmonary Exercise Testing to Detect and Track Early-Stage Ischemic Heart Disease

    PubMed Central

    Chaudhry, Sundeep; Arena, Ross A.; Hansen, James E.; Lewis, Gregory D.; Myers, Jonathan N.; Sperling, Laurence S.; LaBudde, Brian D.; Wasserman, Karlman

    2010-01-01

    Evidence demonstrating the potential value of noninvasive cardiopulmonary exercise testing (CPET) to accurately detect exercise-induced myocardial ischemia is emerging. This case-based concept report describes CPET abnormalities in an asymptomatic at-risk man with suspected early-stage ischemic heart disease. When CPET was repeated 1 year after baseline assessment, his cardiovascular function had worsened, and an anti-atherosclerotic regimen was initiated. When the patient was retested after 3.3 years, the diminished left ventricular function had reversed with pharmacotherapy directed at decreasing cardiovascular events in patients with coronary artery disease. Thus, in addition to identifying appropriate patients in need of escalating therapy for atherosclerosis, CPET was useful in monitoring progression and reversal of abnormalities of the coronary circulation in a safe and cost-effective manner without the use of radiation. Serial CPET parameters may be useful to track changes marking the progression and/or regression of the underlying global ischemic burden. PMID:20884826

  1. 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.

  2. 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

  3. Detection of the early stage of recombinational DNA repair by silicon nanowire transistors.

    PubMed

    Chiesa, Marco; Cardenas, Paula P; Otón, Francisco; Martinez, Javier; Mas-Torrent, Marta; Garcia, Fernando; Alonso, Juan C; Rovira, Concepció; Garcia, Ricardo

    2012-03-14

    A silicon nanowire-based biosensor has been designed and applied for label-free and ultrasensitive detection of the early stage of recombinational DNA repair by RecA protein. Silicon nanowires transistors were fabricated by atomic force microscopy nanolithography and integrated into a microfluidic environment. The sensor operates by measuring the changes in the resistance of the nanowire as the biomolecular reactions proceed. We show that the nanoelectronic sensor can detect and differentiate several steps in the binding of RecA to a single-stranded DNA filament taking place on the nanowire-aqueous interface. We report relative changes in the resistance of 3.5% which are related to the interaction of 250 RecA·single-stranded DNA complexes. Spectroscopy data confirm the presence of the protein-DNA complexes on the functionalized silicon surfaces.

  4. Alternative to surgery in early stage NSCLC—interventional radiologic approaches

    PubMed Central

    Lee, Kyungmouk Steve

    2013-01-01

    Interventional radiologists have a variety of techniques in their armamentarium to treat pulmonary tumors. While most therapies are targeted to metastasis or palliation, percutaneous thermal ablation represents a potential therapy for not only palliation, but to treat inoperable early stage disease. Although radiofrequency ablation (RFA) is the most studied of these ablative techniques, newer technologies of thermal ablation, such as microwave and cryoablation have emerged as additional options. In this article, we will review the three different thermal ablative modalities, including patient selection, technique, outcomes, complications, and imaging follow-up. A brief discussion of state of the art techniques such as irreversible electroporation (IRE) and catheter directed therapies will also be included. PMID:25806253

  5. Production of stilbenoids and phenolic acids by the peanut plant at early stages of growth.

    PubMed

    Sobolev, Victor S; Horn, Bruce W; Potter, Thomas L; Deyrup, Stephen T; Gloer, James B

    2006-05-17

    The peanut plant (Arachis hypogaea) is known to produce stilbene phytoalexins as a defensive response to fungal invasion; however, the distribution of phytoalexins among different organs of the peanut plant at early stages of growth under axenic conditions has not been studied. Axenic plants produced a stilbenoid, resveratrol, as well as soluble bound and free phenolic acids, including 4-methoxycinnamic acid, which is reported in peanuts for the first time. Neither resveratrol nor phenolic acids were found in the root mucilage; the prenylated stilbenes were restricted to the mucilage and were not found in other organs of the peanut plant. These findings may lead to a better understanding of the defensive role of peanut stilbenes and phenolic acids.

  6. 3D simulations of the early stages of AGN jets: geometry, thermodynamics and backflow

    NASA Astrophysics Data System (ADS)

    Cielo, S.; Antonuccio-Delogu, V.; Macciò, A. V.; Romeo, A. D.; Silk, J.

    2014-04-01

    We investigate the interplay between jets from active galactic nuclei (AGNs) and the surrounding interstellar medium (ISM) through full 3D, high-resolution, adaptive mesh refinement simulations performed with the FLASH code. We follow the jet-ISM system for several Myr in its transition from an early, compact source to an extended one including a large cocoon. During the jet evolution, we identify three major evolutionary stages and we find that, contrary to the prediction of popular theoretical models, none of the simulations shows a self-similar behaviour. We also follow the evolution of the energy budget, and find that the fraction of input power deposited into the ISM (the AGN coupling constant) is of the order of a few per cent during the first few Myr. This is in broad agreement with galaxy formation models employing AGN feedback. However, we find that in these early stages, this energy is deposited only in a small fraction (<1 per cent) of the total ISM volume. Finally, we demonstrate the relevance of backflows arising within the extended cocoon generated by a relativistic AGN jet within the ISM of its host galaxy, previously proposed as a mechanism for self-regulating the gas accretion on to the central object. These backflows tend later to be destabilized by the 3D dynamics, rather than by hydrodynamic (Kelvin-Helmholtz) instabilities. Yet, in the first few hundred thousand years, backflows may create a central accretion region of significant extent, and convey there as much as a few millions of solar masses.

  7. 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. PMID:24755865

  8. 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

  9. Molecular Dynamics of Channelrhodopsin at the Early Stages of Channel Opening.

    PubMed

    Takemoto, Mizuki; Kato, Hideaki E; Koyama, Michio; Ito, Jumpei; Kamiya, Motoshi; Hayashi, Shigehiko; Maturana, Andrés D; Deisseroth, Karl; Ishitani, Ryuichiro; Nureki, Osamu

    2015-01-01

    Channelrhodopsin (ChR) is a light-gated cation channel that responds to blue light. Since ChR can be readily expressed in specific neurons to precisely control their activities by light, it has become a powerful tool in neuroscience. Although the recently solved crystal structure of a chimeric ChR, C1C2, provided the structural basis for ChR, our understanding of the molecular mechanism of ChR still remains limited. Here we performed electrophysiological analyses and all-atom molecular dynamics (MD) simulations, to investigate the importance of the intracellular and central constrictions of the ion conducting pore observed in the crystal structure of C1C2. Our electrophysiological analysis revealed that two glutamate residues, Glu122 and Glu129, in the intracellular and central constrictions, respectively, should be deprotonated in the photocycle. The simulation results suggested that the deprotonation of Glu129 in the central constriction leads to ion leakage in the ground state, and implied that the protonation of Glu129 is important for preventing ion leakage in the ground state. Moreover, we modeled the 13-cis retinal bound; i.e., activated C1C2, and performed MD simulations to investigate the conformational changes in the early stage of the photocycle. Our simulations suggested that retinal photoisomerization induces the conformational change toward channel opening, including the movements of TM6, TM7 and TM2. These insights into the dynamics of the ground states and the early photocycle stages enhance our understanding of the channel function of ChR.

  10. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy.

    PubMed

    Rajashekhar, Gangaraju; Ramadan, Ahmed; Abburi, Chandrika; Callaghan, Breedge; Traktuev, Dmitry O; Evans-Molina, Carmella; Maturi, Raj; Harris, Alon; Kern, Timothy S; March, Keith L

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved "b" wave amplitude (as measured by electroretinogram) within 1-3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. PMID:24416262

  11. Radiofrequency ablation compared to resection in early-stage hepatocellular carcinoma

    PubMed Central

    Tohme, Samer; Geller, David A.; Cardinal, Jon S.; Chen, Hui-Wei; Packiam, Vignesh; Reddy, Srinevas; Steel, Jennifer; Marsh, James W.; Tsung, Allan

    2013-01-01

    Objectives: This study aimed to compare survival outcomes after hepatic resection (HR) and radiofrequency ablation (RFA) in early-stage hepatocellular carcinoma (HCC) at a Western hepatobiliary centre. Methods: Demographic details, clinicopathologic tumour characteristics and survival outcomes were compared among non-transplant candidate patients undergoing HR (n= 50) and RFA (n= 60) for early-stage HCC during 2001–2011. Results: Patients who underwent HR had larger tumours, a longer length of stay and a higher rate of postoperative complications. After a median follow-up of 29 months, there were no significant differences between the treatment groups in 1-, 3- and 5-year overall survival (OS) [RFA group: 86%, 50%, 35%, respectively; HR group: 88%, 68%, 47%, respectively (P= 0.222)] or disease-free survival (DFS) [RFA group: 68%, 42%, 28%, respectively; HR group: 66%, 42%, 34%, respectively (P= 0.823)]. The 58 patients who underwent RFA demonstrated ablation success on follow-up computed tomography at 3 months. Of these, 96.5% of patients showed sustained ablation success over the entire follow-up period. In a subgroup analysis of patients with tumours measuring 2–5 cm, no differences in OS or DFS emerged between the HR and RFA groups. Similarly, no significant differences in outcomes in patients with Child–Pugh class A cirrhosis were seen between the RFA and HR groups. Conclusions: Radiofrequency ablation is comparable with HR in terms of OS and DFS. It is a reasonable alternative as a first-line treatment for HCC in well-selected patients who are not candidates for transplant. PMID:23374361

  12. Ocean warming alters cellular metabolism and induces mortality in fish early life stages: A proteomic approach.

    PubMed

    Madeira, D; Araújo, J E; Vitorino, R; Capelo, J L; Vinagre, C; Diniz, M S

    2016-07-01

    Climate change has pervasive effects on marine ecosystems, altering biodiversity patterns, abundance and distribution of species, biological interactions, phenology, and organisms' physiology, performance and fitness. Fish early life stages have narrow thermal windows and are thus more vulnerable to further changes in water temperature. The aim of this study was to address the sensitivity and underlying molecular changes of larvae of a key fisheries species, the sea bream Sparus aurata, towards ocean warming. Larvae were exposed to three temperatures: 18°C (control), 24°C (warm) and 30°C (heat wave) for seven days. At the end of the assay, i) survival curves were plotted for each temperature treatment and ii) entire larvae were collected for proteomic analysis via 2D gel electrophoresis, image analysis and mass spectrometry. Survival decreased with increasing temperature, with no larvae surviving at 30°C. Therefore, proteomic analysis was only carried out for 18°C and 24°C. Larvae up-regulated protein folding and degradation, cytoskeletal re-organization, transcriptional regulation and the growth hormone while mostly down-regulating cargo transporting and porphyrin metabolism upon exposure to heat stress. No changes were detected in proteins related to energetic metabolism suggesting that larval fish may not have the energetic plasticity needed to sustain cellular protection in the long-term. These results indicate that despite proteome modulation, S. aurata larvae do not seem able to fully acclimate to higher temperatures as shown by the low survival rates. Consequently, elevated temperatures seem to have bottleneck effects during fish early life stages, and future ocean warming can potentially compromise recruitment's success of key fisheries species. PMID:27062348

  13. 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.

  14. 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.

  15. 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

  16. Neurotherapeutic Effects of Pueraria mirifica Extract in Early- and Late-Stage Cognitive Impaired Rats.

    PubMed

    Anukulthanakorn, Kanya; Parhar, Ishwar S; Jaroenporn, Sukanya; Kitahashi, Takashi; Watanbe, Gen; Malaivijitnond, Suchinda

    2016-06-01

    We determined the neurotherapeutic effects of Pueraria mirifica extract (PME) and pure puerarin (PU) in comparison with 17β-estradiol (E2 ) in early- and late-stage cognitive impaired rats. Rats were ovariectomized (OVX), kept for 2 and 4 months to induce early- and late-stage cognitive impairment, respectively, and divided into four groups that were treated daily with (i) distilled water, (ii) 100 mg/kg of PME, (iii) 7 mg/kg of PU, and (iv) 80 µg/kg of E2 for 4 months. The estrogen deficiency symptoms of OVX rats were abrogated by treatment with E2 or PME, but not by treatment with PU. The mRNA level of genes associated with amyloid production (App and Bace1) and hyperphosphorylated Tau (Tau4) were upregulated together with the level of impaired cognition in the 2- and 4-month OVX rats. Treatment with E2 reduced the level of cognitive impairment more than that with PME and PU, and 2-month OVX rats were more responsive than 4-month OVX rats. All treatments down-regulated the Bace1 mRNA level in 2-month OVX rats, while PU and PME also decreased the App mRNA level in 2- and 4-month OVX rats, respectively. Only PU suppressed Tau4 expression in 2-month OVX rats. Thus, PME and PU elicit neurotherapeutic effects in different pathways, and earlier treatment is optimal. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26915634

  17. Regenerative Therapeutic Potential of Adipose Stromal Cells in Early Stage Diabetic Retinopathy

    PubMed Central

    Rajashekhar, Gangaraju; Ramadan, Ahmed; Abburi, Chandrika; Callaghan, Breedge; Traktuev, Dmitry O.; Evans-Molina, Carmella; Maturi, Raj; Harris, Alon; Kern, Timothy S.; March, Keith L.

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved “b” wave amplitude (as measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. PMID:24416262

  18. 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

  19. Early stage biomineralization in the periostracum of the 'living fossil' bivalve Neotrigonia.

    PubMed

    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 understanding of

  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. PMID:25261407

  1. Chronic effects of acetone on the fathead minnow (Pimephales promelas) during early life-stage development

    SciTech Connect

    Mank, M.; Swigert, J.

    1995-12-31

    A 28-day post-hatch early life-stage development toxicity test was conducted to determine the chronic effects of acetone on the fathead minnow (Pimephales promelas). In this study, less than 24-hour old fathead minnow embryos were exposed to 0.25, 0.50, 1.0, 2.0, and 4.0 mL acetone/L and a negative control for a 4-day pre-hatch period and 28 days following hatch. During the pre-hatch period, no adverse effects on embryo survival or hatching success were observed in any of the treatment groups tested when compared to the negative control. From completion of matching to test termination, fathead minnows exposed to 4.0 mL acetone/L, experienced reduced survival, a statistically significant reduction in growth and impairment of critical behavioral functions when compared to the negative control group. Growth of fathead minnows exposed to 2.0 mL acetone/L also experienced a statistically significant effect upon growth when compared to the negative control, however, survival and behavior were not affected during the post-hatch period. Survival, growth, and behavior of fathead minnows exposed to 0.25, 0.50, and 1.0 mL acetone/L from hatching to test termination was comparable to the control group. The no observed effect concentration (NOEC) for fathead minnows exposed to acetone during early life-stage development was 1.0 mL acetone/L, and the lowest observed effect concentration (LOEC) was 2.0 mL acetone/L. The maximum acceptable toxicant concentration (MATC) was calculated to be 1.4 mL acetone/L.

  2. Electrolyte-carbohydrate beverage prevents water loss in the early stage of high altitude training.

    PubMed

    Yanagisawa, Kae; Ito, Osamu; Nagai, Satsuki; Onishi, Shohei

    2012-01-01

    To prevent water loss in the early stage of high altitude training, we focused on the effect of electrolyte-carbohydrate beverage (EC). Subjects were 16 male university students who belonged to a ski club. They had ski training at an altitude of 1,800 m. The water (WT) group drank only water, and the EC group drank only an electrolyte-carbohydrate beverage. They arrived at the training site in the late afternoon. The study started at 7 pm on the day of arrival and continued until noon of the 4(th) day. In the first 12 hours, 1 L of beverages were given. On the second and third days, 2.5 L of beverages were given. All subjects ate the same meals. Each morning while in fasting condition, subjects were weighed and blood was withdrawn for various parameters (hemoglobin, hematocrit, sodium, potassium and aldosterone). Urine was collected at 12 hour intervals for a total 60 hours (5 times). The urine volume, gravity, sodium and potassium concentrations were measured. Peripheral oxygen saturation and heart rate were measured during sleep with a pulse oximeter. Liquid intakes in both groups were similar, hence the electrolytes intake was higher in the EC group than in the WT group. The total urine volume was lower in the EC group than in the WT group, respectively (p<0.05). Plasma volume decreased in the WT group and increased in the EC group but a significant difference was not observed in the final value. Aldosterone concentration tended to be less in the EC group than in the WT group. Electrolyte-carbohydrate beverage in the early stage of high altitude training may be effective in decreasing urinary output and preventing loss of blood plasma volume.

  3. 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

  4. 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.

  5. Dendritic cell appearance and differentiation during early and late stages of rat stomach carcinogenesis.

    PubMed

    Takeuchi, Motoi; Yamamoto, Masami; Tatematsu, Masae; Miki, Kazumasa; Sakaki, Yoshiyuki; Furihata, Chie

    2002-08-01

    Dendritic cell appearance and differentiation during early and late stages of rat stomach carcinogenesis were studied in the pyloric mucosa. Young male rats were given drinking water with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; 100 mg/liter) for 14 days. Use of competitive RT-PCR and northern blotting showed that MNNG exposure induced 3- to 4-fold greater expression of the genes for integrin beta7 and integrin alphaE2 (identical with antigen OX-62, a dendritic cell marker), as well as three cytokines, IL-4, GM-CSF and TNFalpha, in the stomach pyloric mucosa of resistant Buffalo rats compared to sensitive ACI rats. These genes were minimally expressed in control animals. The results confirm the appearance of dendritic cells in the target pyloric mucosa and suggest the possibility that dendritic cell differentiation and maturation are induced by various cytokines, at least in Buffalo rats. Competitive RT-PCR showed expression of integrin alphaE2 and beta7, MHC class II-associated invariant chain (Ii), MHC class II, B7-1, CD28, GM-CSF and TNFalpha genes in all 12 examined stomach adenocarcinomas and adenomas induced in male Lewis and WKY rats with 30 weeks' MNNG exposure, suggesting the presence of dendritic cells in tumors. OX-62 staining and western blotting for OX-62 also confirmed the presence of dendritic cells in tumors. However, the population of dendritic cells in tumors was less than that in the pyloric mucosa after 14 days' MNNG exposure. The present results suggest that immune defense involving dendritic cells is marshaled from the very early initiation stage during rat stomach cancer development, but is downgraded in developed tumors.

  6. Total abdominal and pelvic radiotherapy in the management of early stage ovarian carcinoma

    SciTech Connect

    Macbeth, F.R.; Macdonald, H.; Williams, C.J.

    1988-08-01

    In a prospective study, 57 women with early stage ovarian carcinoma received total abdominal and pelvic radiotherapy (TAPR) following radical surgery. The whole abdomen received 22.5 Gy m.p.d. by large opposed fields in 18 fractions over 4 1/2 weeks, with 8 MeV X rays, followed by a further 22.5 Gy in 10 fractions over 2 weeks to the pelvis alone, using a dosage and technique similar to that described from the Princess Margaret Hospital, Toronto. The actuarial 5-year relapse-free and overall survival figures were 49 and 57% respectively, which appear to be significantly worse than those reported from Toronto (73% and 75%). The incidence of severe bowel toxicity (7%) was higher. There was no correlation between survival and FIGO stage at laparotomy, but a significant correlation with histological grade. These data do not seem to support the idea of a curative role for post-operative irradiation at this dosage in these patients.

  7. Part 2: Potencies and interactions of polybrominated aromatic hydrocarbons in rainbow trout early life stage mortality

    SciTech Connect

    Hornung, M.W.; Zabel, E.W.; Peterson, R.E.; Bergman, A.; Safe, S.

    1994-12-31

    Polybrominated biphenyls (PBBs), dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs), and diphenylethers (PBDPES) in aquatic environments may pose a risk to fish early life stage survival. Following rainbow trout egg microinjection, the potencies of these polybrominated aromatic hydrocarbons were determined using fish specific toxic equivalency factors (TEFs). TEFs are defined as the ratio of TCDD LD{sub 50} to brominated congener LD{sub 50}. Sac fry stage specific TCDD like toxicity included yolk sac edema, pericardial edema, multifocal hemorrhages and craniofacial malformations. TEFs of active congeners were: 2,3,7,8-TBDF = 0.23; 2,3,4,7,8-PBDF = 0.069; 1,2,3,4,7,8-HxBDD = 0.009. No signs of toxicity with 2,2{prime},4,4{prime}-TBDPE, 2,2{prime},3,4,4{prime}-PBDPE, or 2,2{prime},4,4{prime},5-PBDPE occurred at egg concentrations up to 126,37 {mu}g/g. Since these congeners occur as complex mixtures, the potential for additive, antagonistic, or synergistic interactions must also be determined for accurate risk assessment. Graded doses of 2,3,7,8-TBDD or 1,2,3,7,8-PBDD alone, or graded doses of fixed ratios of the two congeners were injected into newly fertilized rainbow trout eggs. Separate dose response curves were determined for each ratio and each individual congener. Isobolographic analysis supports the hypothesis that these congeners act additively.

  8. Laser plasma plume structure and dynamics in the ambient air: The early stage of expansion

    SciTech Connect

    Cirisan, M.; Jouvard, J. M.; Lavisse, L.; Hallo, L.; Oltra, R.

    2011-05-15

    Laser ablation plasma plume expanding into the ambient atmosphere may be an efficient way to produce nanoparticles. From that reason it would be interesting to study the properties of these laser induced plasmas formed under conditions that are known to be favorable for nanoparticles production. In general, plume behavior can be described as a two-stage process: a 'violent' plume expansion due to the absorption of the laser beam energy (during the laser pulse) followed by a fast adiabatic expansion in the ambient gas (after the end of the laser pulse). Plasma plume may last a few microseconds and may have densities 10{sup -6} times lower than the solid densities at temperatures close to the ambient temperature. Expansion of the plasma plume induced by the impact of a nanosecond laser beam ({lambda} 1064 nm) on the surface of metallic samples in the open air has been investigated by means of fast photography. Spatio-temporal evolution of the plume at the early stage of its expansion (first 330 ns) has been recorded. Structure and dynamics of the plasma plume have been investigated and compared to numerical simulations obtained with a hydro-code, as well as some scaling laws. In addition, measurements using different sample materials (Al, Fe, and Ti) have been performed in order to analyze the influence of target material on plume expansion.

  9. Ectomycorrhizin Synthesis and Polypeptide Changes during the Early Stage of Eucalypt Mycorrhiza Development 1

    PubMed Central

    Hilbert, Jean-Louis; Costa, Guy; Martin, Francis

    1991-01-01

    In functioning eucalypt ectomycorrhizas, biochemical alterations are accompanied by a differential accumulation of polypeptides including the synthesis of symbiosis-related proteins (JL Hilbert, Martin FM [1988] New Phytol 110: 339-346). In the present study, protein biosynthesis in the early stages of ectomycorrhiza formation on Eucalyptus globulus subsp. bicostata Kirkp. was examined using compatible and incompatible isolates of the basidiomycete Pisolithus tinctorius (Coker & Couch). Changes in polypeptide composition were observed within hours following contact of the compatible mycelium with the roots, well before the differentiation of typical symbiotic tissues. At this stage, at least seven symbiosis-related proteins (ectomycorrhizins) accumulated in root tissues. In vivo incorporation of [35S]methionine by ectomycorrhizas followed by electrophoresis of the labeled proteins revealed that most of these differences in polypeptide concentrations, including the ectomycorrhizin accumulation, are the result of differential protein biosynthesis rather than posttranslational modifications of the polypeptides. The initial development of eucalypt ectomycorrhizas, therefore, coincides with the synthesis of symbiosis-related proteins and the data presented here provide essential evidence to ascribe a functional developmental role to these proteins. ImagesFigure 2Figure 3Figure 4Figure 5 PMID:16668539

  10. Do Hospital Characteristics Influence Cancer-Specific Survival for Early Stage Lung Cancer?

    PubMed Central

    David, Elizabeth A; Chen, Yingjia; Cooke, David T; Perry, Andrew; Canter, Robert J; Cress, Rosemary

    2015-01-01

    Background Quality of oncologic outcomes is of paramount importance in the care of patients with non-small cell lung cancer (NSCLC). We sought to evaluate the relationship of hospital volume for lobectomy on cancer-specific survival in NSCLC patients treated in California, as well as the influence of Committee on Cancer (CoC) accreditation. Methods The California Cancer Registry was queried from 2004–2011 for cases of Stage I NSCLC and 8,345 patients were identified. Statistical analysis was used to determine prognostic factors for cancer-specific survival. Results 7,587 patients were treated surgically. CoC accreditation was not significant for cancer-specific survival, but treatment in high volume centers was associated with longer survival when compared to low and medium volume centers (HR 1.77, 1.474–2.141 and HR 1.23, 1.058–1.438). Conclusions These data suggest that surgical treatment in high volume hospitals is associated with longer cancer-specific survival for early-stage NSCLC, but that CoC accreditation is not. PMID:26193801

  11. Modeling bacterial attachment to surfaces as an early stage of biofilm development.

    PubMed

    El Moustaid, Fadoua; Eladdadi, Amina; Uys, Lafras

    2013-06-01

    Biofilms are present in all natural, medical and industrial surroundings where bacteria live. Biofilm formation is a key factor in the growth and transport of both beneficial and harmful bacteria. While much is known about the later stages of biofilm formation, less is known about its initiation which is an important first step in the biofilm formation. In this paper, we develop a non-linear system of partial differential equations of Keller-Segel type model in one-dimensional space, which couples the dynamics of bacterial movement to that of the sensing molecules. In this case, bacteria perform a biased random walk towards the sensing molecules. We derive the boundary conditions of the adhesion of bacteria to a surface using zero-Dirichlet boundary conditions, while the equation describing sensing molecules at the interface needed particular conditions to be set. The numerical results show the profile of bacteria within the space and the time evolution of the density within the free-space and on the surface. Testing different parameter values indicate that significant amount of sensing molecules present on the surface leads to a faster bacterial movement toward the surface which is the first step of biofilm initiation. Our work gives rise to results that agree with the biological description of the early stages of biofilm formation. PMID:23906151

  12. Phenolic compounds of 'Galega Vulgar' and 'Cobrançosa' olive oils along early ripening stages.

    PubMed

    Peres, Fátima; Martins, Luisa L; Mourato, Miguel; Vitorino, Conceição; Antunes, Paulo; Ferreira-Dias, Suzana

    2016-11-15

    In this study, the lipophilic and hydrophilic phenol composition of virgin olive oils (VOO) obtained from olives from two of the most important Portuguese cultivars ('Galega Vulgar' and 'Cobrançosa'), harvested at different ripening stages and under two irrigation schemes (rain fed and irrigated), was evaluated. Phenolic alcohols (hydroxytyrosol and tyrosol), phenolic acids and derivatives and flavonoids (luteolin and apigenin), as well as tocopherols were quantified. Lipophilic (>300mgkg(-1)) and hydrophilic phenols (>600mgkg(-1)) were present in high contents in both VOO, for early ripening stages. Gamma-tocopherol content is higher in 'Galega Vulgar' VOO. Total phenols showed a decrease between ripening index 2.5 and 3.5. The dialdehydic form of elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA), also known as oleacein, was the major phenolic compound identified in both oils. The concentration of free hydroxytyrosol and tyrosol in both VOO is very low while their esterified derivatives, like 3,4-DHPEA-EDA and p-HPEA-EDA, are much more abundant. PMID:27283606

  13. In situ nanomechanical characterization of the early stages of swelling and degradation of a biodegradable polymer.

    PubMed

    Dumitru, A C; Espinosa, F M; Garcia, R; Foschi, G; Tortorella, S; Valle, F; Dallavalle, M; Zerbetto, F; Biscarini, F

    2015-03-12

    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.

  14. 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

  15. Phenolic compounds of 'Galega Vulgar' and 'Cobrançosa' olive oils along early ripening stages.

    PubMed

    Peres, Fátima; Martins, Luisa L; Mourato, Miguel; Vitorino, Conceição; Antunes, Paulo; Ferreira-Dias, Suzana

    2016-11-15

    In this study, the lipophilic and hydrophilic phenol composition of virgin olive oils (VOO) obtained from olives from two of the most important Portuguese cultivars ('Galega Vulgar' and 'Cobrançosa'), harvested at different ripening stages and under two irrigation schemes (rain fed and irrigated), was evaluated. Phenolic alcohols (hydroxytyrosol and tyrosol), phenolic acids and derivatives and flavonoids (luteolin and apigenin), as well as tocopherols were quantified. Lipophilic (>300mgkg(-1)) and hydrophilic phenols (>600mgkg(-1)) were present in high contents in both VOO, for early ripening stages. Gamma-tocopherol content is higher in 'Galega Vulgar' VOO. Total phenols showed a decrease between ripening index 2.5 and 3.5. The dialdehydic form of elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA), also known as oleacein, was the major phenolic compound identified in both oils. The concentration of free hydroxytyrosol and tyrosol in both VOO is very low while their esterified derivatives, like 3,4-DHPEA-EDA and p-HPEA-EDA, are much more abundant.

  16. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    PubMed

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-01

    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.

  17. Studying early stages of fibronectin fibrillogenesis in living cells by atomic force microscopy

    PubMed Central

    Gudzenko, Tetyana; Franz, Clemens M.

    2015-01-01

    Fibronectin (FN) is an extracellular matrix protein that can be assembled by cells into large fibrillar networks, but the dynamics of FN remodeling and the transition through intermediate fibrillar stages are incompletely understood. Here we used a combination of fluorescence microscopy and time-lapse atomic force microscopy (AFM) to visualize initial stages of FN fibrillogenesis in living fibroblasts at high resolution. Initial FN nanofibrils form within <5 min of cell–matrix contact and subsequently extend at a rate of 0.25 μm/min at sites of cell membrane retraction. FN nanofibrils display a complex linear array of globular features spaced at varying distances, indicating the coexistence of different conformational states within the fibril. In some cases, initial fibrils extended in discrete increments of ∼800 nm during a series of cyclical membrane retractions, indicating a stepwise fibrillar extension mechanism. In presence of Mn2+, a known activator of integrin adhesion to FN, fibrillogenesis was accelerated almost threefold to 0.68 μm/min and fibrillar dimensions were increased, underlining the importance of integrin activation for early FN fibrillogenesis. FN fibrillogenesis visualized by time-lapse AFM thus provides new structural and mechanistic insight into initial steps of cell-driven FN fibrillogenesis. PMID:26371081

  18. 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.

  19. Robotic-Assisted Thoracic Surgery for Early-Stage Lung Cancer: A Review.

    PubMed

    Brooks, Paula

    2015-07-01

    This review evaluates the benefits and disadvantages associated with the use of robotic-assisted technology in performing lobectomies in patients with early-stage lung cancer. The author conducted a literature search of Ovid®, MEDLINE®, PubMed®, and CINAHL® for articles published from 2005 to 2013. Search criteria included key terms such as robot, robotic, robotic-assisted lobectomy, and lung cancer. Of 922 articles, the author included a total of 12 research-based published studies in the analysis and incorporated the findings into an evidence table. Results showed that robotic-assisted lobectomies are feasible safe procedures for patients with stage 1A or 1B lung cancer; however, there is a steep learning curve and long-term randomized studies evaluating robotic-assisted lobectomy and conventional posterolateral thoracotomy or video-assisted thoracic lobectomy are needed. For patient safety, perioperative nurses should be aware of the length of time and experience required to perform these procedures, the costs, techniques, benefits, and disadvantages.

  20. Lethal toxicity of industrial chemicals to early life stages of Tilapia guineensis.

    PubMed

    Ezemonye, L I N; Ogeleka, D F; Okieimen, F E

    2008-08-30

    The toxic effects of industrial chemicals on three early life stages of an economically important fish, Tilapia guineensis were investigated using the Organisation for Economic Cooperation and Development (OECD) # 203 recommended semi-static renewal bioassay. The assessment was necessary for the uncontrollable disposal of Neatex (liquid detergent) and Norust CR 486 (corrosion inhibitor) into the Niger Delta environment of Nigeria. The estimated 96-h LC(50) for 7-, 14- and 28-day-old fish in Norust CR 486 exposure was considered "more toxic" than Neatex in all life stages and was dependent on species age, exposure duration and environment. In the fresh water test, for Neatex and Norust CR 486 exposures for day 7, 14 and 28, the 96-h LC50 were 8.79, 17.10 and 82.42 mg/l and 5.55, 13.58 and 20.21 mg/l, respectively. In the brackish test, 15.42 and 46.52 mg/l, not determined (ND) and 7.35, 13.95 and 24.50mg/l were obtained. Differential toxicity was observed in the fresh and brackish water fish for the two chemicals and controls at p<0.05. The high sensitivity of the 7-day-old test organisms to both chemicals provides a rationale for regulatory surveillance and monitoring of both chemicals in the fragile Niger Delta environment. PMID:18262353

  1. 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.

  2. Modeling TGF-β in Early Stages of Cancer Tissue Dynamics

    PubMed Central

    Ascolani, Gianluca; Liò, Pietro

    2014-01-01

    Recent works have highlighted a double role for the Transforming Growth Factor (-): it inhibits cancer in healthy cells and potentiates tumor progression during late stage of tumorigenicity, respectively; therefore it has been termed the “Jekyll and Hyde” of cancer or, alternatively, an “excellent servant but a bad master”. It remains unclear how this molecule could have the two opposite behaviours. In this work, we propose a - multi scale mathematical model at molecular, cellular and tissue scales. The multi scalar behaviours of the - are described by three coupled models built up together which can approximatively be related to distinct microscopic, mesoscopic, and macroscopic scales, respectively. We first model the dynamics of - at the single-cell level by taking into account the intracellular and extracellular balance and the autocrine and paracrine behaviour of -. Then we use the average estimates of the - from the first model to understand its dynamics in a model of duct breast tissue. Although the cellular model and the tissue model describe phenomena at different time scales, their cumulative dynamics explain the changes in the role of - in the progression from healthy to pre-tumoral to cancer. We estimate various parameters by using available gene expression datasets. Despite the fact that our model does not describe an explicit tissue geometry, it provides quantitative inference on the stage and progression of breast cancer tissue invasion that could be compared with epidemiological data in literature. Finally in the last model, we investigated the invasion of breast cancer cells in the bone niches and the subsequent disregulation of bone remodeling processes. The bone model provides an effective description of the bone dynamics in healthy and early stages cancer conditions and offers an evolutionary ecological perspective of the dynamics of the competition between cancer and healthy cells. PMID:24586338

  3. 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…

  4. Small pelagics in a changing ocean: biological responses of sardine early stages to warming.

    PubMed

    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 (Q 10 = 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

  5. 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

    2016-04-01

    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

  6. [The psychopathological pictures of the early stages of dementia syndromes (vasogenic and of Alzheimer's type)].

    PubMed

    Bidzan, L

    1998-01-01

    The goal of the research is to determine the early symptoms predicting dementia syndromes both Vasogenic and Alzheimer type. The investigations covered: 36 people without any psychopathological syndrome, 32 people with dementia of Alzheimer type and 36 people with vasogenic dementia. DSM IV criteria were accepted as a basis for recognition of dementia syndromes. The qualified patients underwent basic examination consisting of the following elements: AMDP scale (the estimation of psychic and somatic condition), Global Scale of Dementia, Hachinski scale, Blessed scale, Folsteins scale (MMS), Instrumental Activities of Daily Living, Physical self Maintenance Scale and two methods of the authors: Current Events Card and Prodromal Symptoms Card. On the basis of examinations the following conclusions can be stated:--persons in early stages of dementia differ from those without any symptoms of it by the occurrence of many psychopathological symptoms--not only connected with the cognitive sphere;--in the period preceding the development of dementia the frequency of occurrence of some symptoms is different according to etiology of the process (Alzheimer or vasogenic);--the applied clinical scales differ significantly in their value for the diagnosis and the estimation of intensification of dementia processes. PMID:9920996

  7. 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

  8. 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

  9. 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

  10. Timing and extent of early marine oxygen isotope stage 2 alpine glaciation in Skagit Valley, Washington

    NASA Astrophysics Data System (ADS)

    Riedel, Jon L.; Clague, John J.; Ward, Brent C.

    2010-03-01

    Twenty-two new radiocarbon ages from Skagit valley provide a detailed chronology of alpine glaciation during the Evans Creek stade of the Fraser Glaciation (early marine oxygen isotope stage (MIS) 2) in the Cascade Range, Washington State. Sediments at sites near Concrete, Washington, record two advances of the Baker valley glacier between ca. 30.3 and 19.5 cal ka BP, with an intervening period of glacier recession about 24.9 cal ka BP. The Baker valley glacier dammed lower Skagit valley, creating glacial Lake Concrete, which discharged around the ice dam along Finney Creek, or south into the Sauk valley. Sediments along the shores of Ross Lake in upper Skagit valley accumulated in glacial Lake Skymo after ca. 28.7 cal ka BP behind a glacier flowing out of Big Beaver valley. Horizontally laminated silt and bedded sand and gravel up to 20 m thick record as much as 8000 yr of deposition in these glacially dammed lakes. The data indicate that alpine glaciers in Skagit valley were far less extensive than previously thought. Alpine glaciers remained in advanced positions for much of the Evans Creek stade, which may have ended as early as 20.8 cal ka BP.

  11. Proton therapy for early stage prostate cancer: is there a case?

    PubMed

    Chan, Tabitha Y; Tan, Poh Wee; Tang, Johann I

    2016-01-01

    Proton-beam therapy (PBT) for prostate cancer has been in used for several decades, with its technique evolving significantly over this period. A growing number of centers now routinely utilize pencil-beam scanning as an advanced technique of PBT. Interest and controversy concerning its use have recently come under scrutiny. While the past decade has produced an assemblage of evidence suggesting that PBT is safe and effective for early stage prostate cancer, it is still unknown whether the theoretical dosimetric advantages of PBT translate into meaningful clinical improvements over routine intensity-modulated radiation therapy, which is commonly used for these patients. Outcomes from early trials using whole courses of PBT have shown mixed results when compared with routine intensity-modulated radiation therapy. Therefore, randomized trials comparing these two techniques should be undertaken, as this would help in defining the role of PBT for this patient group. This article aims to describe the basics of PBT, review the reasons for the growing interest in PBT, review the evidence for PBT, review the controversy surrounding PBT, and inquire about PBT's future in the treatment of prostate cancer, with attention to its physical properties, comparative clinical and cost-effectiveness, and advances in its delivery. PMID:27672328

  12. 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

  13. Affective systems induce formal thought disorder in early-stage psychosis.

    PubMed

    Minor, Kyle S; Marggraf, Matthew P; Davis, Beshaun J; Mehdiyoun, Nicole F; Breier, Alan

    2016-05-01

    Although formal thought disorder (FTD) has been described since early conceptualizations of psychosis, its underlying mechanisms are unclear. Evidence suggests FTD may be influenced by affective and cognitive systems; however, few have examined these relationships-with none focusing on early-stage psychosis (EP). In this study, positive FTD and speech production were measured in sex- and race-matched EP (n = 19) and healthy control (n = 19) groups by assessing "reactivity"-a change in experimental compared with baseline conditions-across baseline, affective, and cognitive conditions. Relationships with functioning were also examined within each group. Three key findings emerged: (a) the EP group displayed large differences in positive FTD and speech production, (b) those with EP exhibited affective reactivity for positive FTD, and (c) positive FTD and affective reactivity were linked with poor real-world functioning in EP and these relationships did not considerably change when controlling for positive symptom (e.g., delusions, hallucinations) severity. Our findings provide preliminary evidence that affective, but not cognitive, systems play a critical role in positive FTD. Affective reactivity, in particular, may aid in predicting those with EP who go on to develop serious social impairments. Future work should focus on whether affective systems differentially influence those at separate points on the psychosis-spectrum in an effort to establish evidence-based treatments for FTD. (PsycINFO Database Record PMID:26999283

  14. 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.

  15. Proton therapy for early stage prostate cancer: is there a case?

    PubMed Central

    Chan, Tabitha Y; Tan, Poh Wee; Tang, Johann I

    2016-01-01

    Proton-beam therapy (PBT) for prostate cancer has been in used for several decades, with its technique evolving significantly over this period. A growing number of centers now routinely utilize pencil-beam scanning as an advanced technique of PBT. Interest and controversy concerning its use have recently come under scrutiny. While the past decade has produced an assemblage of evidence suggesting that PBT is safe and effective for early stage prostate cancer, it is still unknown whether the theoretical dosimetric advantages of PBT translate into meaningful clinical improvements over routine intensity-modulated radiation therapy, which is commonly used for these patients. Outcomes from early trials using whole courses of PBT have shown mixed results when compared with routine intensity-modulated radiation therapy. Therefore, randomized trials comparing these two techniques should be undertaken, as this would help in defining the role of PBT for this patient group. This article aims to describe the basics of PBT, review the reasons for the growing interest in PBT, review the evidence for PBT, review the controversy surrounding PBT, and inquire about PBT’s future in the treatment of prostate cancer, with attention to its physical properties, comparative clinical and cost-effectiveness, and advances in its delivery.

  16. 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.

  17. Social exclusion and early-stage interpersonal perception: selective attention to signs of acceptance.

    PubMed

    Dewall, C Nathan; Maner, Jon K; Rouby, D Aaron

    2009-04-01

    Social exclusion can thwart people's powerful need for social belonging. Whereas prior studies have focused primarily on how social exclusion influences complex and cognitively downstream social outcomes (e.g., memory, overt social judgments and behavior), the current research examined basic, early-in-the-cognitive-stream consequences of exclusion. Across 4 experiments, the threat of exclusion increased selective attention to smiling faces, reflecting an attunement to signs of social acceptance. Compared with nonexcluded participants, participants who experienced the threat of exclusion were faster to identify smiling faces within a "crowd" of discrepant faces (Experiment 1), fixated more of their attention on smiling faces in eye-tracking tasks (Experiments 2 and 3), and were slower to disengage their attention from smiling faces in a visual cueing experiment (Experiment 4). These attentional attunements were specific to positive, social targets. Excluded participants did not show heightened attention to faces conveying social disapproval or to positive nonsocial images. The threat of social exclusion motivates people to connect with sources of acceptance, which is manifested not only in "downstream" choices and behaviors but also at the level of basic, early-stage perceptual processing. PMID:19309198

  18. Proton therapy for early stage prostate cancer: is there a case?

    PubMed Central

    Chan, Tabitha Y; Tan, Poh Wee; Tang, Johann I

    2016-01-01

    Proton-beam therapy (PBT) for prostate cancer has been in used for several decades, with its technique evolving significantly over this period. A growing number of centers now routinely utilize pencil-beam scanning as an advanced technique of PBT. Interest and controversy concerning its use have recently come under scrutiny. While the past decade has produced an assemblage of evidence suggesting that PBT is safe and effective for early stage prostate cancer, it is still unknown whether the theoretical dosimetric advantages of PBT translate into meaningful clinical improvements over routine intensity-modulated radiation therapy, which is commonly used for these patients. Outcomes from early trials using whole courses of PBT have shown mixed results when compared with routine intensity-modulated radiation therapy. Therefore, randomized trials comparing these two techniques should be undertaken, as this would help in defining the role of PBT for this patient group. This article aims to describe the basics of PBT, review the reasons for the growing interest in PBT, review the evidence for PBT, review the controversy surrounding PBT, and inquire about PBT’s future in the treatment of prostate cancer, with attention to its physical properties, comparative clinical and cost-effectiveness, and advances in its delivery. PMID:27672328

  19. The Role of Endoscopic Ultrasonography in T Staging: Early Gastric Cancer and Esophageal Cancer

    PubMed Central

    2013-01-01

    While a number of diagnostic methods have been developed, endoscopic ultrasound (EUS) still takes the most important role in the preoperative evaluation of esophageal cancer. EUS can detect lesions of all esophageal cancer and can accurately perform T staging. In a recent meta-analysis of EUS in esophageal cancer, the sensitivity and specificity of EUS on esophageal cancer were 81.6% and 99.4% in T1, 81.4% and 96.3% in T2, 91.4% and 94.4% in T3, and 92.4% and 97.4% in T4, respectively. The use of EUS can reduce unnecessary surgeries and lead to apply proper treatments to patients. The advance of endoscopic submucosal dissection have necessitated the presurgical detection of early cancer lesions without lymph node metastasis. Understanding the practical meanings of images shown by EUS is important to decide patients for whom endoscopic treatments can be effective. In early gastric cancer, EUS can accurately predict mucosal and SM1 (invasion into the submucosal layer of less than 500 µm from muscularis mucosa) lesions, which are considered as good indications for endoscopic treatments. PMID:23767033

  20. 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

  1. 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

  2. Regulation of cap-dependent translation initiation in the early stage porcine parthenotes.

    PubMed

    Susor, Andrej; Jelínková, Lucie; Karabínová, Pavla; Torner, Helmut; Tomek, Wolfgang; Kovárová, Hana; Kubelka, Michal

    2008-12-01

    The binding of mRNAs to ribosomes is mediated by the protein complex eIF4F in conjunction with eIF4B (eukaryotic initiation factor 4F and 4B). EIF4F is a three subunit complex consisting of eIF4A (RNA helicase), eIF4E (mRNA cap binding protein), and eIF4G (bridging protein). The crucial role is played by eIF4E, which directly binds the 5'-cap structure of the mRNA and facilitates the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. EIF4E binding to mRNA and to other initiation factors is regulated on several levels, including its phosphorylation on Ser-209, and association with its regulatory protein 4E-binding protein (4E-BP1). In this study we document that both the translation initiation factor eIF4E and its regulator 4E-BP1 become dephosphorylated in the early stage porcine zygotes already 8 hr post-activation. Similarly, the activities of ERK1/2 MAP and Mnk1 kinases, which are both involved in eIF4E phosphorylation, gradually decrease during this period with the timing similar to that of eIF4E dephosphorylation. The formation of an active eIF4F complex is also diminished after 9-15 hr post-activation, although substantial amounts of this complex have been detected also 24 hr post-activation (2-cell stage). The overall protein synthesis in the parthenotes decreases gradually from 12 hr post-activation reaching a minimum after 48 hr (4-cell stage). Although the translation is gradually decreasing during early preimplantation development, the eIF4F complex, which is temporarily formed, might be a premise for the translation of a small subset of mRNAs at this period of development.

  3. 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.

  4. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle.

    PubMed Central

    Shirazi, Y; Pitha, P M

    1992-01-01

    In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages. Images PMID:1738192

  5. Upgrading the definition of early gastric cancer: better staging means more appropriate treatment

    PubMed Central

    Saragoni, Luca

    2015-01-01

    Since Murakami defined early gastric cancer (EGC) as a “carcinoma limited to the gastric mucosa and/or submucosa regardless of the lymph node status”, several authors have focused on the most influential histopathological parameters for predicting the development of lymph node metastases by considering the lymph node status as an important prognostic factor. A few authors have also considered the depth of invasion as one of the keys to explaining the existence of subgroups of patients affected by EGC with poor prognoses. In any case, EGC is still considered an initial phase of tumor progression with good prognosis. The introduction of modern endoscopic devices has allowed a precise diagnosis of early lesions, which can lead to improved definitions of tumors that can be radically treated with endoscopic mucosal resection or endoscopic submucosal dissection (ESD). Given the widespread use of these techniques, the Japanese Gastric Cancer Association (JGCA) identified in 2011 the standard criteria that should exclude the presence of lymph node metastases. At that time, EGCs with nodal involvement should have been asserted as no longer fitting the definition of an early tumor. Some authors have also demonstrated that the morphological growth pattern of a tumor, according to Kodama’s classification, is one of the most important prognostic factors, thereby suggesting the need to report it in histopathological drafts. Notwithstanding the acquired knowledge regarding the clinical behavior of EGC, Murakami’s definition is still being used. This definition needs to be upgraded according to the modern staging of the disease so that the appropriate treatment would be selected. PMID:26779372

  6. Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival.

    PubMed

    Makanji, Yogeshwar; Tagler, David; Pahnke, Jennifer; Shea, Lonnie D; Woodruff, Teresa K

    2014-04-15

    Oxygen tension is critical for follicle growth and metabolism, especially for early-stage follicles, where vascularity is limited. Its role and underlying mechanism in the in vitro activation and maturation of immature to ovulatory follicles is largely unknown. In this study, early secondary (110 μm) murine follicles were isolated and encapsulated in alginate hydrogels to replicate the in vivo environment of the growing/maturing follicle. Encapsulated follicles were cultured for 8 days at either 2.5 or 20% O2. Survival (2.6-fold) and growth (1.2-fold) were significantly higher for follicles cultured at 2.5% compared with 20% O2. Using a mouse hypoxia-signaling pathway qRT-PCR array and GeneGo Metacore analysis, we found that direct target genes of the hypoxia-activated HIF1-complex were significantly upregulated in follicles cultured for 8 days at 2.5% compared with 20% O2, including the carbohydrate transport and metabolism genes Slc2a3, Vegfa, Slc2a1, Edn1, Pgk1, Ldha, and Hmox1. Other upregulated genes included carbohydrate transporters (Slc2a1, Slc2a3, and Slc16a3) and enzymes essential for glycolysis (Pgk1, Hmox1, Hk2, Gpi1, Pfkl, Pfkp, Aldoa, Gapdh, Pgam1, Eno1, Pkm2, and Ldha). For follicles cultured at 2.5% O2, a 7.2-fold upregulation of Vegfa correlated to an 18-fold increase in VEGFA levels, and a 3.2-fold upregulation of Ldha correlated to a 4.8-fold increase in lactate levels. Both VEGFA and lactate levels were significantly higher in follicles cultured at 2.5% compared with 20% O2. Therefore, enhanced hypoxia-mediated glycolysis is essential for growth and survival of early secondary follicles and provides vital insights into improving in vitro culture conditions.

  7. 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. PMID:26760958

  8. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease.

    PubMed

    Mota, Sandra I; Costa, Rui O; Ferreira, Ildete L; Santana, Isabel; Caldeira, Gladys L; Padovano, Carmela; Fonseca, Ana C; Baldeiras, Inês; Cunha, Catarina; Letra, Liliana; Oliveira, Catarina R; Pereira, Cláudia M F; Rego, Ana Cristina

    2015-07-01

    Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative stress involving changes in Nrf2 and ER stress may constitute early events in AD pathogenesis by using human peripheral blood cells and an AD transgenic mouse model at different disease stages. Increased oxidative stress and increased phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood mononuclear cells (PBMCs) isolated from individuals with mild cognitive impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients. Evidence of early oxidative stress defense mechanisms in AD was substantiated by increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate oxidative stress and early Nrf2 activation in AD human and mouse models, which fails to regulate some of its targets, leading to repressed expression of antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Cumulative Effects of Nutrient Enrichment and Elevated Temperature Compromise the Early Life History Stages of the Coral Acropora tenuis.

    PubMed

    Humanes, Adriana; 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

  14. The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

    PubMed Central

    Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Muscarella, Aaron M.; Tian, Lin; Zhao, Hong; Zhao, Zhen; Du, Shiyu; Tao, Jianning; Lee, Brendan; Westbrook, Thomas F.; Wong, Stephen T. C.; Jin, Xin; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H.-F.

    2014-01-01

    Summary Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We further elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human datasets analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases. Significance In advanced stages, breast cancer bone metastases are driven by paracrine crosstalk among cancer cells, osteoblasts, and osteoclasts, which constitute a vicious osteolytic cycle. Current therapies targeting this process limit tumor progression, but do not improve patient survival. On the other hand, bone micrometastases may remain indolent for years before activating the vicious cycle, providing a therapeutic opportunity to prevent macrometastases. Here, we show that bone colonization is initiated in a microenvironment niche exhibiting active osteogenesis. Cancer and osteogenic cells form heterotypic adherens junctions, which enhance mTOR activity and drive early-stage bone colonization prior to osteolysis. These results reveal a strong connection between osteogenesis and micrometastasis and suggest potential therapeutic targets to prevent bone macrometastases. PMID:25600338

  15. Evidence from neglect dyslexia for morphological decomposition at the early stages of orthographic-visual analysis.

    PubMed

    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

  16. Molecular Simulation Study of the Early Stages of Formation of Bioinspired Mesoporous Silica Materials.

    PubMed

    Centi, Alessia; Jorge, Miguel

    2016-07-19

    The use of bioinspired templates, such as polyamines and polypeptides, could lead to significant improvements in the synthesis conditions under which mesoporous materials are traditionally produced, removing the need for strong pH as well as high temperature or pressure. In this work, we perform atomistic molecular dynamics simulations of 1,12-diaminododecane surfactants, in water and in the presence of silica monomers, to investigate the early stages of synthesis of one of the first examples of bioinspired silica materials. Different surfactant concentrations and pH were considered, clarifying the influence of the charge state of the molecules on the self-assembly process. We show that the amphiphilic amines form stable lamellar structures at equilibrium in the range from intermediate to high pH values. In a later stage, when silica species are added to the system, our results reveal that, in the same range of pH, silicates strongly adsorb around these aggregates at the interface with water. This causes a considerable modification of the curvature of the layer, which suggests a tendency for the system to evolve from a lamellar phase to the formation of vesicle structures. Furthermore, we show that silica monomers are able to penetrate the layer spontaneously when defects are created as a result of surfactants' head-to-head repulsion. These findings are in agreement with experimental observations and support the pillaring mechanism postulated for this class of materials. However, our simulations indicate that the aggregation process is driven by charge matching between surfactant heads and silica monomers rather than by hydrogen bond interactions between neutral species, as had been previously hypothesized. PMID:27340948

  17. Early clinical characteristics according to developmental stage in children with definite moyamoya disease.

    PubMed

    Kim, Young Ok; Joo, Sung-Pil; Seo, Bo-Ra; Rho, Young Il; Yoon, Woong; Woo, Young Jong

    2013-06-01

    The objective is to clarify the early clinical characteristics in childhood moyamoya disease (MD). Epidemiologic characteristics, symptoms and diagnostic rates were assessed in 64 children (0-18 years) with definite MD according to developmental stage: infancy (5; 0-1 years); toddlerhood/preschool age (22; 2-5 years); school age (29; 6-10 years); and adolescence (8; 11-18 years). The median ages at onset was 6.25 years and the female to male ratio was 1.9 (~2.5 in toddlerhood/preschool age and in adolescence, P=0.71). Previous headache was observed in 23% (14/64): frequently in school age (38%, P=0.02) and within 6 months before main symptoms (6/11). As an initial symptom, weakness was observed in 78% (50/64) mainly as transient ischemic attack (TIA, 61%) in limbs (90%) and unilaterally (82%). TIA was less frequent in infancy (40%, P=0.04). Seizure was observed in 27% (17/64): frequently in infancy (100%, P<0.01), as the focal type (71%), and in the right extremity (3:1). Isolated seizures without other symptoms was frequent in children ~5 years (P<0.01). Severe headache associated with MD was observed in 14% (9/64). Provoking events were positive in 42% (27/64): in school age, frequently during eating (28%); and in toddlerhood/preschool age, during crying (27%). The diagnostic rates at 3 and 12 months from symptom-onset were 39% (80% during infancy vs. 28% in school age, P=0.14) and 67%, respectively. Symptomatic progression at diagnosis was observed in 38% (24/64). Initial clinical characteristics in childhood definite MD differed according to developmental stage and from at diagnosis.

  18. 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.

  19. 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

  20. Hypofractionation with no boost after breast conservation in early-stage breast cancer patients.

    PubMed

    Arcadipane, Francesca; Franco, Pierfrancesco; De Colle, Chiara; Rondi, Nadia; Di Muzio, Jacopo; Pelle, Emanuela; Martini, Stefania; Ala, Ada; Airoldi, Mario; Donadio, Michela; De Sanctis, Corrado; Castellano, Isabella; Ragona, Riccardo; Ricardi, Umberto

    2016-10-01

    The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46 Gy/20 fractions or 40.05 Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57 months (range 6-124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6 %, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2 % of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95 %) had good-excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity. PMID:27573380

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. The temporal characteristics of the early and late stages of the L- and M-cone pathways that signal color

    PubMed Central

    Petrova, Daniela; Henning, G. Bruce; Stockman, Andrew

    2013-01-01

    Flickering long-wavelength light appears more yellow than steady light of the same average intensity. The hue change is consistent with distortion of the visual signal at some nonlinear site (or sites) that produces temporal components not present in the original stimulus (known as distortion products). We extracted the temporal attenuation characteristics of the early (prenonlinearity) and late (post-nonlinearity) filter stages in the L- and M-cone chromatic pathway by varying the input stimulus to manipulate the distortion products and the measuring of the observers' sensitivity to them. The early, linear, filter stage acts like a band-pass filter peaking at 10–15 Hz with substantial sensitivity losses at both lower and higher frequencies. Its characteristics are consistent with nonlinearity being early in the visual pathway but following surround inhibition. The late stage, in contrast, acts like a low-pass filter with a cutoff frequency around 3 Hz. The response of the early stage speeds up with radiance, but the late stage does not. A plausible site for the nonlinearity, which modelling suggests may be smoothly compressive but with a hard limit at high input levels, is after surround inhibition from the horizontal cells. PMID:23457358

  8. Different collagen types show distinct rates of increase from early to late stages of hepatitis C-related liver fibrosis.

    PubMed

    Chen, Wei; Rock, Jonathan B; Yearsley, Martha M; Ferrell, Linda D; Frankel, Wendy L

    2014-01-01

    During progression from normal liver to cirrhosis, total collagen increases nearly 10-fold with an abnormal increase in fibril-forming collagen and other extracellular matrix molecules. However, little is known regarding the changes each collagen type undergoes during fibrogenesis. We assessed the different collagen types by immunohistochemistry at various stages of hepatitis C-related liver fibrosis in core biopsies and compared changes in each with trichrome stain to better understand fibrogenesis. The possible utility in staging fibrosis was investigated. We found collagens III, IV, V, VI, vitronectin, and trichrome all showed statistically significant increases from early to late stages of fibrosis, but with temporal and quantitative differences. During the transition from early to late fibrosis, trichrome (stains primarily collagen I) and collagen IV showed the steepest increase and appear to be the most useful discriminators between early and late stages of fibrosis. Collagens V and VI have strong reactivity even in stage 1, which may be helpful in identifying early fibrosis when trichrome is weak or negative. Collagen III and vitronectin showed the most gradual increase. Interestingly, collagen V also showed increased staining in areas around inflammation/edema, which may overestimate established fibrosis as compared with trichrome.

  9. Transcriptome Analysis of the SL221 Cells at the Early Stage during Spodoptera litura Nucleopolyhedrovirus Infection

    PubMed Central

    Yu, Qian; Xiong, Youhua; Liu, Jianliang; Wen, Dongling; Wu, Xiaohui; Yin, Hanqi

    2016-01-01

    Spodoptera litura (S. litura) is one of the most destructive agricultural pests worldwide. There is urgent need for a nuclear polyhedrosis virus that is specific to S. litura. To date, there have been no reports regarding the responses of S. litura cells to early Spodoptera litura nucleopolyhedrovirus (SpltNPV) infection due to the lack of a reference genome and transcriptome for S. litura. In this study, a cell transcriptome from the host S. litura was assembled and used for Illumina strand-specific RNA sequencing (RNA-seq) to generate 99180 unigenes, representing the 18 hour infection cycle. More than 2000 S. litura genes were significant differentially regulated throughout the infection. The levels of viral mRNAs began to increase dramatically at 6 hpi, and this increase continued throughout the remainder of the infection. We focused on the expression of genes related to stress responses, apoptosis, metabolic enzymes and host cell innate immune system. A small subset of genes related to host stress response, especially for 62 ones being able to annotated as enzyme, ligand and receptor genes, were observed to be specifically differentially expressed at 6 hpi. At 18 hpi, 104 unigenes were continuously significantly changing from 0 hpi to 18 hpi, considered to be viral multiplication related genes, including 3 annotated SL221 unigenes and 81 viral genes, such as tetraspanin and iap gene. This information and further studies on the regulation of host gene expression by baculovirus infection at early stage will provide the tools needed to enhance the utility of this virus as an effective insecticide. PMID:26840182

  10. Contextual Valence and Sociality Jointly Influence the Early and Later Stages of Neutral Face Processing

    PubMed Central

    Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Yang, Dong

    2016-01-01

    Recent studies have demonstrated that face perception is influenced by emotional contextual information. However, because facial expressions are routinely decoded and understood during social communication, sociality should also be considered—that is, it seems necessary to explore whether emotional contextual effects are influenced by the sociality of contextual information. Furthermore, although one behavioral study has explored the effects of context on selective attention to faces, the exact underlying mechanisms remain unknown. Therefore, the current study investigated how valence and sociality of contextual information influenced the early and later stages of neutral face processing. We first employed an established affective learning procedure, wherein neutral faces were paired with verbal information that differed in valence (negative, neutral) and sociality (social, non-social), to manipulate contextual information. Then, to explore the effects of context on face perception, participants performed a face perception task, while the N170, early posterior negativity (EPN), and late positive potential (LPP) components were measured. Finally, to explore the effects of context on selective attention, participants performed a dot probe task while the N2pc was recorded. The results showed that, in the face perception task, faces paired with negative social information elicited greater EPN and LPP than did faces paired with neutral social information; no differences existed between faces paired with negative and neutral non-social information. In the dot probe task, faces paired with negative social information elicited a more negative N2pc amplitude (indicating attentional bias) than did faces paired with neutral social information; the N2pc did not differ between faces paired with negative and neutral non-social information. Together, these results suggest that contextual information influenced both face perception and selective attention, and these context

  11. Contextual Valence and Sociality Jointly Influence the Early and Later Stages of Neutral Face Processing

    PubMed Central

    Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Yang, Dong

    2016-01-01

    Recent studies have demonstrated that face perception is influenced by emotional contextual information. However, because facial expressions are routinely decoded and understood during social communication, sociality should also be considered—that is, it seems necessary to explore whether emotional contextual effects are influenced by the sociality of contextual information. Furthermore, although one behavioral study has explored the effects of context on selective attention to faces, the exact underlying mechanisms remain unknown. Therefore, the current study investigated how valence and sociality of contextual information influenced the early and later stages of neutral face processing. We first employed an established affective learning procedure, wherein neutral faces were paired with verbal information that differed in valence (negative, neutral) and sociality (social, non-social), to manipulate contextual information. Then, to explore the effects of context on face perception, participants performed a face perception task, while the N170, early posterior negativity (EPN), and late positive potential (LPP) components were measured. Finally, to explore the effects of context on selective attention, participants performed a dot probe task while the N2pc was recorded. The results showed that, in the face perception task, faces paired with negative social information elicited greater EPN and LPP than did faces paired with neutral social information; no differences existed between faces paired with negative and neutral non-social information. In the dot probe task, faces paired with negative social information elicited a more negative N2pc amplitude (indicating attentional bias) than did faces paired with neutral social information; the N2pc did not differ between faces paired with negative and neutral non-social information. Together, these results suggest that contextual information influenced both face perception and selective attention, and these context

  12. Contextual Valence and Sociality Jointly Influence the Early and Later Stages of Neutral Face Processing.

    PubMed

    Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Yang, Dong

    2016-01-01

    Recent studies have demonstrated that face perception is influenced by emotional contextual information. However, because facial expressions are routinely decoded and understood during social communication, sociality should also be considered-that is, it seems necessary to explore whether emotional contextual effects are influenced by the sociality of contextual information. Furthermore, although one behavioral study has explored the effects of context on selective attention to faces, the exact underlying mechanisms remain unknown. Therefore, the current study investigated how valence and sociality of contextual information influenced the early and later stages of neutral face processing. We first employed an established affective learning procedure, wherein neutral faces were paired with verbal information that differed in valence (negative, neutral) and sociality (social, non-social), to manipulate contextual information. Then, to explore the effects of context on face perception, participants performed a face perception task, while the N170, early posterior negativity (EPN), and late positive potential (LPP) components were measured. Finally, to explore the effects of context on selective attention, participants performed a dot probe task while the N2pc was recorded. The results showed that, in the face perception task, faces paired with negative social information elicited greater EPN and LPP than did faces paired with neutral social information; no differences existed between faces paired with negative and neutral non-social information. In the dot probe task, faces paired with negative social information elicited a more negative N2pc amplitude (indicating attentional bias) than did faces paired with neutral social information; the N2pc did not differ between faces paired with negative and neutral non-social information. Together, these results suggest that contextual information influenced both face perception and selective attention, and these context

  13. S-nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

    PubMed Central

    Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B.; Ravindra, Kodihalli C.; Wishnok, John S.; Tsai, Li-Huei; Tannenbaum, Steven R.

    2016-01-01

    Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein’s function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile the brain of the CK-p25–inducible mouse model of Alzheimer’s disease-like neurodegeneration. The approach—SNOTRAP (SNO trapping by triaryl phosphine)—is a direct tagging strategy that uses phosphine-based chemical probes, allowing enrichment of SNO-peptides and their identification by liquid chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. The SNO-proteome during early neurodegeneration identified increased S-nitrosation of proteins important for synapse function, metabolism, and Alzheimer’s disease pathology. In the latter case, proteins related to amyloid precursor protein processing and secretion are S-nitrosated, correlating with increased amyloid formation. Sequence analysis of SNO-cysteine sites identified potential linear motifs that are altered under pathological conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation of the SNO-proteome, providing functional insights of endogenous SNO proteins in the brain and its dysregulation during neurodegeneration. PMID:27035958

  14. Abnormal visual experience during development alters the early stages of visual-tactile integration.

    PubMed

    Niechwiej-Szwedo, Ewa; Chin, Jessica; Wolfe, Paul J; Popovich, Christina; Staines, W Richard

    2016-05-01

    Visual experience during the critical periods in early postnatal life is necessary for the normal development of the visual system. Disruption of visual input during this period results in amblyopia, which is associated with reduced activation of the striate and extrastriate cortices. It is well known that visual input converges with other sensory signals and exerts a significant influence on cortical processing in multiple association areas. Recent work in healthy adults has also shown that task-relevant visual input can modulate neural excitability at very early stages of information processing in the primary somatosensory cortex. Here we used electroencephalography to investigate visual-tactile interactions in adults with abnormal binocular vision due to amblyopia and strabismus. Results showed three main findings. First, in comparison to a visually normal control group, participants with abnormal vision had a significantly lower amplitude of the P50 somatosensory event related potential (ERP) when visual and tactile stimuli were presented concurrently. Second, the amplitude of the P100 somatosensory ERP was significantly greater in participants with abnormal vision. These results indicate that task relevant visual input does not significantly influence the excitability of the primary somatosensory cortex, instead, the excitability of the secondary somatosensory cortex is increased. Third, participants with abnormal vision had a higher amplitude of the P1 visual ERP when a tactile stimulus was presented concurrently. Importantly, these results were not modulated by viewing condition, which indicates that the impact of amblyopia on crossmodal interactions is not simply related to the reduced visual acuity as it was evident when viewing with the unaffected eye and binocularly. These results indicate that the consequences of abnormal visual experience on neurophysiological processing extend beyond the primary and secondary visual areas to other modality

  15. S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration.

    PubMed

    Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B; Ravindra, Kodihalli C; Wishnok, John S; Tsai, Li-Huei; Tannenbaum, Steven R

    2016-04-12

    Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein's function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile the brain of the CK-p25-inducible mouse model of Alzheimer's disease-like neurodegeneration. The approach-SNOTRAP (SNO trapping by triaryl phosphine)-is a direct tagging strategy that uses phosphine-based chemical probes, allowing enrichment of SNO-peptides and their identification by liquid chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. The SNO-proteome during early neurodegeneration identified increased S-nitrosation of proteins important for synapse function, metabolism, and Alzheimer's disease pathology. In the latter case, proteins related to amyloid precursor protein processing and secretion are S-nitrosated, correlating with increased amyloid formation. Sequence analysis of SNO-cysteine sites identified potential linear motifs that are altered under pathological conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation of the SNO-proteome, providing functional insights of endogenous SNO proteins in the brain and its dysregulation during neurodegeneration.

  16. 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.

  17. Dynamics of early stage nano-oxidation by in situ UHV-TEM

    NASA Astrophysics Data System (ADS)

    Yang, Judith

    2011-03-01

    Environmental stability is one of the most important properties for materials exposed to air. As dimensions of engineered systems approach nanoscale, fundamental understanding of reactions with oxygen at this length scale is critical for environmental stability as well as for processing oxide nanostructures, where surface reactions are commonly utilized. The nanoscale stages of oxidation from the nucleation of the metal oxide to the formation of the thermodynamically stable oxide represent a scientifically challenging and technologically important terra incognito. The kinetics of early stage oxidation of Cu, Cu-Au and Cu-Ni alloys were visualized using in situ ultra-high vacuum transmission electron microscopy (UHV-TEM), where the initial oxidation stages can be observed in real-time under well-controlled surface conditions. We examined the dynamic responses of thin films to variations in thermodynamic variables such as temperature, oxygen pressure, strain, and crystallographic orientation. The kinetics of the nucleation and growth of three-dimensional oxide islands demonstrate that oxygen surface diffusion is the primary mechanism for oxide growth during initial oxidation in dry oxygen, and thus bears a striking resemblance to heteroepitaxy. Compared with the behavior of Cu films, the oxidation of Cu-Au alloys revealed more complexity. For example, the oxidation of (100)-oriented Cu-Au alloys with low Au content at ~ 600 C results in the formation of Cu2O oxide islands with a dendritic morphology and a non-uniform lateral distribution of Au around the islands. For Cu-Ni oxidation, the addition of Ni causes the formation Cu2O and/or NiO where the oxide type(s) and the relative orientation with the film depend on the Ni concentration, oxygen partial pressure and temperature. Evolution of the shape and size of the oxide islands can be quantitatively analyzed and provide fundamental insights into the complex kinetics and energetics of oxidation. Models based on

  18. Sensitivity of the early life stages of macroalgae from the Northern Hemisphere to ultraviolet radiation.

    PubMed

    Roleda, Michael Y; Wiencke, Christian; Hanelt, Dieter; Bischof, Kai

    2007-01-01

    possess several mechanisms to minimize UVR damage and, hence, are less sensitive but at the expense of growth. The species-specific susceptibility of the early life stages of macroalgae to UVR plays an important role for the determination of zonation patterns and probably also for shaping up community structure. PMID:17645656

  19. 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.

  20. 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. PMID:24698029

  1. 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. PMID:25646107

  2. 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...

  3. 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

  4. Amino and fatty acid dynamics of octopus (Octopus vulgaris) early life stages under ocean warming.

    PubMed

    Lopes, Vanessa M; Faleiro, Filipa; Baptista, Miguel; Pimentel, Marta S; Paula, José R; Couto, Ana; Bandarra, Narcisa; Anacleto, Patrícia; Marques, António; Rosa, Rui

    2016-01-01

    The oceans are becoming warmer, and the higher temperatures are expected to have a major impact on marine life at different levels of biological organization, especially at the most vulnerable early life stages. Thus, we hypothesize that the future warmer scenarios (here +3 °C) will affect the biochemical composition (amino acid - AA, and fatty acid-FA) of octopod (Octopus vulgaris) embryos and recently-hatched pelagic paralarvae. The main essential amino acids found in octopus embryos were arginine, leucine and lysine; while aspartic and glutamic acids, and taurine were the main non-essential amino acids. Palmitic, eicosapentaenoic and docosahexaenoic acids were the main FAs found in octopus tissues. Relevant ontogenetic changes were observed, namely a steep decrease in the content of many AAs, and a selective retention of FAs, thus evidencing the protein-based metabolism of these cephalopods. Temperature per si did not elicit significant changes in the overall FA composition, but was responsible for a significant decrease in the content of several AAs, indicating increased embryonic consumption.

  5. 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

    2013-10-01

    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. PMID:23926158

  6. 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.

  7. EARLY-STAGE MASSIVE STAR FORMATION NEAR THE GALACTIC CENTER: Sgr C

    SciTech Connect

    Kendrew, S.; Johnston, K.; Beuther, H.; Ginsburg, A.; Bally, J.; Battersby, C.; Cyganowski, C. J.

    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 H{sub 2} and Brackett γ emission alongside a previously detected compact radio source. We calculate the cores' joint mass to be ∼10{sup 3} M {sub ☉}, with column densities of 1-2 × 10{sup 24} cm{sup –2}. We show the host molecular cloud to hold ∼10{sup 5} M {sub ☉} 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.

  8. Early stages of growth and crystal structure evolution of boron nitride thin films

    NASA Astrophysics Data System (ADS)

    Henry, Anne; Chubarov, Mikhail; Czigány, Zsolt; Garbrecht, Magnus; Högberg, Hans

    2016-05-01

    A study of the nucleation and crystal structure evolution at the early stages of the growth of sp2-BN thin films on 6H-SiC and α-Al2O3 substrates is presented. The growth is performed at low pressure and high temperature in a hot wall CVD reactor, using ammonia and triethylboron as precursors, and H2 as carrier gas. From high-resolution transmission electron microscopy and X-ray thin film diffraction measurements we observe that polytype pure rhombohedral BN (r-BN) is obtained on 6H-SiC substrates. On α-Al2O3 an AlN buffer obtained by nitridation is needed to promote the growth of hexagonal BN (h-BN) to a thickness of around 4 nm followed by a transition to r-BN growth. In addition, when r-BN is obtained, triangular features show up in plan-view scanning electron microscopy which are not seen on thin h-BN layers. The formation of BN after already one minute of growth is confirmed by X-ray photoelectron spectroscopy.

  9. Do Diacritical Marks Play a Role at the Early Stages of Word Recognition in Arabic?

    PubMed Central

    Perea, Manuel; Abu Mallouh, Reem; Mohammed, Ahmed; Khalifa, Batoul; Carreiras, Manuel

    2016-01-01

    A crucial question in the domain of visual word recognition is whether letter similarity plays a role in the early stages of visual word processing. Here we focused on Arabic because in this language there are various groups of letters that share the same basic shape and only differ in the number/location of diacritical points. We conducted a masked priming lexical decision experiment in which a target word was preceded by: (i) an identity prime; (ii) a prime in which the critical letter was replaced by a letter with the same shape that differed in the number of diacritics (e.g., ); or (iii) a prime in which the critical letter was replaced by a letter with different shape (e.g., ). Results showed a sizable advantage of the identity condition over the two substituted-letter priming conditions (i.e., diacritical information is rapidly processed). Thus, diacritical marks play an essential role in the “feature letter” level of models of visual word recognition in Arabic. PMID:27597838

  10. Lipid peroxidation may not be important in an early stage of alcohol-induced liver injury

    SciTech Connect

    Inomata, T.; Rao, G.A.; Tsukamoto, H.

    1986-03-01

    Role of lipid peroxidation (LP) in alcoholic liver injury (ALI) is still controversial. The authors have previously described a rat model which produced the sequential injury from alcoholic fatty liver to liver necrosis and fibrosis. In the present study, the authors have examined the degree of LP and GSH/GSSG ratio in the liver to investigate whether the LP can be identified in an early stage of progressive ALI. Six pairs of male Wistar rats were continuously infused intragastrically for 30 days with a high fat diet (25% total calories) plus either ethanol or isocaloric amount of dextrose. Following intoxication, the content of diene conjugates in mitochondrial and microsomal lipids as well as the liver GSH/GSSG ratio were determined by the diene difference spectrum and fluorometry, respectively. The UV absorption at 234nm by mitochondrial lipid from alcoholic rats (0.668 +/- 0.023 OD/mg) was significantly (p<0.05) lower than that of controls (0.977 +/- 0.102 OD/mg). The microsomal lipid, however, exhibited a similar absorbance in the two groups (0.986 +/- 0.086 vs 1.149 +/- 0.091 OD/mg0. Similarly, no difference in the ratio of GSH/GSSG was found (6.05 +/- 0.27 vs 5.35 +/- 0.44). These results do not support a concept that LP is an important pathogenetic factor for the progression of alcoholic fatty liver to liver necrosis.

  11. 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. PMID:20951746

  12. Differences in early and late stages of information processing between slow versus fast participants.

    PubMed

    Portella, Claudio; Machado, Sergio; Paes, Flávia; Cagy, Mauricio; Sack, Alexander T; Sandoval-Carrillo, Ada; Salas-Pacheco, Jose; Silva, Adriana Cardoso; Piedade, Roberto; Ribeiro, Pedro; Nardi, Antonio Egídio; Arias-Carrión, Oscar

    2014-01-01

    The human brain is a system consisting of various interconnected neural networks, with functional specialization coexisting with functional integration occurring both; temporally and spatially at many levels. The current study ranked and compared fast and slow participants in processing information by assessing latency and amplitude of early and late Event-Related Potential (ERP) components, including P200, N200, Premotor Potential (PMP) and P300. In addition, the Reaction Time (RT) of participants was compared and related to the respective ERP components. For this purpose, twenty right-handed and healthy individuals were subjected to a classical ERP "Oddball" paradigm. Principal Component Analysis (PCA) and Discriminant Function analyses (DFA) used PRE components and the Reaction Time (RT) to classify individuals. Our results indicate that latencies of P200 (O2 electrode), N200 (O2), PMP (C3) and P300 (Pz) components are significantly reduced in the group of fast responding participants. In addition, the P200 amplitude is significantly increased in the group of fast responding participants. Based on these findings, we suggest that the ERP is able to detect even minimal impairments, in the processing of somatosensory information and cognitive and motor stages. Hence, the study of ERP might also be capable of assessing sensorimotor dysfunctions in healthy old-aged people and in neuropsychiatric patients (suffering from dementia, Parkinson's disease, and other neurological disorders). PMID:25838842

  13. Influence of the surface morphology on the early stages of Cu oxidation

    NASA Astrophysics Data System (ADS)

    Luo, Langli; Kang, Yihong; Yang, Judith C.; Zhou, Guangwen

    2012-10-01

    The growth and morphological features of Cu films deposited on NaCl(1 0 0) by e-beam evaporation have been examined to evaluate the effect of various surface morphologies on the initial oxidation of Cu. It is shown that epitaxial Cu films with significantly reduced surface roughness can be achieved by first nucleating Cu seeds at 450 °C that favors epitaxial Cu grains which is followed by subsequent seed growth at 150 °C that favors smooth Cu film. The effect of the variations of the surface morphology of the resulting Cu films by the different growth conditions on the early stages oxidation of Cu films is examined by in situ transmission electron microscopy (TEM) and ex situ atomic force microscopy (AFM). It is shown that the changes in the surface morphologies of the Cu film result in distinct variations in the nucleation density and growth rates of oxide islands. Such correlation between the surface morphology and the initial oxidation behavior of the Cu films provides insights into understanding the microscopic processes of the transient oxidation of metals and for manipulating the initial oxide formation through surface treatments.

  14. The toxicity of titanium dioxide nanopowder to early life stages of the Japanese medaka (Oryzias latipes).

    PubMed

    Paterson, Gordon; Ataria, Jamie M; Hoque, M Ehsanul; Burns, Darcy C; Metcalfe, Chris D

    2011-02-01

    In this study, fertilized Japanese medaka (Oryzias latipes) embryos were exposed from fertilization to 5 d post-hatch using static non-renewal assays to aqueous suspensions of titanium dioxide nanoparticles (nTiO₂) ranging in nominal concentrations between 0 and 14 μg mL⁻¹. The average size of the nTiO₂ in the stock solution before addition to the test treatments was 87 nm (±14 nm). TiO₂ materials accumulated in a concentration dependent manner on the chorionic filaments of developing medaka embryos with evidence of pericardial edema occurring during embryo development. However, no significant (p > 0.05) increases in mortality relative to control treatments were observed for the nTiO₂ exposed embryos. A concentration dependent increase in cumulative percent hatch was observed at 11 d, indicating that expo