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Sample records for induces early emergence

  1. Prospective 2-Year Study of Emergency Department Patients With Early-Phase Primary Psychosis or Substance-Induced Psychosis

    Science.gov (United States)

    Drake, Robert E.; Caton, Carol L.M.; Xie, Haiyi; Hsu, Eustace; Gorroochurn, Prakash; Samet, Sharon; Hasin, Deborah S.

    2013-01-01

    Objective The authors examined treatment utilization and outcomes over 2 years among patients admitted to emergency departments with early-phase primary or substance-induced psychosis. The main hypothesis was that patients with substance-induced psychosis would have a more benign course of illness than those with primary psychosis. Method Using a prospective naturalistic cohort study design, the authors compared 217 patients with early-phase primary psychosis plus substance use and 134 patients with early-phase substance-induced psychosis who presented to psychiatric emergency departments at hospitals in Upper Manhattan. Assessments at baseline and at 6, 12, 18, and 24 months included psychiatric diagnoses, service use, and institutional outcomes using the Psychiatric Research Interview for Substance and Mental Disorders; psychiatric symptoms using the Positive and Negative Syndrome Scale; social, vocational, and family functioning using the World Health Organization Psychiatric Disability Assessment Schedule; and life satisfaction using the Quality of Life Interview. Longitudinal analyses were conducted using generalized estimating equations. Results Participants with primary psychosis were more likely to receive antipsychotic and mood-stabilizing medications, undergo hospitalizations, and have out-patient psychiatric visits; those with substance-induced psychosis were more likely to receive addiction treatments. Only a minority of each group received minimally adequate treatments. Both groups improved significantly over time on substance dependence, psychotic symptoms, homelessness, and psychosocial outcomes, and few group-by-time interactions emerged. Conclusions Patients presenting to Upper Manhattan emergency departments with either early-phase primary psychosis or substance-induced psychosis improved steadily over 2 years despite minimal use of mental health and substance abuse services. PMID:21454918

  2. Early identification systems for emerging foodborne hazards

    NARCIS (Netherlands)

    Marvin, H.J.P.; Kleter, G.A.; Pradini, A.; Dekkers, S.; Bolton, D.J.

    2009-01-01

    This paper provides a non-exhausting overview of early warning systems for emerging foodborne hazards that are operating in the various places in the world. Special attention is given to endpoint-focussed early warning systems (i.e. ECDC, ISIS and GPHIN) and hazard-focussed early warning systems

  3. Early emergency prognosis and response centers

    International Nuclear Information System (INIS)

    An emergency early warning system for the fourteen nuclear generating units in the country has been developed at the Nuclear Research Institute of the Ukrainian Academy of Sciences. All units are connected to the host computer in the emergency center of the State Nuclear Power Authority in Kiew and interconnected with each other. The early warning system is to make another reactor accident of the magnitude of Chernobyl impossible. Installation of the hardware is to begin at the South Ukraine 3 nuclear generating unit in 1997; the costs of the pilot project are estimated at U.S. Dollar 40 million. After subsequent feasibility studies, the software and the hardware may be modified; the early warning system could be in operation countrywide by 1999. (orig.) [de

  4. Methylphenidate Actively Induces Emergence from General Anesthesia

    Science.gov (United States)

    Solt, Ken; Cotten, Joseph F.; Cimenser, Aylin; Wong, Kin F.K.; Chemali, Jessica J.; Brown, Emery N.

    2011-01-01

    Background Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study we tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane anesthesia. Methods Using adult rats we tested the effect of methylphenidate IV on time to emergence from isoflurane anesthesia. We then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate–induced restoration of righting during continuous isoflurane anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Droperidol IV was administered to test for inhibition of methylphenidate's actions. Results Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without compared to with methylphenidate was 200 [155, 331] s (median, [95% confidence interval]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta to theta, and induced an increase in minute ventilation. Administration of droperidol (0.5 mg/kg IV) prior to methylphenidate (5 mg/kg IV) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Conclusions Methylphenidate actively induces emergence from isoflurane anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. Our findings suggest that methylphenidate may be clinically

  5. [(Early) Palliative Care in Emergency Medicine].

    Science.gov (United States)

    Spickermann, Maximilian; Lenz, Philipp

    2018-04-01

    At the end of life patients with a life-limiting disease are often admitted to emergency departments (ED). Mostly, in the setting of an ED there may not be enough time to meet the needs for palliative care (PC) of these patients. Therefore, integration of PC into the ED offers a solution to improve their treatment. In the outpatient setting a cooperation between prehospital emergency services, the patient's general practitioner and specialized outpatient PC teams may allow the patient to die at home - this is what most patients prefer at the end of life. Furthermore, due to the earlier integration of PC after admission the hospital stay is shortened. Also the number of PC consultations may increase. Additionally, a screening of PC hneeds among all patients visiting the ED may be beneficial: to avoid not meeting existing PC needs and to standardize the need of PC consultation. An example for such a screening tool is the "Palliative Care and Rapid Emergency Screening" (P-CaRES). © Georg Thieme Verlag KG Stuttgart · New York.

  6. Privacy Attitudes among Early Adopters of Emerging Health Technologies.

    Science.gov (United States)

    Cheung, Cynthia; Bietz, Matthew J; Patrick, Kevin; Bloss, Cinnamon S

    2016-01-01

    Advances in health technology such as genome sequencing and wearable sensors now allow for the collection of highly granular personal health data from individuals. It is unclear how people think about privacy in the context of these emerging health technologies. An open question is whether early adopters of these advances conceptualize privacy in different ways than non-early adopters. This study sought to understand privacy attitudes of early adopters of emerging health technologies. Transcripts from in-depth, semi-structured interviews with early adopters of genome sequencing and health devices and apps were analyzed with a focus on participant attitudes and perceptions of privacy. Themes were extracted using inductive content analysis. Although interviewees were willing to share personal data to support scientific advancements, they still expressed concerns, as well as uncertainty about who has access to their data, and for what purpose. In short, they were not dismissive of privacy risks. Key privacy-related findings are organized into four themes as follows: first, personal data privacy; second, control over personal information; third, concerns about discrimination; and fourth, contributing personal data to science. Early adopters of emerging health technologies appear to have more complex and nuanced conceptions of privacy than might be expected based on their adoption of personal health technologies and participation in open science. Early adopters also voiced uncertainty about the privacy implications of their decisions to use new technologies and share their data for research. Though not representative of the general public, studies of early adopters can provide important insights into evolving attitudes toward privacy in the context of emerging health technologies and personal health data research.

  7. Risk management: application of early warning systems to emergency plans

    Science.gov (United States)

    Garcia, C.; Sterlacchini, S.; Pasuto, A.; de Amicis, M.

    2009-04-01

    Warning System and emergency plans are two fundamental elements of risk management and governance, but unfortunately, most of the times, they are developed independently one from the other, as sequential steps not necessary linked. The main goal of this research is to develop a methodology for applying Early Warning Systems - Community Based to the emergency plan using the results of social surveys and quantitative risk assessment, taking into account the administrative structure and the planning system of the study area, as well as the legislative obligations of each entity involved in the risk governance and emergency management. Using a integrative scientific and social approach to natural hazards the research aim to contribute to fill the gap between scientists, policy makers, stakeholders and community. Initially applied in Comunità Montana Valtellina di Tirano, Italy, the methodology involves the application of two comprehensive surveys. The first is addressed to stakeholders (including policy makers, emergency managers, emergency volunteers, consultants and scientists) in order to determine their needs, points of view, concerns and constraints. The second survey is addressed specifically to local community to assess risk perception, awareness, needs, capacity and level of trust towards stakeholders, besides asking for their willingness to participate in future risk communication activities. The Early Warning System developed includes all the stages of the early warning process (hazard evaluation and forecasting; warning and dissemination and public response) and would be based on a multidisciplinary partnership that takes into account the different actors involved in the risk management in order to accomplish a more reliable and credible result, including an emergency plan specifically designed for each study area. After evaluating the results of the surveys, information and education campaigns will be developed with the objective of reducing vulnerability

  8. The Clinical Course of a Drug-induced Acute Dystonic Reaction in the Emergency Room

    Directory of Open Access Journals (Sweden)

    Massimo Marano

    2016-12-01

    Full Text Available Background: Acute dystonic reactions following the administration of safe, reliable drugs can occur and must be promptly recognized and treated in the emergency room.Phenomenology Shown: The entire clinical course of an acute dystonic reaction due to metoclopramide, from early motor signs to full-blown clinical symptoms and resolution.Educational Value: Providing elements for early recognition of a drug-induced movement disorder phenomenology.   

  9. Thermal and quantum induced early superstring cosmology

    CERN Document Server

    Bourliot, F; Kounnas, C; Partouche, H

    2009-01-01

    In this work, we review the results of Refs [1]-[5] dedicated to the description of the early Universe cosmology induced by quantum and thermal effects in superstring theories. The present evolution of the Universe is described very accurately by the standard Lambda-CDM scenario, while very little is known about the early cosmological eras. String theory provides a consistent microscopic theory to account for such missing epochs. In our framework, the Universe is a torus filled with a gas of superstrings. We first show how to describe the thermodynamical properties of this system, namely energy density and pressure, by introducing temperature and supersymmetry breaking effects at a fundamental level by appropriate boundary conditions. We focus on the intermediate period of the history: After the very early "Hagedorn era" and before the late electroweak phase transition. We determine the back-reaction of the gas of strings on the initially static space-time, which then yields the induced cosmology. The consist...

  10. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Johansson, Pär I

    2012-01-01

    There is emerging evidence that early trauma-induced coagulopathy (TIC) is mechanistically linked to disruption of the vascular endothelium and its glycocalyx, assessed by thrombomodulin and syndecan 1, respectively. This study evaluated if degradation of the endothelial glycocalyx and ensuing...... release of its heparin-like substances induce autoheparinization and thereby contributes to TIC....

  11. Early detection of abnormal patient arrivals at hospital emergency department

    KAUST Repository

    Harrou, Fouzi

    2015-10-21

    Overcrowding is one of the most crucial issues confronting emergency departments (EDs) throughout the world. Efficient management of patient flows for ED services has become an urgent issue for most hospital administrations. Handling and detection of abnormal situations is a key challenge in EDs. Thus, the early detection of abnormal patient arrivals at EDs plays an important role from the point of view of improving management of the inspected EDs. It allows the EDs mangers to prepare for high levels of care activities, to optimize the internal resources and to predict enough hospitalization capacity in downstream care services. This study reports the development of statistical method for enhancing detection of abnormal daily patient arrivals at the ED, which able to provide early alert mechanisms in the event of abnormal situations. The autoregressive moving average (ARMA)-based exponentially weighted moving average (EWMA) anomaly detection scheme proposed was successfully applied to the practical data collected from the database of the pediatric emergency department (PED) at Lille regional hospital center, France.

  12. Early emergence of Yersinia pestis as a severe respiratory pathogen.

    Science.gov (United States)

    Zimbler, Daniel L; Schroeder, Jay A; Eddy, Justin L; Lathem, Wyndham W

    2015-06-30

    Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals.

  13. Emergency department management of early sepsis: a national survey of emergency medicine and intensive care consultants.

    Science.gov (United States)

    Jiwaji, Zoeb; Brady, Shirin; McIntyre, Lauralyn A; Gray, Alasdair; Walsh, Timothy S

    2014-12-01

    Early goal-directed therapy (EGDT) is recommended for sepsis management in current guidelines, but the underpinning evidence is controversial. Clinician beliefs and the capacity to implement all recommended elements of EGDT in emergency departments (EDs) are uncertain. Our study aimed to explore self-reported management of early sepsis by Scottish emergency medicine (EM) and intensive care medicine (ICM) consultants, delineate important differences and determine the guideline recommendations rated most important and deliverable within the ED. A postal survey using a hypothetical patient with septic shock was sent to all EM and ICM consultants practising in Scotland. 67% (76/114) EM and 61% (96/157) ICM consultants responded. Normal saline was preferred by EM respondents ('always/often used': EM 86%, ICM 23%, pmanagement of sepsis exist between Scottish ICM and EM consultants. Transfusion practice is highly variable, suggesting clinical uncertainty. Lactate is considered more important than ScVO2 measurement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Emergence and early survival of early versus late seral species in Great Basin restoration in two different soil types

    Science.gov (United States)

    Shauna M. Uselman; Keirith A. Snyder; Elizabeth A. Leger; Sara E. Duke

    2015-01-01

    Comparing emergence and survival probabilities, early seral natives generally outperformed late seral natives when growing with exotics and had earlier emergence timing, although results differed among functional groups and soil types. In contrast, survival probabilities did not differ between the early and late seral mixes when growing without exotics. Within each...

  15. [Emergence of early childhood trauma in adult psychiatric symptomatology].

    Science.gov (United States)

    Bouras, G; Lazaratou, E

    2012-06-01

    DNA methylation and brain development. Supporting the family and break the silence that frequently covers the traumatic events and feelings, will give the opportunity for the elaboration of all these aspects which could capture and imprison the subject in a dramatic circle of psychopathology. Moreover, the effectiveness of early interventions and child psychotherapy is now a common ground, so we have to use all our clinical instruments (dialogue, symbolic play, drawing, storytelling) in order to help the child and have the best possible result. Finally, concerning clinical practice, the emergence of early childhood trauma in adult psychiatric symptomatology is so frequent that mental health experts should take it into serious account while developing an appropriate clinical treatment for such patients.

  16. An Early Warning System for Overcrowding in the Emergency Department

    Science.gov (United States)

    Hoot, Nathan; Aronsky, Dominik

    2006-01-01

    Overcrowding of emergency departments impedes health care access and quality nationwide. A real-time early warning system for overcrowding may allow administrators to alleviate the problem before reaching a crisis state. Two original probabilistic models – a logistic regression and a recurrent neural network – were created to predict overcrowding crises one hour in the future. The two original and two pre-existing models were validated at 8,496 observation points from January 1, 2006 to February 28, 2006. All models showed high discriminatory ability in terms of area under the receiver operating characteristic curve (logistic regression = .954; recurrent neural network = .957; EDWIN = .879; NEDOCS = .924). At comparable rates of false alarms, the logistic regression gave more advance notice of crises than other models (logistic regression = 62 min; recurrent neural network = 13 min; EDWIN = 0 min; NEDOCS = 0 min). These results demonstrate the feasibility of using models based on key operational variables to anticipate overcrowding crises in real time. PMID:17238359

  17. Early onset pregnancy induced hypertension/eclampsia in Benin ...

    African Journals Online (AJOL)

    induced hypertension /eclampsia in a Nigerian tertiary hospital, and compare maternofetal outcome in early and late onset disease. : A retrospective study of all cases of early onset pregnancy induced hypertension/eclampsia seen over a five-year period in a tertiary hospital. : Severity of disease, rates of induction of labour, ...

  18. The emergence of functional architecture during early brain development

    NARCIS (Netherlands)

    Keunen, Kristin; Counsell, Serena J.; Benders, Manon J.N.L.

    2017-01-01

    Early human brain development constitutes a sequence of intricate processes resulting in the ontogeny of functionally operative neural circuits. Developmental trajectories of early brain network formation are genetically programmed and can be modified by epigenetic and environmental influences. Such

  19. External validation of the Emergency Trauma Score for early prediction of mortality in trauma patients

    NARCIS (Netherlands)

    Joosse, Pieter; de Jong, Willem-Jan J.; Reitsma, Johannes B.; Wendt, Klaus W.; Schep, Niels W.; Goslings, J. Carel

    2014-01-01

    The Emergency Trauma Score has been developed for early estimation of mortality risk in adult trauma patients with an Injury Severity Score of 16 or higher. Emergency Trauma Score combines four early predictors available at the trauma resuscitation room: age, Glasgow Coma Scale, base excess, and

  20. External Validation of the Emergency Trauma Score for Early Prediction of Mortality in Trauma Patients

    NARCIS (Netherlands)

    Joosse, Pieter; de Jong, Willem-Jan J.; Wendt, Klaus W.; Schep, Niels W.; Goslings, J. Carel; Reitsma, J.

    Objectives: The Emergency Trauma Score has been developed for early estimation of mortality risk in adult trauma patients with an Injury Severity Score of 16 or higher. Emergency Trauma Score combines four early predictors available at the trauma resuscitation room: age, Glasgow Coma Scale, base

  1. Active Emergence from Propofol General Anesthesia is Induced by Methylphenidate

    Science.gov (United States)

    Chemali, Jessica J.; Van Dort, Christa J.; Brown, Emery N.; Solt, Ken

    2012-01-01

    BACKGROUND A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia. METHODS Using adult rats, the effect of methylphenidate on time to emergence after a single bolus of propofol was determined. The ability of methylphenidate to restore righting during a continuous target controlled infusion of propofol was also tested. In a separate group of rats, a target controlled infusion of propofol was established and spectral analysis was performed on electroencephalogram recordings taken before and after methylphenidate administration. RESULTS Methylphenidate decreased median time to emergence after a single dose of propofol from 735 seconds (95% CI: 598 to 897 seconds, n=6) to 448 seconds (95% CI: 371 to 495 seconds, n=6). The difference was statistically significant (p = 0.0051). During continuous propofol anesthesia with a median final target plasma concentration of 4.0 μg/ml (95%CI: 3.2 to 4.6, n=6), none of the rats exhibited purposeful movements after injection of normal saline. After methylphenidate, however, all 6 rats promptly exhibited arousal and had restoration of righting with a median time of 82 seconds (95% CI: 30 to 166 seconds). Spectral analysis of electroencephalogram data demonstrated a shift in peak power from delta (anesthesia in rats. Further study is warranted to test the hypothesis that methylphenidate induces emergence from propofol general anesthesia in humans. PMID:22446983

  2. Drug-induced angioedema: experience of Italian emergency departments.

    Science.gov (United States)

    Bertazzoni, G; Spina, M T; Scarpellini, M G; Buccelletti, F; De Simone, M; Gregori, M; Valeriano, V; Pugliese, F R; Ruggieri, M P; Magnanti, M; Susi, B; Minetola, L; Zulli, L; D'Ambrogio, F

    2014-06-01

    Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.

  3. Ethanol Induced Urine Acidification is Related with Early Acetaldehyde Concentration

    Directory of Open Access Journals (Sweden)

    Soon Kil Kwon

    2014-06-01

    Conclusion: In conclusion, urine acidification after ethanol ingestion is related with serum acetaldehyde concentration. Early elevation of acetaldhyde could induce urine acidification, but the urine pH was elevated after a few hours, that might make prolonged acidemia.

  4. Biochemical investigation of earliness in radiation induced early flowering mutantlines of jute Corchorus capsularis L

    International Nuclear Information System (INIS)

    Islam, M.S.; Ilias, M.; Biswas, A.K.; Naznin, S.

    1980-01-01

    With the help of radiation induced early and late flowering mutantlines of jute, studies have been made to determine the biochemical factors which could regulate the induction and expression of genes for the flowering processes in this plant. Comparative biochemical investigations were done with the parameters like : plant pigments (Chlorophyl a, b and carotenoides), auxin/antiauxin, and gibberellin/anti-gibberellin type of substances. Quantitative as well as qualitative differences of plant pigments were observed between the early and late flowering lines. Extracts of early flowering lines have been found to induce earliness in the late flowering mother variety of jute (D-154). Re-isolated growth inhibitors of early flowering lines have also been found to induce earliness in the late flowering mother variety (D-154). (author)

  5. The emergence of mound cemeteries in Early Dilmun:

    DEFF Research Database (Denmark)

    Laursen, Steffen

    2010-01-01

    . 2050-2000 BC, which has been identified within the greater Karzakkan Cemetery. It is argued that the emergence of the compact Dilmun cemeteries is a product of new, larger and more permanent rural settlements. Further; it is demonstrated that the earliest parts of the cemetery were associated...... the later Dilmun seals. Together with the introduction of a broad variety of imported vessels from Mesopotamia, SW Iran and the Indus, the evolution in local pottery is taken to reflect a fundamental restructuration of Dilmun's network of exchange at the time of the emerging cemeteries. The proto...

  6. Psychosocial Intimacy and Identity: From Early Adolescence to Emerging Adulthood

    Science.gov (United States)

    Montgomery, Marilyn J.

    2005-01-01

    Age and gender differences in patterns of behavior and experience, cognitive beliefs, affective involvement, and psychosocial functioning in romantic relationships were observed in 473 adolescents and emerging adults (ages 12-24). Older adolescents indicated more dating experiences, times in love, passion, identity, and intimacy. They also…

  7. Early Career Teachers' Emotion and Emerging Teacher Identities

    Science.gov (United States)

    Nichols, Sharon L.; Schutz, Paul A.; Rodgers, Kelly; Bilica, Kimberly

    2017-01-01

    The goal of our project was to develop an understanding of the connections among emotional episodes and emerging professional teacher identities of first year teachers. We interviewed eight first year mathematics and science teachers. We asked them to reflect on emotional episodes and talk about how those emotions informed their teaching…

  8. Management of drug-induced hyperbilirubinaemia in early pregnancy

    African Journals Online (AJOL)

    lymphocyte stimulation tests for piperidolate hydrochloride were negative, but in view of the patient's clinical course we concluded that her hyperbilirubinaemia was caused by drug-induced hepatotoxicity. Management of drug-induced hyperbilirubinaemia in early pregnancy. H Tsuyoshi, K Nishijima, J Takahashi, Y Yoshida.

  9. Radiation induced early maturing mutants in barley

    International Nuclear Information System (INIS)

    Kumar, R.; Chauhan, S.V.S.; Sharma, R.P.

    1978-01-01

    In M 2 generation, two early maturing plants were screened from a single spike progeny of a plant obtained from 20 kR of gamma-ray irradiation of a six-rowed barley (Hordeum vulgare L. var. Jyoti). Their true breeding nature was confirmed in M 3 generation. These mutants flower and mature 38 and 22 days earlier than those of control. (auth.)

  10. Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five.

    Science.gov (United States)

    Mulder, Hanna; Verhagen, Josje; Van der Ven, Sanne H G; Slot, Pauline L; Leseman, Paul P M

    2017-01-01

    Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about.

  11. Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five

    Directory of Open Access Journals (Sweden)

    Hanna Mulder

    2017-10-01

    Full Text Available Previous work has shown that individual differences in executive function (EF are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about.

  12. Estimating plant stem emerging points (PSEPs) of sugar of beets in early growth stages

    DEFF Research Database (Denmark)

    Midtiby, Henrik; Mosgaard Giselsson, Thomas; Jørgensen, Rasmus Nyholm

    2012-01-01

    Successful intra--row mechanical weed control of sugar beet 
(beta vulgaris) in early growth stages requires precise 
knowledge about location of crop plants.
A computer vision system for locating Plant Stem Emerging Point (PSEP) 
of sugar beet in early growth stages was developed and tested...

  13. Nurse-administered early warning score system can be used for emergency department triage

    DEFF Research Database (Denmark)

    Christensen, Dorthea; Jensen, Nanna Martin; Maaløe, Rikke

    2011-01-01

    Studies have shown that early warning score systems can identify in-patients at high risk of catastrophic deterioration and this may possibly be used for an emergency department (ED) triage. Bispebjerg Hospital has introduced a multidisciplinary team (MT) in the ED activated by the Bispebjerg Early...

  14. Early action to address an emerging wildlife disease

    Science.gov (United States)

    Adams, Michael J.; Harris, M. Camille; Grear, Daniel A.

    2017-02-23

    A deadly fungal pathogen, Batrachochytrium salamandrivorans (Bsal) that affects amphibian skin was discovered during a die-off of European fire salamanders (Salamandra salamandra) in 2014. This pathogen has the potential to worsen already severe worldwide amphibian declines. Bsal is a close relative to another fungal disease known as Batrachochytrium dendrobatidis (Bd). Many scientists consider Bd to be the greatest threat to amphibian biodiversity of any disease because it affects a large number of species and has the unusual ability to drive species and populations to extinction.Although not yet detected in the United States, the emergence of Bsal could threaten the salamander population, which is the most diverse in the world. The spread of Bsal likely will lead to more State and federally listed threatened or endangered amphibian species, and associated economic effects.Because of the concern expressed by resource management agencies, the U.S. Geological Survey (USGS) has made Bsal and similar pathogens a priority for research.

  15. The emergence and early evolution of biological carbon-fixation.

    Science.gov (United States)

    Braakman, Rogier; Smith, Eric

    2012-01-01

    The fixation of CO₂ into living matter sustains all life on Earth, and embeds the biosphere within geochemistry. The six known chemical pathways used by extant organisms for this function are recognized to have overlaps, but their evolution is incompletely understood. Here we reconstruct the complete early evolutionary history of biological carbon-fixation, relating all modern pathways to a single ancestral form. We find that innovations in carbon-fixation were the foundation for most major early divergences in the tree of life. These findings are based on a novel method that fully integrates metabolic and phylogenetic constraints. Comparing gene-profiles across the metabolic cores of deep-branching organisms and requiring that they are capable of synthesizing all their biomass components leads to the surprising conclusion that the most common form for deep-branching autotrophic carbon-fixation combines two disconnected sub-networks, each supplying carbon to distinct biomass components. One of these is a linear folate-based pathway of CO₂ reduction previously only recognized as a fixation route in the complete Wood-Ljungdahl pathway, but which more generally may exclude the final step of synthesizing acetyl-CoA. Using metabolic constraints we then reconstruct a "phylometabolic" tree with a high degree of parsimony that traces the evolution of complete carbon-fixation pathways, and has a clear structure down to the root. This tree requires few instances of lateral gene transfer or convergence, and instead suggests a simple evolutionary dynamic in which all divergences have primary environmental causes. Energy optimization and oxygen toxicity are the two strongest forces of selection. The root of this tree combines the reductive citric acid cycle and the Wood-Ljungdahl pathway into a single connected network. This linked network lacks the selective optimization of modern fixation pathways but its redundancy leads to a more robust topology, making it more

  16. The emergence and early evolution of biological carbon-fixation.

    Directory of Open Access Journals (Sweden)

    Rogier Braakman

    Full Text Available The fixation of CO₂ into living matter sustains all life on Earth, and embeds the biosphere within geochemistry. The six known chemical pathways used by extant organisms for this function are recognized to have overlaps, but their evolution is incompletely understood. Here we reconstruct the complete early evolutionary history of biological carbon-fixation, relating all modern pathways to a single ancestral form. We find that innovations in carbon-fixation were the foundation for most major early divergences in the tree of life. These findings are based on a novel method that fully integrates metabolic and phylogenetic constraints. Comparing gene-profiles across the metabolic cores of deep-branching organisms and requiring that they are capable of synthesizing all their biomass components leads to the surprising conclusion that the most common form for deep-branching autotrophic carbon-fixation combines two disconnected sub-networks, each supplying carbon to distinct biomass components. One of these is a linear folate-based pathway of CO₂ reduction previously only recognized as a fixation route in the complete Wood-Ljungdahl pathway, but which more generally may exclude the final step of synthesizing acetyl-CoA. Using metabolic constraints we then reconstruct a "phylometabolic" tree with a high degree of parsimony that traces the evolution of complete carbon-fixation pathways, and has a clear structure down to the root. This tree requires few instances of lateral gene transfer or convergence, and instead suggests a simple evolutionary dynamic in which all divergences have primary environmental causes. Energy optimization and oxygen toxicity are the two strongest forces of selection. The root of this tree combines the reductive citric acid cycle and the Wood-Ljungdahl pathway into a single connected network. This linked network lacks the selective optimization of modern fixation pathways but its redundancy leads to a more robust topology

  17. Sowing on the emergence and early development of seedlings o baru

    Directory of Open Access Journals (Sweden)

    Alan Mario Zuffo

    2014-09-01

    Full Text Available The objective of this work to evaluate the influence of the position of baru seeds, the emergence and early seedling development. The test was conducted in a greenhouse experiment in randomized blocks, with five treatments (seeding position, with four replications, positions were: A - Hilo up, B - hilo down C - hilum and raphe aside, D - horizontal raphe up, E - horizontal raphe down. It was observed that the seeds deposited at the position B (heel down provided better emergence and seedling development. We evaluated the emergence, speed of emergence index, plant height, stem diameter, root length, dry mass of air, root dry weight, relative AP/DC, FSPA/FSR and Dickson quality index. The emergence and early seedling development baru were influenced by sowing position. The seeds deposited with the hilum down provided better results.

  18. Emerging treatment strategies for trauma-induced coagulopathy.

    Science.gov (United States)

    Sorensen, B; Fries, D

    2012-01-01

    Trauma-induced coagulopathy has a multifactorial aetiology. Coagulopathy is related to blood loss including consumption of clotting factors and platelets and haemodilution. Additionally hyperfibrinolysis, hypothermia, acidosis and metabolic changes affect the coagulation system. This is a review of pathophysiology and new treatment strategies for trauma-induced coagulopathy. Paradigms are actively changing and there is still a shortage of data. The aim of any haemostatic therapy is to control bleeding and minimize blood loss and transfusion requirements. Transfusion of allogeneic blood products as well as trauma-induced coagulopathy cause increased morbidity and mortality. Current opinion is based on present studies and results from small case series, combined with findings from experimental studies in animals, in vitro studies and expert opinions, as opposed to large, randomized, placebo-controlled studies. A summary of new and emerging strategies, including medical infusion and blood products, to beneficially manipulate the coagulation system in the critically injured patient is suggested. Future treatment of trauma-induced coagulopathy may be based on systemic antifibrinolytics, local haemostatics and individualized point-of-care-guided rational use of coagulation factor concentrates such as fibrinogen, prothrombin complex concentrate, recombinant factor VIIa and factor XIII. The authors speculate that timely and rational use of coagulation factor concentrates will be more efficacious and safer than ratio-driven use of transfusion packages of allogeneic blood products. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  19. Hydrochlorothiazide Induced Lichen Planus in the Emergency Department.

    Science.gov (United States)

    Sin, Billy; Miller, Morgan; Chew, Edward

    2017-04-01

    Lichen planus (LP) is a mucocutaneous inflammatory disease that involves papulosquamous eruption of the skin, scalp, nails, and mucous membranes. This uncommon condition has a higher prevalence in African Americans and females. Women accounts for 50% of cutaneous LP (CLP) and 60% to 75% of oral LP (OLP) cases. Diagnosis is centered around clinical presentation. Patient evaluation requires a comprehensive physical examination to identify any potential sites of involvement. LP is usually described by the "Six P's": planar, purple, polygonal, pruritic, papules, and plaques. Drug-induced LP, or lichenoid drug reactions, is uncommon and usually indiscernible from other forms of LP. Lichenoid drug reactions exhibit parakeratosis, dermal infiltrates of eosinophils, or perivascular lymphocytic infiltrates affecting the reticular dermis. An extended time interval between the initiation of drug to the onset of symptoms usually does not exclude potential diagnosis of a lichenoid drug reaction. We describe a case of hydrochlorothiazide-induced LP without prolonged exposure to sunlight diagnosed in the emergency department (ED). In this case, a pharmacist-conducted medication reconciliation played an integral role in accurately recognizing this adverse drug reaction. Our case report adds to the limited available literature on the topic, most of which originated more than 30 years ago.

  20. Cyclophosphamide-induced early cardiotoxicity: comparison of ECG ...

    African Journals Online (AJOL)

    Cyclophosphamide-induced early cardiotoxicity: comparison of ECG changes and disorders in adult and senile rats. Ismail M Abdel-Nabi, Mohamed Alaa Omran. Abstract. Egyptian Journal of Biology Vol.1 1999: 1-15. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD ...

  1. Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study.

    Science.gov (United States)

    Aroke, Edwin N; Crawford, Sybil L; Dungan, Jennifer R

    Up to 55% of patients who are administered ketamine experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury; however, to date, no studies have investigated genetic association of ketamine-induced EP in healthy patients. The aim of the study was to investigate the feasibility and sample sizes required to explore the relationship between CYP2B6*6 and GRIN2B single-nucleotide polymorphisms and ketamine-induced EP. This cross-sectional, pharmacogenetic candidate, gene pilot study recruited 75 patients having minor elective outpatient surgeries. EP was measured with the Clinician Administered Dissociative State Scale. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 and rs1806191) single-nucleotide polymorphisms and ketamine-induced EP occurrence and severity were tested using logistic and linear regression. Forty-seven patients (63%) received ketamine and were genotyped, and 40% of them experienced EP. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p > .10). Exploratory analysis of nongenotype models containing age, ketamine dose, duration of anesthesia, and time from ketamine administration to assessment for EP significantly predicted EP occurrence (p = .001) and severity (p = .007). This pilot study demonstrates feasibility for implementing a pharmacogenetic study in a clinical setting, and we estimate that between 380 and 570 cases will be needed to adequately power future genetic association studies. Younger age, higher dose, and longer duration of anesthesia significantly predicted EP occurrence and severity among our pilot sample. Although the small sample size limited our ability to demonstrate significant genotype differences, we generated effect sizes, sample size estimates, and nongenetic covariates information in order to support future pharmacogenetic study design for evaluating this adverse event.

  2. Ragweed-induced allergic rhinoconjunctivitis: current and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Ihler F

    2015-02-01

    Full Text Available Friedrich Ihler, Martin CanisDepartment of Otorhinolaryngology, University Medical Center Göttingen, Göttingen, GermanyAbstract: Ragweed (Ambrosia spp. is an annually flowering plant whose pollen bears high allergenic potential. Ragweed-induced allergic rhinoconjunctivitis has long been seen as a major immunologic condition in Northern America with high exposure and sensitization rates in the general population. The invasive occurrence of ragweed (A. artemisiifolia poses an increasing challenge to public health in Europe and Asia as well. Possible explanations for its worldwide spread are climate change and urbanization, as well as pollen transport over long distances by globalized traffic and winds. Due to the increasing disease burden worldwide, and to the lack of a current and comprehensive overview, this study aims to review the current and emerging treatment options for ragweed-induced rhinoconjunctivitis. Sound clinical evidence is present for the symptomatic treatment of ragweed-induced allergic rhinoconjunctivitis with oral third-generation H1-antihistamines and leukotriene antagonists. The topical application of glucocorticoids has also been efficient in randomized controlled clinical trials. Combined approaches employing multiple agents are common. The mainstay of causal treatment to date, especially in Northern America, is subcutaneous immunotherapy with the focus on the major allergen, Amb a 1. Beyond this, growing evidence from several geographical regions documents the benefit of sublingual immunotherapy. Future treatment options promise more specific symptomatic treatment and fewer side effects during causal therapy. Novel antihistamines for symptomatic treatment are aimed at the histamine H3-receptor. New adjuvants with toll-like receptor 4 activity or the application of the monoclonal anti-immunoglobulin E antibody, omalizumab, are supposed to enhance conventional immunotherapy. An approach targeting toll-like receptor 9 by

  3. Ragweed-induced allergic rhinoconjunctivitis: current and emerging treatment options.

    Science.gov (United States)

    Ihler, Friedrich; Canis, Martin

    2015-01-01

    Ragweed (Ambrosia spp.) is an annually flowering plant whose pollen bears high allergenic potential. Ragweed-induced allergic rhinoconjunctivitis has long been seen as a major immunologic condition in Northern America with high exposure and sensitization rates in the general population. The invasive occurrence of ragweed (A. artemisiifolia) poses an increasing challenge to public health in Europe and Asia as well. Possible explanations for its worldwide spread are climate change and urbanization, as well as pollen transport over long distances by globalized traffic and winds. Due to the increasing disease burden worldwide, and to the lack of a current and comprehensive overview, this study aims to review the current and emerging treatment options for ragweed-induced rhinoconjunctivitis. Sound clinical evidence is present for the symptomatic treatment of ragweed-induced allergic rhinoconjunctivitis with oral third-generation H1-antihistamines and leukotriene antagonists. The topical application of glucocorticoids has also been efficient in randomized controlled clinical trials. Combined approaches employing multiple agents are common. The mainstay of causal treatment to date, especially in Northern America, is subcutaneous immunotherapy with the focus on the major allergen, Amb a 1. Beyond this, growing evidence from several geographical regions documents the benefit of sublingual immunotherapy. Future treatment options promise more specific symptomatic treatment and fewer side effects during causal therapy. Novel antihistamines for symptomatic treatment are aimed at the histamine H3-receptor. New adjuvants with toll-like receptor 4 activity or the application of the monoclonal anti-immunoglobulin E antibody, omalizumab, are supposed to enhance conventional immunotherapy. An approach targeting toll-like receptor 9 by synthetic cytosine phosphate-guanosine oligodeoxynucleotides promises a new treatment paradigm that aims to modulate the immune response, but it has

  4. RED Alert – Early warning or detection of global re-emerging infectious disease (RED)

    Energy Technology Data Exchange (ETDEWEB)

    Deshpande, Alina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-07-13

    This is the PDF of a presentation for a webinar given by Los Alamos National Laboratory (LANL) on the early warning or detection of global re-emerging infectious disease (RED). First, there is an overview of LANL biosurveillance tools. Then, information is given about RED Alert. Next, a demonstration is given of a component prototype. RED Alert is an analysis tool that can provide early warning or detection of the re-emergence of an infectious disease at the global level, but through a local lens.

  5. Early micronutrient supplementation protects against early stress-induced cognitive impairments.

    Science.gov (United States)

    Naninck, Eva F G; Oosterink, J Efraim; Yam, Kit-Yi; de Vries, Lennart P; Schierbeek, Henk; van Goudoever, Johannes B; Verkaik-Schakel, Rikst-Nynke; Plantinga, Josèe A; Plosch, Torsten; Lucassen, Paul J; Korosi, Aniko

    2017-02-01

    Early-life stress (ES) impairs cognition later in life. Because ES prevention is problematic, intervention is needed, yet the mechanisms that underlie ES remain largely unknown. So far, the role of early nutrition in brain programming has been largely ignored. Here, we demonstrate that essential 1-carbon metabolism-associated micronutrients (1-CMAMs; i.e., methionine and B vitamins) early in life are crucial in programming later cognition by ES. ES was induced in male C57Bl/6 mice from postnatal d (P)2-9. 1-CMAM levels were measured centrally and peripherally by using liquid chromatography-mass spectroscopy. Next, we supplemented the maternal diet with 1-CMAM only during the ES period and studied cognitive, neuroendocrine, neurogenic, transcriptional, and epigenetic changes in adult offspring. We demonstrate that ES specifically reduces methionine in offspring plasma and brain. Of note, dietary 1-CMAM enrichment during P2-9 restored methionine levels and rescued ES-induced adult cognitive impairments. Beneficial effects of this early dietary enrichment were associated with prevention of the ES-induced rise in corticosterone and adrenal gland hypertrophy did not involve changes in maternal care, hippocampal volume, neurogenesis, or global/Nr3c1-specific DNA methylation. In summary, nutrition is important in brain programming by ES. A short, early supplementation with essential micronutrients can already prevent lasting effects of ES. This concept opens new avenues for nutritional intervention.-Naninck, E. F. G., Oosterink, J. E., Yam, K.-Y., de Vries, L. P., Schierbeek, H., van Goudoever, J. B., Verkaik-Schakel, R.-N., Plantinga, J. A., Plosch, T., Lucassen, P. J., Korosi, A. Early micronutrient supplementation protects against early stress-induced cognitive impairments. © FASEB.

  6. Hypoxia-induced phrenic long-term facilitation: emergent properties.

    Science.gov (United States)

    Devinney, Michael J; Huxtable, Adrianne G; Nichols, Nicole L; Mitchell, Gordon S

    2013-03-01

    As in other neural systems, plasticity is a hallmark of the neural system controlling breathing. One spinal mechanism of respiratory plasticity is phrenic long-term facilitation (pLTF) following acute intermittent hypoxia. Although cellular mechanisms giving rise to pLTF occur within the phrenic motor nucleus, different signaling cascades elicit pLTF under different conditions. These cascades, referred to as Q and S pathways to phrenic motor facilitation (pMF), interact via cross-talk inhibition. Whereas the Q pathway dominates pLTF after mild to moderate hypoxic episodes, the S pathway dominates after severe hypoxic episodes. The biological significance of multiple pathways to pMF is unknown. This review will discuss the possibility that interactions between pathways confer emergent properties to pLTF, including pattern sensitivity and metaplasticity. Understanding these mechanisms and their interactions may enable us to optimize intermittent hypoxia-induced plasticity as a treatment for patients that suffer from ventilatory impairment or other motor deficits. © 2013 New York Academy of Sciences.

  7. Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network.

    Science.gov (United States)

    Cordes, Kristina M; Cookson, Susan T; Boyd, Andrew T; Hardy, Colleen; Malik, Mamunur Rahman; Mala, Peter; El Tahir, Khalid; Everard, Marthe; Jasiem, Mohamad; Husain, Farah

    2017-11-01

    Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security.

  8. Predictors of early arrival at the emergency department in acute ischaemic stroke.

    LENUS (Irish Health Repository)

    Curran, C

    2012-01-31

    BACKGROUND: A requirement of an effective acute stroke service is the early arrival of patients to the hospital emergency department (ED). This will allow the possible use of thrombolytic therapy or other acute interventions within a limited time window. AIMS: We investigated the predictors of early arrival in a single hospital serving a mixed urban and rural catchment area. METHODS: A retrospective review of all case notes for 1 year was performed. RESULTS: Of 105 acute strokes, 91 were cerebral infarcts and a total of 71 cases presenting initially to the ED had timing available for analysis. 39.4% presented within 3 h, and 12.7% were potentially suitable for thrombolysis. Those living closer to the hospital were not more likely to arrive within 3 h (Z = -0.411, p = 0.68). Presenting directly to the hospital by emergency services (or private transport) was significantly associated with early arrival in a univariate comparison (p < 0.001), and in a multivariate model. CONCLUSION: The only independent predictor of early arrival to the ED is direct presentation. Improved public education of the importance of recognition of stroke symptoms and rapid contact with the emergency services will improve the early attendance following acute stroke, allowing increased use of acute stroke treatments.

  9. Bayesian analysis of the astrobiological implications of life's early emergence on Earth.

    Science.gov (United States)

    Spiegel, David S; Turner, Edwin L

    2012-01-10

    Life arose on Earth sometime in the first few hundred million years after the young planet had cooled to the point that it could support water-based organisms on its surface. The early emergence of life on Earth has been taken as evidence that the probability of abiogenesis is high, if starting from young Earth-like conditions. We revisit this argument quantitatively in a bayesian statistical framework. By constructing a simple model of the probability of abiogenesis, we calculate a bayesian estimate of its posterior probability, given the data that life emerged fairly early in Earth's history and that, billions of years later, curious creatures noted this fact and considered its implications. We find that, given only this very limited empirical information, the choice of bayesian prior for the abiogenesis probability parameter has a dominant influence on the computed posterior probability. Although terrestrial life's early emergence provides evidence that life might be abundant in the universe if early-Earth-like conditions are common, the evidence is inconclusive and indeed is consistent with an arbitrarily low intrinsic probability of abiogenesis for plausible uninformative priors. Finding a single case of life arising independently of our lineage (on Earth, elsewhere in the solar system, or on an extrasolar planet) would provide much stronger evidence that abiogenesis is not extremely rare in the universe.

  10. [Clinical study of induced abortion of early-early pregnancy: an analysis of 10, 404 cases].

    Science.gov (United States)

    Kang, Jian; Wang, Xue-fen; Zhang, Li; Liu, Jian-hua

    2012-01-03

    To evaluate the advantages and disadvantages of early-early pregnancy induced abortion (EPIA). A total of 10 404 cases of EPIA performed at our hospital from January 1993 to December 2003 were retrospectively analyzed and compared with 9434 cases of common induced abortion (CIA). The amount of hemorrhage and operative duration, degree of pain, rate of induced-abortion syndrome, rate of incomplete abortion, menstrual changes and post-operative onset of Asherman's syndrome were observed and compared between 2 groups. The average age, ratio of parous cases, ratio of the cases of first-pregnancy induced abortion were not different between 2 groups (P > 0.05). The amount of hemorrhage bleeding ((4.9 ± 3.2) ml), operative duration ((90.3 ± 12.4) s), degree of pain, rate of induced-abortion syndrome, menstrual changes and the rate of Asherman's syndrome in the EPIA group were all significantly less than those in the CIA group (P abortion (0.44%) in the EPIA group was significantly higher than that (0.21%) in the CIA group (P abortion stays high.

  11. A Methane-Rich Early Mars: Implications for Habitability and the Emergence of Life

    Science.gov (United States)

    Wong, Michael L.; Friedson, Andrew James; Willacy, Karen; Shia, Run-Lie; Yung, Yuk; Russell, Michael J.

    2017-10-01

    We investigate the radiation and chemistry of a ~4.0 Ga, CH4-rich martian atmosphere in an effort to assess whether or not Mars was once habitable and suitable for the emergence of life. High atmospheric CH4 may be consistent with a mantle that does not reach the requisite pressure (24 GPa) and temperature (1900 K) for the silicate spinel-to-perovskite transition (Dale et al., 2012; McCammon, 1997; Wadhwa, 2001; Wood et al., 2006). Impact degassing from chondritic material can also contribute substantial amounts of CH4 to the atmosphere (Schaefer and Fegley, 2007). CH4 plays an important role in atmospheric radiation. Atmospheric models have demonstrated that a purely CO2 atmosphere, even one as massive as 7 bars, is incapable of heating Mars above an annual-mean surface temperature of 273 K (Forget et al., 2013), although recent studies show that recurring wet states could have been induced in an H2-rich atmosphere (Batalha et al., 2015, 2016). We show that CH4 alone is insufficient to warm early Mars above freezing—in fact it produces an anti-greenhouse effect—but it substantially raises middle atmospheric temperatures. We determine whether or not such high temperatures could prolong the photochemical lifetime of SO2, another potent greenhouse gas. We use RC1D, a non-gray 1-D radiative-convective equilibrium model, to calculate the atmospheric thermal structure consistent with the radiative heating and cooling associated with the composition computed at each chemical model time step. KINETICS, the Caltech/JPL chemistry transport model (e.g. Nair et al., 1994), determines the chemical makeup of the atmosphere, evaluating steady-state chemical profiles and the synthesis of astrobiologically relevant molecules. H2O is in vapor pressure equilibrium at the surface. We consider conditions forced by the faint-young Sun’s spectrum and luminosity. By coupling RC1D and KINETICS, we are able to paint a more realistic picture of Mars’s early climate, calculating the

  12. Nurse-administered early warning score system can be used for emergency department triage

    DEFF Research Database (Denmark)

    Christensen, Dorthea; Jensen, Nanna Martin; Maaløe, Rikke

    2011-01-01

    Studies have shown that early warning score systems can identify in-patients at high risk of catastrophic deterioration and this may possibly be used for an emergency department (ED) triage. Bispebjerg Hospital has introduced a multidisciplinary team (MT) in the ED activated by the Bispebjerg Early...... Warning Score (BEWS). The BEWS is calculated on the basis of respiratory frequency, pulse, systolic blood pressure, temperature and level of consciousness. The aim of this study is to evaluate the ability of the BEWS to identify critically ill patients in the ED and to examine the feasibility of using...

  13. Modeling Polymorphemic Word Recognition: Exploring Differences Among Children With Early-Emerging and Late-Emerging Word Reading Difficulty.

    Science.gov (United States)

    Kearns, Devin M; Steacy, Laura M; Compton, Donald L; Gilbert, Jennifer K; Goodwin, Amanda P; Cho, Eunsoo; Lindstrom, Esther R; Collins, Alyson A

    2016-07-01

    Comprehensive models of derived polymorphemic word recognition skill in developing readers, with an emphasis on children with reading difficulty (RD), have not been developed. The purpose of the present study was to model individual differences in polymorphemic word recognition ability at the item level among 5th-grade children (N = 173) oversampled for children with RD using item-response crossed random-effects models. We distinguish between two subtypes of RD children with word recognition problems, those with early-emerging RD and late-emerging RD. An extensive set of predictors representing item-specific knowledge, child-level characteristics, and word-level characteristics were used to predict item-level variance in polymorphemic word recognition. Results indicate that item-specific root word recognition and word familiarity; child-level RD status, morphological awareness, and orthographic choice; word-level frequency and root word family size; and the interactions between morphological awareness and RD status and root word recognition and root transparency predicted individual differences in polymorphemic word recognition item performance. Results are interpreted within a multisource individual difference model of polymorphemic word recognition skill spanning item-specific, child-level, and word-level knowledge. © Hammill Institute on Disabilities 2014.

  14. Persistent Language Delay Versus Late Language Emergence in Children With Early Cochlear Implantation

    Science.gov (United States)

    Nicholas, Johanna; Tobey, Emily; Davidson, Lisa

    2016-01-01

    Purpose The purpose of the present investigation is to differentiate children using cochlear implants (CIs) who did or did not achieve age-appropriate language scores by midelementary grades and to identify risk factors for persistent language delay following early cochlear implantation. Materials and Method Children receiving unilateral CIs at young ages (12–38 months) were tested longitudinally and classified with normal language emergence (n = 19), late language emergence (n = 22), or persistent language delay (n = 19) on the basis of their test scores at 4.5 and 10.5 years of age. Relative effects of demographic, audiological, linguistic, and academic characteristics on language emergence were determined. Results Age at CI was associated with normal language emergence but did not differentiate late emergence from persistent delay. Children with persistent delay were more likely to use left-ear implants and older speech processor technology. They experienced higher aided thresholds and lower speech perception scores. Persistent delay was foreshadowed by low morphosyntactic and phonological diversity in preschool. Logistic regression analysis predicted normal language emergence with 84% accuracy and persistent language delay with 74% accuracy. Conclusion CI characteristics had a strong effect on persistent versus resolving language delay, suggesting that right-ear (or bilateral) devices, technology upgrades, and improved audibility may positively influence long-term language outcomes. PMID:26501740

  15. Detection of early caries by laser-induced breakdown spectroscopy

    Science.gov (United States)

    Sasazawa, Shuhei; Kakino, Satoko; Matsuura, Yuji

    2015-07-01

    To improve sensitivity of dental caries detection by laser-induced breakdown spectroscopy (LIBS) analysis, it is proposed to utilize emission peaks in the ultraviolet. We newly focused on zinc whose emission peaks exist in ultraviolet because zinc exists at high concentration in the outer layer of enamel. It was shown that by using ratios between heights of an emission peak of Zn and that of Ca, the detection sensitivity and stability are largely improved. It was also shown that early caries are differentiated from healthy part by properly setting a threshold in the detected ratios. The proposed caries detection system can be applied to dental laser systems such as ones based on Er:YAG-lasers. When ablating early caries part by laser light, the system notices the dentist that the ablation of caries part is finished. We also show the intensity of emission peaks of zinc decreased with ablation with Er:YAG laser light.

  16. Do either early warning systems or emergency response teams improve hospital patient survival? A systematic review.

    Science.gov (United States)

    McNeill, G; Bryden, D

    2013-12-01

    For critical care to be effective it must have a system in place to achieve optimal care for the deteriorating ward patient. To systematically review the available literature to assess whether either early warning systems or emergency response teams improve hospital survival. In the event of there being a lack of evidence regarding hospital survival, secondary outcome measures were considered (unplanned ICU admissions, ICU mortality, length of ICU stay, length of hospital stay, cardiac arrest rates). The Ovid Medline, EMBASE, CINAHL, Web of Science, Cochrane library and NHS databases were searched in September 2012 along with non-catalogued resources for papers examining the effect of early warning systems or emergency response teams on hospital survival. Inclusion criteria were original clinical trials and comparative studies in adult inpatients that assessed either an early warning system or emergency response team against any of the predefined outcome measures. Exclusion criteria were previous systematic reviews, non-English abstracts and studies incorporating paediatric data. Studies were arranged in to sections focusing on the following interventions: Early warning systems - Single parameter systems - Aggregate weighted scoring systems (AWSS) Emergency response teams - Medical emergency teams - Multidisciplinary outreach services . In each section an appraisal of the level of evidence and a recommendation has been made using the SIGN grading system. 43 studies meeting the review criteria were identified and included for analysis. 2 studies assessed single parameter scoring systems and 4 addressed aggregate weighted scoring systems. A total of 20 studies examined medical emergency teams and 22 studies examined multidisciplinary outreach teams. The exclusion of non English studies and those including paediatric patients does limit the applicability of this review. Much of the available evidence is of poor quality. It is clear that a 'whole system' approach

  17. Characteristics of patients and families who make early return visits to the pediatric emergency department

    Directory of Open Access Journals (Sweden)

    Logue EP

    2013-06-01

    Full Text Available Erin Patricia Logue,1 Samina Ali,2,3 Judith Spiers,4 Amanda S Newton,2,3 Janice A Lander4 1 Alberta Health Services, 2Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 3Women and Children’s Health Research Institute, 4Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada Objectives: The primary objective of this study was to identify reasons why parents make early return visits, within 72 hours of discharge from a tertiary care pediatric emergency department (PED. A secondary objective was to investigate associated demographic and diagnostic variables. Methods: A survey was conducted with a convenience sample of parents of children returning to the PED within 72 hours of discharge. A chart review was also completed for consented survey participants. Recruitment occurred from September 2005 to August 2006 at the Stollery Children's Hospital, Edmonton, Alberta, Canada. Results: A total of 264 parents were approached to participate. Overall, 231 surveys were returned and 212 (92% charts were reviewed. The overall rate of early return during the study period was 5.4%. More than half of parents stated that they returned because their child's condition worsened and many parents (66.7% reported feeling stressed. Patients were typically under 6 years of age (67.4%, and most frequently diagnosed with infectious diseases (38.0%. Patients triaged with the Canadian Emergency Department Triage and Acuity Scale (CTAS as CTAS 2 (emergent for initial visits were more likely to be admitted on return, regardless of age (P < 0.001. Conclusion: Variables associated with early returns included young age, diagnosis, triage acuity, and parental stress. Future variable definition should include a deeper exploration of modifiable factors such as parental stress and patient education. These next steps may help direct interventions and resources to address needs in this group and possibly pre-empt the need to return

  18. An analysis of the early-warning system in emerging markets for reducing the financial crisis

    Science.gov (United States)

    Shen, Xiangguang; Song, Xiaozhong

    2009-07-01

    The large number of financial crises in emerging markets over the past ten years has left many observers, both from academia and financial institutions, puzzled by an apparent lack of homogenous causal relations between endogenous economic variables and the bursting of large financial shocks. The frequency of financial crises in the last 20 years can be attributed to the lack of a comprehensive theory of financial regulation to guide policy makers. Existing theories fail to define the range of regulatory models, the causes of regulatory failure, and how to measure and prevent it. Faulty design of regulatory models, and the lack of ongoing performance monitoring incorporating early warning systems, is disrupting economic and social development. The main aim of this article is to propose an early warning system (EWS) which purposes issuing warning signal against the possible financial crisis in the emerging market, and makes the emerging market survived the first wave of the crisis be able to continue their operation in the following years.

  19. Early economic evaluation of emerging health technologies: protocol of a systematic review

    Science.gov (United States)

    2014-01-01

    Background The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. Methods/design This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to

  20. Success of applying early goal-directed therapy for septic shock patients in the emergency department

    Directory of Open Access Journals (Sweden)

    Worapratya P

    2016-01-01

    Full Text Available Panita Worapratya,1 Apisit Wanjaroenchaisuk,2 Jutharat Joraluck,3 Prasit Wuthisuthimethawee1 1Department of Emergency Medicine, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Songkhla, 2Emergency Department, Samitivej Thonburi Hospital, Bangkok, 3Emergency Department, Hatyai Hospital, Hatyai, Songkhla, Thailand Background: Since early goal-directed therapy (EGDT became standard care in severe sepsis and septic shock patients in intensive care units many years ago, we suppose that the survival rate of severe sepsis and septic shock patients improves if the resuscitative procedure is quickly implemented and is initiated in the emergency room. Objective: We aimed at recording emergency department time to improve our patient care system as well as determine the rate at which EGDT goals can be achieved. The second analysis is to find out how much we can improve the survival rate. Methods: This was a prospective observational study in an emergency room setting at a tertiary care facility where EGDT was applied for resuscitation of severe sepsis and septic shock patients. The data recorded were the initial vital signs, APACHE II (Acute Physiology and Chronic Health Evaluation II score, SAP II (Simplified Acute Physiology II score, SOFA (Sequential Organ Failure Assessment score, time at which EGDT goals were achieved (central venous oxygen saturation [Scvo2] >70%, initial and final diagnosis, and outcome of treatment. The t-test and Mann–Whitney U-test were used to compare between the achieved goal and nonachieved goal groups. Results: There were 63 cases of severe sepsis in the study period. Only 55 patients submitted a signed consent form and had central line insertion. Twenty-eight (50.9% cases were male. Thirty-nine (70.9% patients achieved the goal, and the mean SAP II score was 8. There were no statistically significant differences between the two groups (P-value =0.097. Thirty of the 39 patients (70.9% survived in

  1. [Prognostic factors of early 30-day mortality in elderly patients admitted to an emergency department].

    Science.gov (United States)

    Morales Erazo, Alexander; Cardona Arango, Doris

    The main aim of this study was to identify the variables related to early mortality in the elderly at the time of admission to the emergency department. Using probability sampling, the study included patients 60 years old or older of both genders who were admitted for observation to the emergency department of the University Hospital of Nariño, ¿Colombia? in 2015. Using a questionnaire designed for this study, some multidimensional features that affect the health of the elderly were collected (demographic, clinical, psychological, functional, and social variables). The patients were then followed-up for 30 days in order to determine the mortality rate during this time. Univariate and multivariate logistic regressions and survival analysis were performed. Data were collected from 246 patients, with a mean age of 75.27 years and the majority female. The 30-day mortality rate was 15%. The variables most associated with death were: being female, temperature problems, initial diagnosis of neoplasia, and unable to walk independently in the emergency department. It is possible to determine the multidimensional factors present in the older patient admitted to an emergency department that could affect their 30-day mortality prognosis. and which should be intervened. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Radiological Emergency Preparedness after the Early Phase of an Accident : Focusing on an Air Contamination Event

    International Nuclear Information System (INIS)

    Jeong, Hyo Joon; Hwang, Won Tae; Kim, Eun Han; Han, Moon Hee

    2010-01-01

    Toxic materials in an urban area can be caused by a variety of events, such as accidental releases on industrial complexes, accidents during the transportation of hazardous materials and intentional explosions. Most governments around the world and their citizens have become increasingly worried about intentional accidents in urban area after the 911 terrorist attack in the United States of America. Even though there have been only a few attempted uses of Radiological Dispersal Devices (RDDs), accidental releases have occurred many times at commercial nuclear power plants and nuclear waste disposal sites. When an intentional release of radioactive materials occurs in an urban area, air quality for radioactive materials in the environment is of great importance to take action for countermeasures and environmental risk assessments. Atmospheric modeling is part of the decision making tasks and that it is particularly important for emergency managers as they often need to take actions quickly on very inadequate information(1). A simple model such as HOTSPOT required wind direction and source term would be enough to support the decision making in the early phase of an accident, but more sophisticated atmospheric modeling is required to adjust decontamination area and relocation etc after the early phase of an accidental event. In this study, we assume an explosion of 137 Cs using RDDs in the metropolitan area of Soul, South Korea. California Puff Model (CALPUFF) is used to calculate an atmospheric dispersion and transport for 137 Cs. Atmospheric dispersion and quantitative radiological risk analysis for 137 Cs were performed assuming an intentional explosion in the metropolitan area of Soul, South Korea after the early phase of emergency. These kinds of atmospheric modeling and risk analysis could provide a means for decision makers to take action on important issues such as the cleanup of the contaminated area and countermeasures to protect the public caused by

  3. Chemotherapy-induced irreversible alopecia in early breast cancer patients.

    Science.gov (United States)

    Kim, Gun Min; Kim, Sanghwa; Park, Hyung Seok; Kim, Jee Ye; Nam, Sanggen; Park, Seho; Kim, Seung Il; Kim, DoYoung; Sohn, Joohyuk

    2017-06-01

    The purpose of this work is to determine the prevalence of chemotherapy-induced irreversible alopecia (CIIA), which is defined as an alopecia that exists at least 6 months after completion of chemotherapy and factors affecting CIIA in early breast cancer patients. We performed a cross-sectional study. We retrospectively identified breast cancer patients who had received AC (Adriamycin, Cyclophosphamide) or AC-T (AC followed by Taxane) as neoadjuvant or adjuvant chemotherapy. We conducted questionnaire survey regarding alopecia and measured hair density using phototrichogram. From February 2015 to May 2015, among 265 patients who responded properly to the questionnaire, the women who answered they had severe alopecia (alopecia > 50% of scalp) were 19 patients (7.2%). AC-only and AC-T treated patients reported severe alopecia in 2.7% and 10.5%, respectively, which were significantly different (p < 0.001). Mean hair density was 75 hair/cm 2 (range 42-112) and 75.2/cm 2 (range 48.3-102) on occipital area and vertex area, respectively. Hair loss was the most frequent in parietal area (42.6%). Half of total patients (46%) and 73% of CIIA patients regarded that their hair became thinner after chemotherapy CONCLUSIONS: We found that significant proportion of early breast cancer patients were suffering from severe CIIA, especially when they had been treated with AC followed by taxane regimen.

  4. Early-life family structure and microbially induced cancer risk.

    Directory of Open Access Journals (Sweden)

    Martin J Blaser

    2007-01-01

    Full Text Available Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men.We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative, belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0 among those in a sibship of seven or more individuals than in a sibship of between one and three persons.These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.

  5. Workshop "Emerging risks and early warning systems" : deelproject 1.2 : miniconferentie over roegtijdig signalering en waarschuwingssystemen

    NARCIS (Netherlands)

    Koenderink, N.J.J.P.; Kreft, F.

    2007-01-01

    This report is the result of the workshop “Emerging risks and early warning system” held in Wageningen, the Netherlands on October the 19th 2006. The workshop is part of the project “Emerging risks in Dutch food chains”. The purpose of this project is to develop a procedure to identify potential

  6. On Becoming Batman: An Ethnographic Examination of Hero Imagery in Early-Career Residential Life Emergency Management

    Science.gov (United States)

    Molina, Danielle K.

    2016-01-01

    Emergency response is an essential function of all residential life staff, but particularly for resident assistants serving on the front line. This organizational ethnography examined the role that professional identity played for early-career residential life practitioners engaged in emergency management. The data elucidated heroism as a…

  7. Sudden early-morning awakening impairs immediate tactical planning in a changing 'emergency' scenario.

    Science.gov (United States)

    Horne, Jim; Moseley, Robert

    2011-06-01

    This was a realistic military-type exercise assessing unexpected, abrupt early-morning awakening effects on immediate 'executive function' and the ability to comprehend and deal with a sudden emergency under a changing situation. Twenty (average age 21years) healthy, highly motivated junior officer reservists were assigned randomly to two equal, independent groups, unforewarned as to what would happen. The experimental group was woken abruptly at 03:00h (plan of engagement with minimal loss of resources, to be completed within 15min. A control group slept until 07:30h; they were then presented with the identical emergency 1h later. Participants worked individually, under time pressure, receiving written information, map and other details, all containing relevant, irrelevant and misleading information. Halfway through, they were given (unexpectedly) a critical update necessitating a change of tactics. Performance was scored blind by instructors, under five categories. Eight of the experimental group versus three controls failed overall, with significant group differences on three specific categories relying on flexible decision-making: 'identification of available cover', 'use of available assets' and 'extraction of relevant from irrelevant information'. Other, logical and highly trained skills were unimpaired. Ours was a 'worst case scenario', combining short sleep, circadian 'trough' and sleep inertia, all of which differentiated the two groups, unlike typical laboratory studies. Nevertheless, it was relevant to real-life situations involving highly motivated, trained individuals making critical innovative decisions in the early morning versus the normal waking day. © 2010 European Sleep Research Society.

  8. Emerging targets for treating sulfur mustard-induced injuries.

    Science.gov (United States)

    Ahmad, Shama; Ahmad, Aftab

    2016-06-01

    Sulfur mustard (SM; bis-(2-chlororethyl) sulfide) is a highly reactive, potent warfare agent that has recently reemerged as a major threat to military and civilians. Exposure to SM is often fatal, primarily due to pulmonary injuries and complications caused by its inhalation. Profound inflammation, hypercoagulation, and oxidative stress are the hallmarks that define SM-induced pulmonary toxicities. Despite advances, effective therapies are still limited. This current review focuses on inflammatory and coagulation pathways that influence the airway pathophysiology of SM poisoning and highlights the complexity of developing an effective therapeutic target. © 2016 New York Academy of Sciences.

  9. Emerging Early Actions to Bend the Curve in Sub-Saharan Africa's Nutrition Transition.

    Science.gov (United States)

    Haggblade, Steven; Duodu, Kwaku G; Kabasa, John D; Minnaar, Amanda; Ojijo, Nelson K O; Taylor, John R N

    2016-06-01

    Sub-Saharan Africa is the last region to undergo a nutrition transition and can still avoid its adverse health outcomes. The article explores emerging responses to "bend the curve" in sub-Saharan Africa's nutrition transition to steer public health outcomes onto a healthier trajectory. Early responses in 3 countries at different stages of food system transformation are examined: South Africa-advanced, Ghana-intermediate, and Uganda-early. By comparing these with international experience, actions are proposed to influence nutrition and public health trajectories as Africa's food systems undergo rapid structural change. Arising from rapid urbanization and diet change, major public health problems associated with overweight are taking place, particularly in South Africa and among adult women. However, public health responses are generally tepid in sub-Saharan Africa. Only in South Africa have policy makers instituted extensive actions to combat overweight and associated noncommunicable diseases through regulation, education, and public health programs. Elsewhere, in countries in the early and middle stages of transition, public health systems continue to focus their limited resources primarily on undernutrition. Related pressures on the supply side of Africa's food systems are emerging that also need to be addressed. Three types of intervention appear most feasible: maternal and child health programs to simultaneously address short-term undernutrition problems while at the same time helping to reduce future tendencies toward overweigh; regulatory and fiscal actions to limit access to unhealthy foods; and modernization of Africa's agrifood food system through job skills training, marketing reforms, and food industry entrepreneurship. © The Author(s) 2016.

  10. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia

    Science.gov (United States)

    Taylor, Norman E.; Chemali, Jessica J.; Brown, Emery N.; Solt, Ken

    2012-01-01

    BACKGROUND A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia. METHODS In adult rats, we tested the effects of chloro-APB (D1 agonist) and quinpirole (D2 agonist) on time to emergence from isoflurane general anesthesia. We then performed a dose–response study to test for chloro-APB-induced restoration of righting during continuous isoflurane anesthesia. SCH-23390 (D1 antagonist) was used to confirm that the effects induced by chloro-APB are specifically mediated by D1 receptors. In a separate group of animals, spectral analysis was performed on surface electroencephalogram recordings to assess neurophysiological changes induced by chloro-APB and quinpirole during isoflurane general anesthesia. RESULTS Chloro-APB decreased median time to emergence from 330s to 50s. The median difference in time to emergence between the saline control group (n=6) and the chloro-APB group (n = 6) was 222s (95% CI: 77–534s, Mann-Whitney test). This difference was statistically significant (p = 0.0082). During continuous isoflurane anesthesia, chloro-APB dose-dependently restored righting (n = 6) and decreased electroencephalogram delta power (n = 4). These effects were inhibited by pretreatment with SCH-23390. Quinpirole did not restore righting (n = 6) and had no significant effect on the electroencephalogram (n = 4) during continuous isoflurane anesthesia. CONCLUSIONS Activation of D1 receptors by chloro-APB decreases time to emergence from isoflurane anesthesia, and produces behavioral and neurophysiological evidence of arousal during continuous isoflurane anesthesia. These findings suggest that selective activation of a D1 receptor-mediated arousal mechanism is sufficient to induce emergence from isoflurane general

  11. GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy.

    Science.gov (United States)

    Papandreou, Apostolos; McTague, Amy; Trump, Natalie; Ambegaonkar, Gautam; Ngoh, Adeline; Meyer, Esther; Scott, Richard H; Kurian, Manju A

    2016-04-01

    The gamma-aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3-subunit of the gamma-aminobutyric acid type A (GABAA ) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox-Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3-related early-onset epileptic encephalopathy. Our patient presented with neonatal hypotonia and feeding difficulties, then developed pharmacoresistant epileptic encephalopathy, characterized by multiple seizure types from 3 months of age. Electroencephalography demonstrated ictal generalized and interictal multifocal epileptiform abnormalities. Using a SureSelectXT custom multiple gene panel covering 48 early infantile epileptic encephalopathy/developmental delay genes, a novel de novo GABRB3 heterozygous missense mutation, c.860C>T (p.Thr287Ile), was identified and confirmed on Sanger sequencing. GABRB3 is an emerging cause of early-onset epilepsy. Novel genetic technologies, such as whole-exome/genome sequencing and multiple gene panels, will undoubtedly identify further cases, allowing more detailed electroclinical delineation of the GABRB3-related genotypic and phenotypic spectra. © 2015 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

  12. Radiation induced early onset of neuro-cognitive changes

    International Nuclear Information System (INIS)

    Kumar, Mayank; Haridas, Seenu; Gupta, Mamta; Trivedi, Richa; Khushu, Subhash; Manda, Kailash

    2012-01-01

    Exposure to ionizing radiations has been shown to cause many detrimental effects. Primarily, the effects observed are broadly classified into hematopoietic syndrome at lower doses, gastrointestinal syndrome and central nervous system dysfunctions at high doses. However, recent studies reported that even at lower doses, there is an effect seen on the nervous system which can be observed as a decline in cognitive abilities. This has been reported in patients undergoing radiotherapy. The cognitive decline, especially in young patients affects development and has been shown to persist for years after the therapy. Thus, the aim of this study was to study and consolidate the early effects of radiation exposure which result in behavioural alterations and cognitive decline. Since, radiation-induced early changes in behavioural functions are poorly understood, therefore, the present investigation aimed to conceptualize and design behavioural test batteries in order to systematically study the immediate alterations in behavioural function following irradiation with a-rays. The behavioural alterations were correlated to changes in the different area of brain like hippocampus, thalamus, hypothalamus and corpus callosum using Diffusion Tensor Imaging (DTI) studies. Present study reported profound changes in behaviour, as well as alterations in the morphology of the brain tissue as perceived by DTI, 48 hours after exposure to ionizing radiations. These changes need to be correlated and clarified further to understand the mechanisms behind the cognitive dysfunctions occurring immediately after radiation exposure as well as to find out a therapeutic window to counteract or reduce the effect of long term cognitive changes following irradiation. (author)

  13. Induced Pluripotent Stem Cells: Emerging Techniques for Nuclear Reprogramming

    Science.gov (United States)

    Han, Ji Woong

    2011-01-01

    Abstract Introduction of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, can successfully reprogram somatic cells into embryonic stem (ES)-like cells. These cells, which are referred to as induced pluripotent stem (iPS) cells, closely resemble embryonic stem cells in genomic, cell biologic, and phenotypic characteristics, and the creation of these special cells was a major triumph in cell biology. In contrast to pluripotent stem cells generated by somatic cell nuclear-transfer (SCNT) or ES cells derived from the inner cell mass (ICM) of the blastocyst, direct reprogramming provides a convenient and reliable means of generating pluripotent stem cells. iPS cells have already shown incredible potential for research and for therapeutic applications in regenerative medicine within just a few years of their discovery. In this review, current techniques of generating iPS cells and mechanisms of nuclear reprogramming are reviewed, and the potential for therapeutic applications is discussed. Antioxid. Redox Signal. 15, 1799–1820. PMID:21194386

  14. Early development and the emergence of individual differences in behavior among littermates of wild rabbit pups.

    Science.gov (United States)

    Rödel, Heiko G; Bautista, Amando; Roder, Manuel; Gilbert, Caroline; Hudson, Robyn

    2017-05-01

    The ontogeny of associated individual differences in behavior and physiology during early postnatal life, and in particular the emergence of such differences among litter siblings, has been hardly explored in mammals under natural conditions. We studied such within-litter differences in behavior in European rabbit pups Oryctolagus cuniculus prior to weaning, and whether and how these differences co-varied with other individual characteristics such as postnatal body temperature and early growth. The study was conducted under semi-natural conditions in a colony of rabbits of wild origin, where the young were born and developed in nursery burrows. We equipped two siblings per litter with interscapular skin temperature loggers on postnatal day 2 and recorded temperature profiles for 48h. Individual body (skin) temperatures of pups within litters were repeatable across time, indicating the existence of consistent individual differences. Such differences within litters were associated with relative differences in pre-weaning growth, revealing that relatively warmer pups showed a greater increase in body mass during the nest period. Between postnatal days 12 and 17, after the pups had reached a developmental stage of greater mobility, we carried out different behavioral tests: a handling-restraint test, an open field test and a jump-down test from a platform. Individual responses in the former two tests were associated, as those pups showing a quicker struggling response to restraint during handling also exhibited greater exploratory activity in the open field. This correlation across contexts suggests the existence of personality types in wild rabbits at an early developmental stage. Furthermore, pups' behavioral responses were strongly associated with their relative within-litter body mass at testing. Animals with a lower body mass compared to their siblings showed a relatively quicker struggle response to handling restraint and covered a relatively larger distance in

  15. Transfusion-associated circulatory overload in adult, medical emergency patients with perspectives on early warning practice

    DEFF Research Database (Denmark)

    Gosmann, Fanny; Nørgaard, Astrid; Rasmussen, Maj-Britt

    2018-01-01

    to the haemovigilance system. The clinical implications are discussed within the frame of the Early Warning Score. METHODS: We conducted a retrospective audit of electronic hospital medical records of patients receiving blood transfusion in a single medical emergency unit. Patients were admitted during a 6-month period......BACKGROUND: Transfusion-associated circulatory overload is characterised by acute respiratory distress, tachycardia, increased blood pressure, acute pulmonary oedema and/or evidence of positive fluid balance occurring within 6 hours after transfusion. Transfusion-associated circulatory overload...... and data on symptoms and vital signs were extracted from the records. RESULTS: Of 4,353 consecutively admitted patients, 156 patients were transfused with a total of 411 blood components. The audit identified five cases of transfusion-associated circulatory overload (incidence 3.2%) and four cases...

  16. Knowledge of Emergency Contraceptive Pills among Hungarian Women Presenting for Induced Abortion or Seeking Emergency Contraception.

    Science.gov (United States)

    Kozinszky, Z; Devosa, I; Fekete, Z; Szabó, D; Sikovanyecz, J; Pásztor, N; Keresztúri, A

    2016-09-01

    Aim: To compare the differences in contraceptive characteristics and the knowledge of emergency contraception (ECP) among women who used ECP after unprotected intercourse and those who sought an abortion. Methods: A questionnaire survey was conducted in a Hungarian university hospital among women for whom ECP was prescribed after unprotected intercourse (n = 940) as well as women who presented for the termination of pregnancy (n = 1592) between January 1, 2005 and November 20, 2006. Their knowledge of ECP and their experience with and attitudes toward ECP use were targeted. Results: The availability of ECP was well known (87.9 %), but it was still greatly underutilized: applied by only 13 of the 1592 women who resorted to abortion. Primarily, the ECP group consisted of those who experienced a condom failure significantly more often (odds ratio [OR] = 4.1), followed by those cases where ECP applications was a consequence of not using any kind of contraception (OR = 3.8). Fewer than one third (32 %) of the abortion seekers had previously used ECP, and only one fifth knew how to obtain it. Appropriate awareness of ECP was influenced by information obtained from health-care providers (adjusted odds ratio [AOR] = 3.93) or school education (AOR = 1.82). Conclusions: More thorough education is needed to provide a deeper knowledge of ECP use during contraceptive counseling for women seeking abortion, including those contraceptive mishaps where unintended pregnancy can be prevented by ECP.

  17. Brief report: Assessing youth well-being in global emergency settings: Early results from the Emergency Developmental Assets Profile.

    Science.gov (United States)

    Scales, Peter C; Roehlkepartain, Eugene C; Wallace, Teresa; Inselman, Ashley; Stephenson, Paul; Rodriguez, Michael

    2015-12-01

    The 13-item Emergency Developmental Assets Profile measures the well-being of children and youth in emergency settings such as refugee camps and armed conflict zones, assessing whether young people are experiencing adequate positive relationships and opportunities, and developing positive values, skills, and self-perceptions, despite being in crisis circumstances. The instrument was found to have acceptable and nearly identical internal consistency reliability in 22 administrations in non-emergency samples in 15 countries (.75), and in 4 samples of youth ages 10-18 (n = 1550) in the emergency settings (war refugees and typhoon victims, .74) that are the measure's focus, and evidence of convergent validity. Confirmatory Factor Analysis showed acceptable model fit among those youth in emergency settings. Measures of model fit showed that the Em-DAP has configural and metric invariance across all emergency contexts and scalar invariance across some. The Em-DAP is a promising brief cross-cultural tool for assessing the developmental quality of life as reported by samples of youth in a current humanitarian crisis situation. The results can help to inform international relief program decisions about services and activities to be provided for children, youth, and families in emergency settings. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  18. Development and Psychometric Evaluation of the Pre-hospital Medical Emergencies Early Warning Scale.

    Science.gov (United States)

    Ebrahimian, Abbasali; Masoumi, Gholamreza; Jamshidi-Orak, Roohangiz; Seyedin, Hesam

    2017-04-01

    The number of requests for emergency medical services (EMSs) has increased during the past decade. However, most of the transports are not essential. Therefore, it seems crucial to develop an instrument to help EMS staff accurately identify patients who need pre-hospital care and transportation. The aim of this study was to develop and evaluate the psychometric properties of the Pre-hospital Medical Emergencies Early Warning Scale (Pre-MEWS). This mixed-method study was conducted in two phases. In the first phase, a qualitative content analysis study was conducted to identify the predictors of medical patients' need for pre-hospital EMS and transportation. In the second phase, the face and the content validity as well as the internal consistency of the scale were evaluated. Finally, the items of the scale were scored and scoring system was presented. The final version of the scale contained 22 items and its total score ranged from 0 to 54. Pre-MEWS helps EMS staffs properly understand medical patients' conditions in pre-hospital environments and accurately identify their need for EMS and transportation.

  19. De-novo emergence of SINE retroposons during the early evolution of passerine birds.

    Science.gov (United States)

    Suh, Alexander; Bachg, Sandra; Donnellan, Stephen; Joseph, Leo; Brosius, Jürgen; Kriegs, Jan Ole; Schmitz, Jürgen

    2017-01-01

    Passeriformes ("perching birds" or passerines) make up more than half of all extant bird species. The genome of the zebra finch, a passerine model organism for vocal learning, was noted previously to contain thousands of short interspersed elements (SINEs), a group of retroposons that is abundant in mammalian genomes but considered largely inactive in avian genomes. Here we resolve the deep phylogenetic relationships of passerines using presence/absence patterns of SINEs. The resultant retroposon-based phylogeny provides a powerful and independent corroboration of previous sequence-based analyses. Notably, SINE activity began in the common ancestor of Eupasseres (passerines excluding the New Zealand wrens Acanthisittidae) and ceased before the rapid diversification of oscine passerines (suborder Passeri - songbirds). Furthermore, we find evidence for very recent SINE activity within suboscine passerines (suborder Tyranni), following the emergence of a SINE via acquisition of a different tRNA head as we suggest through template switching. We propose that the early evolution of passerines was unusual among birds in that it was accompanied by de-novo emergence and activity of SINEs. Their genomic and transcriptomic impact warrants further study in the light of the massive diversification of passerines.

  20. Pre-sowing Seed Treatments in Direct-seeded Early Rice: Consequences for Emergence, Seedling Growth and Associated Metabolic Events under Chilling Stress.

    Science.gov (United States)

    Wang, Weiqin; Chen, Qian; Hussain, Saddam; Mei, Junhao; Dong, Huanglin; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao

    2016-01-19

    Double direct-seeding for double rice cropping is a simplified, labor saving, and efficient cropping system to improve multiple-crop index and total rice production in central China. However, poor crop establishment of direct-seeded early rice due to chilling stress is the main obstacle to wide spread of this system. A series of experiments were conducted to unravel the effects of pre-sowing seed treatments on emergence, seedling growth and associated metabolic events of direct-seeded early rice under chilling stress. Two seed priming treatments and two seed coating treatments were used in all the experiments. A non-treated control treatment was also maintained for comparison. In both the field and growth chamber studies, seed priming with selenium or salicylic acid significantly enhanced the emergence and seedling growth of rice compared with non-treated control. Nevertheless, such positive effects were not apparent for seed coating treatments. Better emergence and vigorous seedling growth of rice after seed priming was associated with enhanced α-amylase activity, higher soluble sugars contents, and greater respiration rate in primed rice seedlings under chilling stress. Taking together, these findings may provide new avenues for understanding and advancing priming-induced chilling tolerance in direct-seeded early rice in double rice cropping system.

  1. Pre-sowing Seed Treatments in Direct-seeded Early Rice: Consequences for Emergence, Seedling Growth and Associated Metabolic Events under Chilling Stress

    Science.gov (United States)

    Wang, Weiqin; Chen, Qian; Hussain, Saddam; Mei, Junhao; Dong, Huanglin; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao

    2016-01-01

    Double direct-seeding for double rice cropping is a simplified, labor saving, and efficient cropping system to improve multiple-crop index and total rice production in central China. However, poor crop establishment of direct-seeded early rice due to chilling stress is the main obstacle to wide spread of this system. A series of experiments were conducted to unravel the effects of pre-sowing seed treatments on emergence, seedling growth and associated metabolic events of direct-seeded early rice under chilling stress. Two seed priming treatments and two seed coating treatments were used in all the experiments. A non-treated control treatment was also maintained for comparison. In both the field and growth chamber studies, seed priming with selenium or salicylic acid significantly enhanced the emergence and seedling growth of rice compared with non-treated control. Nevertheless, such positive effects were not apparent for seed coating treatments. Better emergence and vigorous seedling growth of rice after seed priming was associated with enhanced α-amylase activity, higher soluble sugars contents, and greater respiration rate in primed rice seedlings under chilling stress. Taking together, these findings may provide new avenues for understanding and advancing priming-induced chilling tolerance in direct-seeded early rice in double rice cropping system.

  2. A web based on-line radiation early warning system for emergency preparedness and response centre

    International Nuclear Information System (INIS)

    The topography of the Bhabha Atomic Research Centre, Trombay site, where all major components of nuclear fuel cycle activities are located is very complex in nature. The assessment of the radiological impact, if any, due to atmospheric releases from these facilities within BARC site is being carried out by using a Local Area Network (LAN) based Radiation Early Warning System and meteorological parameters. The upgraded system is aimed at providing data during normal operation of the various facilities at site and for providing early warning to decision makers in case of any onset of an emergency. It is carried out by acquiring both on-line and off-line data on releases from the plants, the environmental radiation dose rate at selected locations and other related parameters. The monitors placed at these selected locations including strategic point around the BARC site can also help in detecting any attempt of unauthorized trafficking of the radioactive sources. This paper explains different aspects of the system operating at BARC

  3. Accuracy of physical and ultrasonographic examinations by emergency physicians for the early diagnosis of intraabdominal haemorrhage in blunt abdominal trauma.

    Science.gov (United States)

    Soyuncu, S; Cete, Y; Bozan, H; Kartal, M; Akyol, A J

    2007-05-01

    To determine the accuracy of physical examination and ultrasonographic evaluation performed by emergency physicians in cases of blunt abdominal trauma for the early diagnosis of intraabdominal haemorrhage. In this clinical prospective study, trauma patients were evaluated with four-quadrant ultrasonography by emergency physicians after initial stabilisation and physical examination. Diagnoses based on demographic data, physical examination and emergency physician's ultrasonography were compared with the subsequent clinical course. A total of 442 patients participated in the study. The sensitivity and specificity of emergency physician's ultrasonographic examination to detect intraabdominal haemorrhage were 86 and 99%, respectively. Pre-test sensitivity and specificity of physical examination to detect intraabdominal haemorrhage were 39 and 90%, respectively. Physical examination was not a reliable method to detect intraabdominal haemorrhage in cases of blunt abdominal trauma. In contrast, abdominal ultrasonography performed by emergency physicians was a reliable diagnostic tool. Emergency physicians should be familiar with abdominal ultrasonographic examination, which should be routine in cases of blunt abdominal trauma.

  4. Near-field tsunami early warning and emergency planning in the Mediterranean Sea

    Directory of Open Access Journals (Sweden)

    Gerassimos A. Papadopoulos

    2013-04-01

    Full Text Available The new European project Near-field Tsunami Early Warning and Emergency Planning in the Mediterranean Sea (NEARTOWARN faces the need to develop operational tsunami early warning systems in near-field (local conditions where the travel time of the first tsunami wave is very short, that is less than 30 min, which is a typical case in the North East Atlantic and the Mediterranean Sea region but also elsewhere around the globe. The operational condition that should be fulfilled is that the time of tsunami detection, plus the time of warning transmitting, plus the time of evacuation should not exceed the travel time of the first tsunami wave from its source to the closest evacuation zone. To this goal the time to detect of the causative earthquake should be compressed at the very minimum. In this context the core of the proposed system is a network of seismic early warning devices, which activate and send alert in a few seconds after the generation of a near-field earthquake, when a seismic ground motion exceeding a prescribed threshold is detected. Then civil protection mobilizes to manage the earthquake crisis but also to detect and manage a possible tsunami through a geographical risk management system. For the tsunami detection the system is supported by tide-gauges of radar type, a database of presimulated tsunami scenarios, and a local tsunami decision matrix. The island of Rhodes in the eastern termination of the Hellenic Arc and Trench has been selected for a pilot and operational development of the local tsunami warning system given that the island is a highly popular tourist destination, historically it was hit by large tsunamigenic earthquakes and was recently the master test-site for the pan-European FP6 tsunami research project Tsunami Risk ANd Strategies For the European Region (TRANSFER.

  5. Emergency control of unstable behavior of nonlinear systems induced by fault

    Directory of Open Access Journals (Sweden)

    Mark A. Pinsky

    1998-01-01

    -functions significantly simplifying analysis and control of fault phenomena. The design of an mergency controller is based on the technique for computing fault-induced jumps of the system states, which is described in the paper. An emergency controller instantaneously returning states of a sample nonlinear system to its stability basin is designed.

  6. Multicountry survey of emergency and critical care medicine physicians' fluid resuscitation practices for adult patients with early septic shock

    DEFF Research Database (Denmark)

    McIntyre, Lauralyn; Rowe, Brian H; Walsh, Timothy S

    2016-01-01

    administered in early septic shock to inform the design of future septic shock fluid resuscitation trials. METHODS: Using a web-based survey tool, we invited critical care and emergency physicians in Canada, the UK, Scandinavia and Saudi Arabia to complete a self-administered electronic survey. RESULTS...... that a large randomised controlled trial comparing 5% albumin to a crystalloid fluid in early septic shock was important to conduct. CONCLUSIONS: Critical care and emergency physicians stated that they rapidly infuse volumes of 500-1000 mL of resuscitation fluid in early septic shock. Colloid use, specifically...... the use of albumin, was infrequently reported. Our survey identifies the need to conduct a trial on the efficacy of albumin and crystalloids on 90-day mortality in patients with early septic shock....

  7. Science for Humanitarian Emergencies and Resilience (SHEAR) scoping study: Annex 3 - Early warning system and risk assessment case studies

    OpenAIRE

    Brown, Sarah; Cornforth, Rosalind; Boyd, Emily; Standley, Sarah; Allen, Mary; Clement, Kalonga; Gonzalo, Alcade; Erwin, Garzona; Michelle, Slaney; Haseeb, Irfanullah; Maliha, Shahjajan

    2014-01-01

    This report provides case studies of Early Warning Systems (EWSs) and risk assessments encompassing three main hazard types: drought; flood and cyclone. The case studies are taken from ten countries across three continents (focusing on Africa, South Asia and the Caribbean).\\ud The case studies have been developed to assist the UK Department for International Development (DFID) to prioritise areas for Early Warning System (EWS) related research under their ‘Science for Humanitarian Emergencies...

  8. Recurrent sigmoid volvulus - early resection may obviate later emergency surgery and reduce morbidity and mortality.

    LENUS (Irish Health Repository)

    Larkin, J O

    2012-01-31

    INTRODUCTION: Acute sigmoid volvulus is a well recognised cause of acute large bowel obstruction. PATIENTS AND METHODS: We reviewed our unit\\'s experience with non-operative and operative management of this condition. A total of 27 patients were treated for acute sigmoid volvulus between 1996 and 2006. In total, there were 62 separate hospital admissions. RESULTS: Eleven patients were managed with colonoscopic decompression alone. The overall mortality rate for non-operative management was 36.4% (4 of 11 patients). Fifteen patients had operative management (five semi-elective following decompression, 10 emergency). There was no mortality in the semi-elective cohort and one in the emergency surgery group. The overall mortality for surgery was 6% (1 of 15). Five of the seven patients managed with colonoscopic decompression alone who survived were subsequently re-admitted with sigmoid volvulus (a 71.4% recurrence rate). The six deaths in our overall series each occurred in patients with established gangrene of the bowel. With early surgical intervention before the onset of gangrene, however, good outcomes may be achieved, even in patients apparently unsuitable for elective surgery. Eight of the 15 operatively managed patients were considered to be ASA (American Society of Anesthesiologists) grade 4. There was no postoperative mortality in this group. CONCLUSIONS: Given the high rate of recurrence of sigmoid volvulus after initial successful non-operative management and the attendant risks of mortality from gangrenous bowel developing with a subsequent volvulus, it is our contention that all patients should be considered for definitive surgery after initial colonoscopic decompression, irrespective of the ASA score.

  9. The emergence of semantic categorization in early visual processing: ERP indices of animal vs. artifact recognition

    Directory of Open Access Journals (Sweden)

    Del Zotto Marzia

    2007-04-01

    Full Text Available Abstract Background Neuroimaging and neuropsychological literature show functional dissociations in brain activity during processing of stimuli belonging to different semantic categories (e.g., animals, tools, faces, places, but little information is available about the time course of object perceptual categorization. The aim of the study was to provide information about the timing of processing stimuli from different semantic domains, without using verbal or naming paradigms, in order to observe the emergence of non-linguistic conceptual knowledge in the ventral stream visual pathway. Event related potentials (ERPs were recorded in 18 healthy right-handed individuals as they performed a perceptual categorization task on 672 pairs of images of animals and man-made objects (i.e., artifacts. Results Behavioral responses to animal stimuli were ~50 ms faster and more accurate than those to artifacts. At early processing stages (120–180 ms the right occipital-temporal cortex was more activated in response to animals than to artifacts as indexed by posterior N1 response, while frontal/central N1 (130–160 showed the opposite pattern. In the next processing stage (200–260 the response was stronger to artifacts and usable items at anterior temporal sites. The P300 component was smaller, and the central/parietal N400 component was larger to artifacts than to animals. Conclusion The effect of animal and artifact categorization emerged at ~150 ms over the right occipital-temporal area as a stronger response of the ventral stream to animate, homomorphic, entities with faces and legs. The larger frontal/central N1 and the subsequent temporal activation for inanimate objects might reflect the prevalence of a functional rather than perceptual representation of manipulable tools compared to animals. Late ERP effects might reflect semantic integration and cognitive updating processes. Overall, the data are compatible with a modality-specific semantic memory

  10. Text mining approach to predict hospital admissions using early medical records from the emergency department.

    Science.gov (United States)

    Lucini, Filipe R; S Fogliatto, Flavio; C da Silveira, Giovani J; L Neyeloff, Jeruza; Anzanello, Michel J; de S Kuchenbecker, Ricardo; D Schaan, Beatriz

    2017-04-01

    Emergency department (ED) overcrowding is a serious issue for hospitals. Early information on short-term inward bed demand from patients receiving care at the ED may reduce the overcrowding problem, and optimize the use of hospital resources. In this study, we use text mining methods to process data from early ED patient records using the SOAP framework, and predict future hospitalizations and discharges. We try different approaches for pre-processing of text records and to predict hospitalization. Sets-of-words are obtained via binary representation, term frequency, and term frequency-inverse document frequency. Unigrams, bigrams and trigrams are tested for feature formation. Feature selection is based on χ 2 and F-score metrics. In the prediction module, eight text mining methods are tested: Decision Tree, Random Forest, Extremely Randomized Tree, AdaBoost, Logistic Regression, Multinomial Naïve Bayes, Support Vector Machine (Kernel linear) and Nu-Support Vector Machine (Kernel linear). Prediction performance is evaluated by F1-scores. Precision and Recall values are also informed for all text mining methods tested. Nu-Support Vector Machine was the text mining method with the best overall performance. Its average F1-score in predicting hospitalization was 77.70%, with a standard deviation (SD) of 0.66%. The method could be used to manage daily routines in EDs such as capacity planning and resource allocation. Text mining could provide valuable information and facilitate decision-making by inward bed management teams. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  12. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  13. A quality improvement project to improve early sepsis care in the emergency department.

    Science.gov (United States)

    Gatewood, Medley O'Keefe; Wemple, Matthew; Greco, Sheryl; Kritek, Patricia A; Durvasula, Raghu

    2015-12-01

    Sepsis causes substantial morbidity and mortality in hospitalised patients. Although many studies describe the use of protocols in the management of patients with severe sepsis and septic shock, few have addressed emergency department (ED) screening and management for patients initially presenting with uncomplicated sepsis (ie, patients without organ failure or hypotension). A quality improvement task force at a large, quaternary care referral hospital sought to develop a protocol focusing on early identification of patients with uncomplicated sepsis, in addition to severe sepsis and septic shock. The three-tiered intervention consisted of (1) a nurse-driven screening tool and management protocol to identify and initiate early treatment of patients with sepsis, (2) a computer-assisted screening algorithm that generated a 'Sepsis Alert' pop-up screen in the electronic medical record for treating clinical healthcare providers and (3) automated suggested sepsis-specific order sets for initial workup and resuscitation, antibiotic selection and goal-directed therapy. A before and after retrospective cohort study was undertaken to determine the intervention's impact on compliance with recommended sepsis management, including serum lactate measured in the ED, 2 L of intravenous fluid administered within 2 h of triage, antibiotics administered within 3 h of triage and blood cultures drawn before antibiotic administration. Mortality rates for patients in the ED with a sepsis-designated ICD-9 code present on admission were also analysed. Overall bundle compliance increased by 154%, from 28% at baseline to 71% in the last quarter of the study (p<0.001). Bundle, antibiotic and intravenous fluid compliance all increased significantly after launch of the sepsis initiative (eg, bundle and intravenous fluid compliance increased by 74% and 54%, respectively; p<0.001). Bundle and antibiotic compliance both showed further significant increases after implementation of suggested

  14. Early medieval stone-lined graves in Southern Germany: analysis of an emerging noble class.

    Science.gov (United States)

    Rott, Andreas; Turner, Nils; Scholz, Ulrike; von Heyking, Kristin; Immler, Franziska; Peters, Joris; Haberstroh, Jochen; Harbeck, Michaela

    2017-04-01

    Stone-lined graves, which first appear in Bavarian territory during the 7 th century AD, are assumed to be tombs of emerging nobility. While previous research on stone-lined grave goods supports their status as elite burials, an important factor defining nobility-kinship-has not been examined so far. Morphological analysis of the commingled skeletal remains of 21 individuals from three archaeological sites was carried out. Radiocarbon dating was conducted on these individuals to gain information on usage intervals of these graves. To test whether stone-lined graves can be considered family graves, analyses of mitochondrial HVR I, Y-chromosomal and autosomal STRs were carried out. Morphological examination revealed a surplus of males buried in stone-lined graves and radiocarbon dating points to usage of the tombs for several generations. According to aDNA analysis, kinship can be assumed both between and within stone-lined graves. Taken together, these results hint at burials of family members with high social status being inhumed at the same site, in some cases even the same grave, for several generations. They also suggest, for the first time, that an early medieval linear cemetery was structured according to biological kinship. © 2017 Wiley Periodicals, Inc.

  15. Theory of mind in emerging reading comprehension: A longitudinal study of early indirect and direct effects.

    Science.gov (United States)

    Atkinson, Lynette; Slade, Lance; Powell, Daisy; Levy, Joseph P

    2017-12-01

    The relation between children's theory of mind (ToM) and emerging reading comprehension was investigated in a longitudinal study over 2.5years. A total of 80 children were tested for ToM, decoding, language skills, and executive function (EF) at Time 1 (mean age=3;10 [years;months]). At Time 2 (mean age=6;03), children's word reading efficiency, language skills, and reading comprehension were measured. Mediation analysis showed that ToM at Time 1, when children were around 4years old, indirectly predicted Time 2 reading comprehension, when children were 6years old, via language ability after controlling for age, nonverbal ability, decoding, EF, and earlier language ability. Importantly, ToM at 4years also directly predicted reading comprehension 2.5years later at 6years. This is the first longitudinal study to show a direct contribution of ToM to reading comprehension in typical development. Findings are discussed in terms of the simple view of reading (SVR); ToM not only supports reading comprehension indirectly by facilitating language but also contributes to it directly over and above the SVR. The potential role of metacognition is considered when accounting for the direct contribution of early ToM to later reading comprehension. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Facilitative and Inhibitory Effect of Litter on Seedling Emergence and Early Growth of Six Herbaceous Species in an Early Successional Old Field Ecosystem

    Science.gov (United States)

    Li, Qiang; Yu, Pujia; Chen, Xiaoying; Li, Guangdi; Zhou, Daowei; Zheng, Wei

    2014-01-01

    In the current study, a field experiment was conducted to examine effects of litter on seedling emergence and early growth of four dominant weed species from the early successional stages of old field ecosystem and two perennial grassland species in late successional stages. Our results showed that increased litter cover decreased soil temperature and temperature variability over time and improved soil moisture status. Surface soil electrical conductivity increased as litter increased. The increased litter delayed seedling emergence time and rate. The emergence percentage of seedlings and establishment success rate firstly increased then decreased as litter cover increased. When litter biomass was below 600 g m−2, litter increased seedlings emergence and establishment success in all species. With litter increasing, the basal diameter of seedling decreased, but seedling height increased. Increasing amounts of litter tended to increase seedling dry weight and stem leaf ratio. Different species responded differently to the increase of litter. Puccinellia tenuiflora and Chloris virgata will acquire more emergence benefits under high litter amount. It is predicted that Chloris virgata will dominate further in this natural succession old field ecosystem with litter accumulation. Artificial P. tenuiflora seeds addition may be required to accelerate old field succession toward matured grassland. PMID:25110722

  17. The New FARM Program: A Model for Supporting Diverse Emerging Farmers and Early-Career Extension Professionals

    Science.gov (United States)

    Sirrine, J. R.; Eschbach, Cheryl L.; Lizotte, Erin; Rothwell, N. L.

    2016-01-01

    As early-career Extension educators challenged by societal, structural, agricultural, and fiscal trends, we designed a multiyear educational program to support the diverse needs of emerging specialty crop producers in northwest Michigan. This article presents outcomes of that program. We explore how Extension professionals can develop impactful…

  18. The Co-Emergence of Cognition, Language, and Speech Motor Control in Early Development: A Longitudinal Correlation Study

    Science.gov (United States)

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.

    2011-01-01

    Although the development of spoken language is dependent on the emergence of cognitive, language, and speech motor skills, knowledge about how these domains interact during the early stages of communication development is currently limited. This exploratory investigation examines the strength of associations between longitudinal changes in…

  19. Biomarkers for the early detection of cancer treatment induced cardiotoxicity

    NARCIS (Netherlands)

    Bulten, Ben

    2016-01-01

    In this thesis, the role of several imaging and nonimaging markers for the detection of anthracycline-induced and trastuzumab-induced cardiotoxicity (respectively AIC and TIC) is evaluated. Especially, the pathophysiology of these processes and the interrelationship of the various markers are

  20. Early micronutrient supplementation protects against early stress-induced cognitive impairments

    NARCIS (Netherlands)

    Naninck, Eva F. G.; Oosterink, J. Efraim; Yam, Kit-Yi; de Vries, Lennart P.; Schierbeek, Henk; van Goudoever, Johannes B.; Verkaik-Schakel, Rikst Nynke; Plantinga, Josee; Plosch, Torsten; Lucassen, Paul J.; Korosi, Aniko

    Early-life stress (ES) impairs cognition later in life. Because ES prevention is problematic, intervention is needed, yet the mechanisms that underlie ES remain largely unknown. So far, the role of early nutrition in brain programming has been largely ignored. Here, we demonstrate that essential

  1. Development of a decision support system for off-site emergency management in the early phase of a nuclear accident

    International Nuclear Information System (INIS)

    Datta, D.; Sharma, R.M.

    2002-01-01

    Full text: Experience gained after the Chernobyl accident clearly demonstrated the importance of improving administrative, organizational and technical emergency management arrangements in India. The more important areas where technical improvements were needed were early warning monitoring, communication networks for the rapid and reliable exchange of radiological and other information and decision support systems for off-site emergency management. A PC based artificial intelligent software has been developed to have a decision support system that can easily implement to manage off-site nuclear emergency and subsequently analyze the off-site consequences of the nuclear accident. A decision support tool, STEPS (source term estimate based on plant status), that provides desired input to the present software was developed. The tool STEPS facilitates meta knowledge of the system. The paper describes the details of the design of the software, functions of various modules, tuning of respective knowledge base and overall its scope in real sense in nuclear emergency preparedness and response

  2. Jogging-induced spontaneous peri-renal hemorrhage: a rare urologic emergency.

    Science.gov (United States)

    Jabbour, Michel; Dalati, Mohamad-Fadi

    2014-01-01

    Spontaneous peri-renal hemorrhage (SPH), also known as Wünderlich's syndrome, is an uncommon and rare urologic emergency, which could become life-threatening, requiring immediate diagnosis and management. The diagnosis can be challenging, even with new imaging modalities, and management can vary from conservative approach, to surgical intervention. We present a case of jogging-induced SPH diagnosed using CT scan that was managed conservatively, with follow-up for up to five years using CT imaging studies.

  3. Dose assessment for emergency workers in early phase of Fukushima Daiichi nuclear power plant accident

    International Nuclear Information System (INIS)

    Sadeghi, Nahid; Ahangari, Rohollah; Kasesaz, Yaser; Noori-kalkhoran, O.

    2017-01-01

    In the case of Fukushima Daiichi nuclear power plant (FNP) accident, the radioactive material was released from reactor units 1-3 and transported to short and long distances due to the atmospheric pathways-motions. Power sources for monitoring posts were lost due to earthquake and tsunami. Based on air dose rates and other data measured by monitoring cars, the amount of radioactive material released to the atmosphere from the power station was obtained. The atmospheric dispersion and the transport model used in the RASCAL code, estimate the radionuclide concentrations downwind, both in the air and on the ground due to deposition. The calculated concentrations are then used to estimate the projected doses for workers in vicinity of the accident area in the first minutes of accident time. For dose modeling, we assumed that each worker was 15 min in vicinity of FNP in accident situation, once without and once with protective clothes or respirator. According to Tokyo Electric Power Company (TEPCO) report six workers had received doses over 250 mSv (309 to 678 mSv) apparently due to inhaling Iodine-131 fume. In this paper the calculated dose results using RASCAL code shows that, if emergency workers who work in early phase of accident had not used protective equipment, for 15 min, inhalation doses from iodine in their thyroid gland up to 12 March afternoon would have been 520 mSv. A comparison between calculation results and TEPCO report shows that dose calculated virtually is nearly equal to TEPCO measurement results.

  4. Anything but Shadowing! Early Clinical Reasoning in Emergency Department Improves Clinical Skills.

    Science.gov (United States)

    Royan, Regina; Wu, Christine; Theyyunni, Nik; Montas, Sacha; Cranford, James A; House, Joseph B; Lukela, Michael P; Santen, Sally A

    2018-01-01

    Transitioning from the pre-clinical environment to clerkships poses a challenge to students and educators alike. Students along with faculty developed the Clinical Reasoning Elective (CRE) to provide pre-clinical students exposure to patients in the emergency department and the opportunity to build illness scripts and practice clinical skills with longitudinal mentorship in a low-stakes environment before entering clerkships. It is a voluntary program. Each year, the CRE has received overwhelming positive feedback from students. The objective of this study is to determine if the CRE improved students' clinical skills and reported comfort in their skills. We examined the relationships between students' self-reported participation in the CRE and their individual scores on a comprehensive clinical assessment (CCA) at the end of the pre-clerkship period. A total of 178 students took the CCA exam in 2016. Of these, 113 participated in the CRE and 65 did not. Seven students who participated in CRE did not complete the exit survey and were omitted from analysis. We performed regression analysis and dichotomous (participants/nonparticipants) comparisons of means with t-tests. Survey of student reactions was collected. Participants completed an average of 10 sessions over the course of the program (range=1-20). Involvement in the CRE was associated with significantly increased scores on Abdominal History; Pulmonary Physical Exam; Overall History-Taking; Overall Communication; and Overall Physical Exam (p<0.05). Nearly all students (97%) reported that the program offered opportunities to enhance clinical skills, increased their comfort with patients, and better prepared them for their clinical years. There were measurable improvements in clinical skills performance for students who participated in CRE. As many schools seek to incorporate early clinical exposure to their curricula, this program provides a successful framework to provide meaningful clinical exposure to real

  5. Anything but Shadowing! Early Clinical Reasoning in Emergency Department Improves Clinical Skills

    Directory of Open Access Journals (Sweden)

    Regina Royan

    2017-12-01

    Full Text Available Introduction Transitioning from the pre-clinical environment to clerkships poses a challenge to students and educators alike. Students along with faculty developed the Clinical Reasoning Elective (CRE to provide pre-clinical students exposure to patients in the emergency department and the opportunity to build illness scripts and practice clinical skills with longitudinal mentorship in a low-stakes environment before entering clerkships. It is a voluntary program. Each year, the CRE has received overwhelming positive feedback from students. The objective of this study is to determine if the CRE improved students’ clinical skills and reported comfort in their skills. Methods We examined the relationships between students’ self-reported participation in the CRE and their individual scores on a comprehensive clinical assessment (CCA at the end of the pre-clerkship period. A total of 178 students took the CCA exam in 2016. Of these, 113 participated in the CRE and 65 did not. Seven students who participated in CRE did not complete the exit survey and were omitted from analysis. We performed regression analysis and dichotomous (participants/nonparticipants comparisons of means with t-tests. Survey of student reactions was collected. Results Participants completed an average of 10 sessions over the course of the program (range=1–20. Involvement in the CRE was associated with significantly increased scores on Abdominal History; Pulmonary Physical Exam; Overall History-Taking; Overall Communication; and Overall Physical Exam (p<0.05. Nearly all students (97% reported that the program offered opportunities to enhance clinical skills, increased their comfort with patients, and better prepared them for their clinical years. Conclusion There were measurable improvements in clinical skills performance for students who participated in CRE. As many schools seek to incorporate early clinical exposure to their curricula, this program provides a successful

  6. Dose assessment for emergency workers in early phase of Fukushima Daiichi nuclear power plant accident

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi, Nahid; Ahangari, Rohollah; Kasesaz, Yaser; Noori-kalkhoran, O. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of). Reactor Research School

    2017-11-15

    In the case of Fukushima Daiichi nuclear power plant (FNP) accident, the radioactive material was released from reactor units 1-3 and transported to short and long distances due to the atmospheric pathways-motions. Power sources for monitoring posts were lost due to earthquake and tsunami. Based on air dose rates and other data measured by monitoring cars, the amount of radioactive material released to the atmosphere from the power station was obtained. The atmospheric dispersion and the transport model used in the RASCAL code, estimate the radionuclide concentrations downwind, both in the air and on the ground due to deposition. The calculated concentrations are then used to estimate the projected doses for workers in vicinity of the accident area in the first minutes of accident time. For dose modeling, we assumed that each worker was 15 min in vicinity of FNP in accident situation, once without and once with protective clothes or respirator. According to Tokyo Electric Power Company (TEPCO) report six workers had received doses over 250 mSv (309 to 678 mSv) apparently due to inhaling Iodine-131 fume. In this paper the calculated dose results using RASCAL code shows that, if emergency workers who work in early phase of accident had not used protective equipment, for 15 min, inhalation doses from iodine in their thyroid gland up to 12 March afternoon would have been 520 mSv. A comparison between calculation results and TEPCO report shows that dose calculated virtually is nearly equal to TEPCO measurement results.

  7. Investigation of early plasma evolution induced by ultrashort laser pulses.

    Science.gov (United States)

    Hu, Wenqian; Shin, Yung C; King, Galen B

    2012-07-02

    Early plasma is generated owing to high intensity laser irradiation of target and the subsequent target material ionization. Its dynamics plays a significant role in laser-material interaction, especially in the air environment(1-11). Early plasma evolution has been captured through pump-probe shadowgraphy(1-3) and interferometry(1,4-7). However, the studied time frames and applied laser parameter ranges are limited. For example, direct examinations of plasma front locations and electron number densities within a delay time of 100 picosecond (ps) with respect to the laser pulse peak are still very few, especially for the ultrashort pulse of a duration around 100 femtosecond (fs) and a low power density around 10(14) W/cm(2). Early plasma generated under these conditions has only been captured recently with high temporal and spatial resolutions(12). The detailed setup strategy and procedures of this high precision measurement will be illustrated in this paper. The rationale of the measurement is optical pump-probe shadowgraphy: one ultrashort laser pulse is split to a pump pulse and a probe pulse, while the delay time between them can be adjusted by changing their beam path lengths. The pump pulse ablates the target and generates the early plasma, and the probe pulse propagates through the plasma region and detects the non-uniformity of electron number density. In addition, animations are generated using the calculated results from the simulation model of Ref. (12) to illustrate the plasma formation and evolution with a very high resolution (0.04 ~ 1 ps). Both the experimental method and the simulation method can be applied to a broad range of time frames and laser parameters. These methods can be used to examine the early plasma generated not only from metals, but also from semiconductors and insulators.

  8. Anthracycline-induced cardiotoxicity, a pathophysiology based approach for early detection and protective strategies

    NARCIS (Netherlands)

    Broeyer, Frederik Jan Ferdinand

    2012-01-01

    In this thesis the development of a pathophysiology-based method for the early evaluation of anthracycline-induced cardiotoxicity was described. We evaluated a comprehensive array of biomarkers, representing several aspects of anthracycline-induced cardiotoxicity, including cardiac injury and

  9. Management of drug-induced hyperbilirubinaemia in early pregnancy

    African Journals Online (AJOL)

    We report on two pregnant women who developed severe drug-induced hepatic failure and hyperbilirubinaemia during the period of fetal organogenesis. ... of the drug suspected to be causing the condition is the optimal management, immediately decreasing the maternal bilirubin level and improving the perinatal ...

  10. Paucity of Intact Non-Induced Provirus with Early, Long-Term Antiretroviral Therapy of Perinatal HIV Infection.

    Science.gov (United States)

    Rainwater-Lovett, Kaitlin; Ziemniak, Carrie; Watson, Douglas; Luzuriaga, Katherine; Siberry, George; Petru, Ann; Chen, YaHui; Uprety, Priyanka; McManus, Margaret; Ho, Ya-Chi; Lamers, Susanna L; Persaud, Deborah

    2017-01-01

    The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART) and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA) that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG) suggests the QVOA significantly underestimates (by 62-fold) latent reservoir size in chronically-infected adults. Whether formation and persistence of Intact, NIPG is thwarted by early ART initiation and long-term virologic suppression in perinatal infection is unclear. Here, we show that the latent reservoir in 11 early treated, long-term suppressed perinatally infected children and adolescents was not inducible by QVOA and dominated by defective, NIPG. Single genome analysis of 164 NIPG from 232 million cultured resting CD4+ T cells revealed no replication-intact, near-full length sequences. Forty-three (26%) NIPG contained APOBEC3G-mediated hypermutation, 115 (70%) NIPG contained large internal deletions, one NIPG contained nonsense mutations and indels, and 5 (3%) NIPG were assigned as "Not Evaluable" due to multiple failed sequencing attempts that precluded further classification. The lack of replication competent inducible provirus and intact NIPG in this cohort indicate early, long-term ART of perinatal infection leads to marked diminution of replication-competent HIV-1 reservoirs, creating a favorable state towards interventions aimed at virologic remission.

  11. Paucity of Intact Non-Induced Provirus with Early, Long-Term Antiretroviral Therapy of Perinatal HIV Infection.

    Directory of Open Access Journals (Sweden)

    Kaitlin Rainwater-Lovett

    Full Text Available The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG suggests the QVOA significantly underestimates (by 62-fold latent reservoir size in chronically-infected adults. Whether formation and persistence of Intact, NIPG is thwarted by early ART initiation and long-term virologic suppression in perinatal infection is unclear. Here, we show that the latent reservoir in 11 early treated, long-term suppressed perinatally infected children and adolescents was not inducible by QVOA and dominated by defective, NIPG. Single genome analysis of 164 NIPG from 232 million cultured resting CD4+ T cells revealed no replication-intact, near-full length sequences. Forty-three (26% NIPG contained APOBEC3G-mediated hypermutation, 115 (70% NIPG contained large internal deletions, one NIPG contained nonsense mutations and indels, and 5 (3% NIPG were assigned as "Not Evaluable" due to multiple failed sequencing attempts that precluded further classification. The lack of replication competent inducible provirus and intact NIPG in this cohort indicate early, long-term ART of perinatal infection leads to marked diminution of replication-competent HIV-1 reservoirs, creating a favorable state towards interventions aimed at virologic remission.

  12. Gamma-ray-induced bold seeded early maturing groundnut selections

    International Nuclear Information System (INIS)

    Manoharan, V.; Thangavelu, S.

    1990-01-01

    Full text: ''Chico'' is an early maturing (85-90 days) erect groundnut (Arachis hypogaea L.) genotype utilised in groundnut improvement to incorporate earliness in high yielding varieties. Though it has high shelling out-turn, its yield potential is low since it has small seeds. Mutation breeding was started with the objective of improving the seed size. In a preliminary experiment, dry seeds were treated with 20, 30, 40 or 50 kR of gamma rays. The M 1 generation was grown during the post rainy season of 1988-1989. The M 2 generation was planted as individual plant progeny rows during the rainy season of 1989. 105 progeny rows were studied, the total number of M 2 plants being 1,730. All the M 2 plants were harvested 90 days after sowing. Seven mutants with bold seed size were obtained. The mutants had 100 kernel weight ranging from 22.2 to 40.4 g compared to 21.1 g of control. The study is in progress. (author)

  13. A rat model of early stage osteonecrosis induced by glucocorticoids

    Directory of Open Access Journals (Sweden)

    Kerachian Mohammad

    2011-12-01

    Full Text Available Abstract Background Glucocorticoid (GC-induced osteonecrosis (ON is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario. Methods To determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis. Prednisone pellets (dosage of 1.82-2.56 mg/kg/day were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate. Results The greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes. Conclusions We postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.

  14. Food Allergy Emergencies in Children – To what extent are Early Years Services Prepared? A cross-sectional survey

    LENUS (Irish Health Repository)

    MacGiobuin, S

    2017-08-01

    Food allergies are common in preschool children. This study’s aims are to establish prevalence, to clarify management practices, levels of preparedness and the perceived role of General Practitioners amongst Early Years Services providers. This study is an anonymous, quantitative, cross sectional study. An online questionnaire was distributed to 282 Early Years Service providers. Data were analysed using SPSS. Response rate was 35% (n=98). Prevalence of food allergy was 3% (n=119). Allergic reactions to food had occurred on site in 16% (n=15). Written emergency action plans were available in 47% of facilities (n=46). Medications were not kept on site in 63% (n=62) of facilities. General practitioners were felt to have an important role in the management of food allergies by 76% of respondents (n=61). This study identifies significant areas for improvement in the management of food allergic child in Early Years Services

  15. Emerging roles of epigenetic mechanisms in the enduring effects of early-life stress and experience on learning and memory.

    Science.gov (United States)

    McClelland, Shawn; Korosi, Aniko; Cope, Jessica; Ivy, Autumn; Baram, Tallie Z

    2011-07-01

    Epigenetic mechanisms are involved in programming gene expression throughout development. In addition, they are key contributors to the processes by which early-life experience fine-tunes the expression levels of key neuronal genes, governing learning and memory throughout life. Here we describe the long-lasting, bi-directional effects of early-life experience on learning and memory. We discuss how enriched postnatal experience enduringly augments spatial learning, and how chronic early-life stress results in persistent and progressive deficits in the structure and function of hippocampal neurons. The existing and emerging roles of epigenetic mechanisms in these fundamental neuroplasticity phenomena are illustrated. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. On the early emergence of reverse transcription: theoretical basis and experimental evidence

    Science.gov (United States)

    Lazcano, A.; Valverde, V.; Hernandez, G.; Gariglio, P.; Fox, G. E.; Oro, J.

    1992-01-01

    Reverse transcriptase (RT) was first discovered as an essential catalyst in the biological cycle of retroviruses. However, in the past years evidence has accumulated showing that RTs are involved in a surprisingly large number of RNA-mediated transpositional events that include both viral and nonviral genetic entities. Although it is probable that some RT-bearing genetic elements like the different types of AIDS viruses and the mammalian LINE family have arisen in recent geological times, the possibility that reverse transcription first took place in the early Archean is supported by (1) the hypothesis that RNA preceded DNA as cellular genetic material; (2) the existence of homologous regions of the subunit tau of the E. coli DNA polymerase III with the simian immunodeficiency virus RT, the hepatitis B virus RT, and the beta' subunit of the E. coli RNA polymerase (McHenry et al. 1988); (3) the presence of several conserved motifs, including a 14-amino-acid segment that consists of an Asp-Asp pair flanked by hydrophobic amino acids, which are found in all RTs and in most cellular and viral RNA polymerases. However, whether extant RTs descend from the primitive polymerase involved in the RNA-to-DNA transition remains unproven. Substrate specificity of the AMV and HIV-1 RTs can be modified in the presence of Mn2+, a cation which allows them to add ribonucleotides to an oligo (dG) primer in a template-dependent reaction. This change in specificity is comparable to that observed under similar conditions in other nucleic acid polymerases. This experimentally induced change in RT substrate specificity may explain previous observations on the misincorporation of ribonucleotides by the Maloney murine sarcoma virus RT in the minus and plus DNA of this retrovirus (Chen and Temin 1980). Our results also suggest that HIV-infected macrophages and T-cell cells may contain mixed polynucleotides containing both ribo- and deoxyribonucleotides. The evolutionary significance of these

  17. The Emergence of Solitude as a Constructive Domain of Experience in Early Adolescence.

    Science.gov (United States)

    Larson, Reed W.

    1997-01-01

    Studied developmental changes in the experience of solitude between late childhood and early adolescence. Fifth through ninth graders (N=483) provided experience-sampling reports on their companionship and subjective states at random times over a week. Found that in early adolescence solitude comes to have a more constructive role in daily life as…

  18. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Tzu-Yi; Hong, Chwan-Yang [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China); Sasado, Takao [Laboratory of Bioresources, National Institute for Basic Biology, Okazaki (Japan); Kashiwada, Shosaku [Research Center for Life and Environmental Sciences, Department of Life Sciences, the Toyo University, Gunma (Japan); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan (China)

    2016-01-15

    Highlights: • Propiconazole initiates ROS-induced oxidative stress and damage in medaka fish. • Early life exposure to propiconazole increases incidence of hepatocarcionogensis in p53{sup −/−} medaka. • Oxidative stress and CYP induction involved in p53 regulation are key events in propiconazole-induced hepatotumorigenesis. • Propiconazole-induced toxic response in medaka is compatible with that in rodents. - Abstract: Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53{sup −/−} mutant of medaka fish (Oryzias latipes) to propiconazole (2.5–250 μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53{sup −/−} mutant medaka with early life exposure to propiconazole showed increased incidence of

  19. Ca2+-Induced Mitochondrial ROS Regulate the Early Embryonic Cell Cycle.

    Science.gov (United States)

    Han, Yue; Ishibashi, Shoko; Iglesias-Gonzalez, Javier; Chen, Yaoyao; Love, Nick R; Amaya, Enrique

    2018-01-02

    While it is appreciated that reactive oxygen species (ROS) can act as second messengers in both homeostastic and stress response signaling pathways, potential roles for ROS during early vertebrate development have remained largely unexplored. Here, we show that fertilization in Xenopus embryos triggers a rapid increase in ROS levels, which oscillate with each cell division. Furthermore, we show that the fertilization-induced Ca 2+ wave is necessary and sufficient to induce ROS production in activated or fertilized eggs. Using chemical inhibitors, we identified mitochondria as the major source of fertilization-induced ROS production. Inhibition of mitochondrial ROS production in early embryos results in cell-cycle arrest, in part, via ROS-dependent regulation of Cdc25C activity. This study reveals a role for oscillating ROS levels in early cell cycle regulation in Xenopus embryos. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Effective early warning systems for new and emerging health technologies: developing an evaluation framework and an assessment of current systems.

    Science.gov (United States)

    Murphy, Kieran; Packer, Claire; Stevens, Andrew; Simpson, Sue

    2007-01-01

    The aim of this study was to define an effective early warning system, to identify and rank the characteristics of an effective early warning system for emerging health technologies, and to evaluate current early warning systems against these characteristics. An iterative Delphi-type process with the thirteen members of the International Information Network on New and Changing Health Technologies (EuroScan). We synthesized key characteristics that network members had graded. Members were then asked whether these characteristics were present or fulfilled in their system. The definition of an effective early warning system developed was the following: a system that identifies innovations in the field of health technology likely to have a significant impact; and disseminates information relevant to the needs of the customer which is timely, so as to enable appropriate decision making (such as resource allocation), facilitate appropriate adoption, and identify further research requirements. Five primary and eleven secondary components of effective early warning systems were identified. The five primary characteristics concerned relevance, independence, resourcing, a clear pathway for the outputs to reach decision makers, and defined customers. Although the primary characteristics were present or fulfilled to some extent in the majority of evaluated early warning systems, there was considerable variability in the presence of the secondary characteristics in the evaluated systems. Our study provides a definition for an effective early warning system and a shared understanding of the important characteristics and components of such systems. This work should provide guidance to those setting up new early warning systems as well as for those managing and reviewing current systems.

  1. Laying a Firm Foundation: Embedding Evidence-Based Emergent Literacy Practices Into Early Intervention and Preschool Environments.

    Science.gov (United States)

    Terrell, Pamela; Watson, Maggie

    2018-04-05

    As part of this clinical forum on curriculum-based intervention, the goal of this tutorial is to share research about the importance of language and literacy foundations in natural environments during emergent literacy skill development, from infancy through preschool. Following an overview of intervention models in schools by Powell (2018), best practices at home, in child care, and in preschool settings are discussed. Speech-language pathologists in these settings will be provided a toolbox of best emergent literacy practices. A review of published literature in speech-language pathology, early intervention, early childhood education, and literacy was completed. Subsequently, an overview of the impact of early home and preschool literacy experiences are described. Research-based implementation of best practice is supported with examples of shared book reading and child-led literacy embedded in play within the coaching model of early intervention. Finally, various aspects of emergent literacy skill development in the preschool years are discussed. These include phonemic awareness, print/alphabet awareness, oral language skills, and embedded/explicit literacy. Research indicates that rich home literacy environments and exposure to rich oral language provide an important foundation for the more structured literacy environments of school. Furthermore, there is a wealth of evidence to support a variety of direct and indirect intervention practices in the home, child care, and preschool contexts to support and enhance all aspects of oral and written literacy. Application of this "toolbox" of strategies should enable speech-language pathologists to address the prevention and intervention of literacy deficits within multiple environments during book and play activities. Additionally, clinicians will have techniques to share with parents, child care providers, and preschool teachers for evidence-based literacy instruction within all settings during typical daily

  2. Early attentional bias for negative words when competition is induced.

    Science.gov (United States)

    Ho, Ming-Chou; Li, Shuo-Heng; Yeh, Su-Ling

    2016-05-01

    Previous research (Zeelenberg, Wagenmakers, & Rotteveel, 2006) revealed that emotionally meaningful words were identified significantly better than neutral words, with no difference between positive and negative words. Since in that study only a single target word was displayed at a time, we hypothesized that the equivalent performances for positive and negative words were due to a lack of competition. To test this, in our Experiment 1, we replicated Zeelenberg and colleagues' finding, using emotion-laden Chinese words and the identical data-limited method, which measured the accuracy of a briefly shown target. We then introduced competition in Experiment 2 by simultaneously presenting two words during the target frame, and found evidence for an early attentional bias to negative words. In Experiment 3, we confirmed that the bias in Experiment 2 was not due to the inevitable repetition of stimuli. Taken together, these results support our hypothesis that, in the presence of competition, negative words receive attentional priority and consequently have enhanced perceptual representations.

  3. Risk Factors of Contrast-induced Acute Kidney Injury in Patients Undergoing Emergency Percutaneous Coronary Intervention.

    Science.gov (United States)

    Yuan, Ying; Qiu, Hong; Hu, Xiao-Ying; Luo, Tong; Gao, Xiao-Jin; Zhao, Xue-Yan; Zhang, Jun; Wu, Yuan; Yan, Hong-Bing; Qiao, Shu-Bin; Yang, Yue-Jin; Gao, Run-Lin

    Previous studies of contrast-induced acute kidney injury (CI-AKI) were mostly based on selective percutaneous coronary intervention (PCI) cases, and risk factors of CI-AKI after emergency PCI are unclear. The aim of this study was to explore the risk factors of CI-AKI in a Chinese population undergoing emergency PCI. A total of 1061 consecutive patients undergoing emergency PCI during January 2013 and June 2015 were enrolled and divided into CI-AKI and non-CI-AKI group. Univariable and multivariable analyses were used to identify the risk factors of CI-AKI in emergency PCI patients. CI-AKI was defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dl (44.2 μmol/L) above baseline within 3 days after exposure to contrast medium. The incidence of CI-AKI in patients undergoing emergency PCI was 22.7% (241/1061). Logistic multivariable analysis showed that body surface area (BSA) (odds ratio [OR] 0.213, 95% confidence interval [CI]: 0.075-0.607, P= 0.004), history of myocardial infarction (MI) (OR 1.642, 95% CI: 1.079-2.499, P= 0.021), left ventricular ejection fraction (LVEF) (OR 0.969, 95% CI: 0.944-0.994, P= 0.015), hemoglobin (Hb) (OR 0.988, 95% CI: 0.976-1.000, P= 0.045), estimated glomerular filtration rate (OR 1.027, 95% CI: 1.018-1.037, P < 0.001), left anterior descending (LAD) stented (OR 1.464, 95% CI: 1.000-2.145, P= 0.050), aspirin (OR 0.097, 95%CI: 0.009-0.987, P= 0.049), and diuretics use (OR 1.850, 95% CI: 1.233-2.777, P= 0.003) were independent predictors of CI-AKI in patients undergoing emergency PCI. History of MI, low BSA, LVEF and Hb level, LAD stented, and diuretics use are associated with increased risk of CI-AKI in patients undergoing emergency PCI.

  4. Early remodeling of rat cardiac muscle induced by swimming training

    Directory of Open Access Journals (Sweden)

    Verzola R.M.M.

    2006-01-01

    Full Text Available The aim of the present investigation was to study the effect of acute swimming training with an anaerobic component on matrix metallopeptidase (MMP activity and myosin heavy chain gene expression in the rat myocardium. Animals (male Wistar rats, weighing approximately 180 g were trained for 6 h/day in 3 sessions of 2 h each for 1 to 5 consecutive days (N = 5 rats per group. Rats swam in basins 47 cm in diameter and 60 cm deep filled with water at 33 to 35ºC. After the training period a significant increase (P < 0.05 was observed in the heart weight normalized to body weight by about 22 and 35% in the groups that trained for 96 and 120 h, respectively. Blood lactate levels were significantly increased (P < 0.05 in all groups after all training sessions, confirming an anaerobic component. However, lactate levels decreased (P < 0.05 with days of training, suggesting that the animals became adapted to this protocol. Myosin heavy chain-ß gene expression, analyzed by real time PCR and normalized with GAPDH gene expression, showed a significant two-fold increase (P < 0.01 after 5 days of training. Zymography analysis of myocardium extracts indicated a single ~60-kDa activity band that was significantly increased (P < 0.05 after 72, 96, and 120 h, indicating an increased expression of MMP-2 and suggesting precocious remodeling. Furthermore, the presence of MMP-2 was confirmed by Western blot analysis, but not the presence of MMP-1 and MMP-3. Taken together, our results indicate that in these training conditions, the rat heart undergoes early biochemical and functional changes required for the adaptation to the new physiological condition by tissue remodeling.

  5. A first-principles model of early evolution: emergence of gene families, species, and preferred protein folds.

    Directory of Open Access Journals (Sweden)

    Konstantin B Zeldovich

    2007-07-01

    Full Text Available In this work we develop a microscopic physical model of early evolution where phenotype--organism life expectancy--is directly related to genotype--the stability of its proteins in their native conformations-which can be determined exactly in the model. Simulating the model on a computer, we consistently observe the "Big Bang" scenario whereby exponential population growth ensues as soon as favorable sequence-structure combinations (precursors of stable proteins are discovered. Upon that, random diversity of the structural space abruptly collapses into a small set of preferred proteins. We observe that protein folds remain stable and abundant in the population at timescales much greater than mutation or organism lifetime, and the distribution of the lifetimes of dominant folds in a population approximately follows a power law. The separation of evolutionary timescales between discovery of new folds and generation of new sequences gives rise to emergence of protein families and superfamilies whose sizes are power-law distributed, closely matching the same distributions for real proteins. On the population level we observe emergence of species--subpopulations that carry similar genomes. Further, we present a simple theory that relates stability of evolving proteins to the sizes of emerging genomes. Together, these results provide a microscopic first-principles picture of how first-gene families developed in the course of early evolution.

  6. Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five

    NARCIS (Netherlands)

    Mulder, Hanna; Verhagen, Josje; Van Der Ven, Sanne H. G.; Slot, Pauline L.; Leseman, Paul

    2017-01-01

    Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three

  7. An archaeological search for the emergence of early humans in West Africa

    Directory of Open Access Journals (Sweden)

    Jock M. Agai

    2014-09-01

    Full Text Available Fossils of early humans and their ancestors dating back to millions of years have not yet been found in West Africa. Tools made of bones, stones, and wood suggesting use by early humans or their ancestors have however been found in some parts of West Africa. This research investigates the possible origins and West African indigenous influences on the manufacture and use of these tools. The purpose of this research is to stimulate interest into the study of West African archaeology and palaeontology.

  8. The Common Alerting Protocol (CAP) and Emergency Data Exchange Language (EDXL) - Application in Early Warning Systems for Natural Hazard

    Science.gov (United States)

    Lendholt, Matthias; Hammitzsch, Martin; Wächter, Joachim

    2010-05-01

    The Common Alerting Protocol (CAP) [1] is an XML-based data format for exchanging public warnings and emergencies between alerting technologies. In conjunction with the Emergency Data Exchange Language (EDXL) Distribution Element (-DE) [2] these data formats can be used for warning message dissemination in early warning systems for natural hazards. Application took place in the DEWS (Distance Early Warning System) [3] project where CAP serves as central message format containing both human readable warnings and structured data for automatic processing by message receivers. In particular the spatial reference capabilities are of paramount importance both in CAP and EDXL. Affected areas are addressable via geo codes like HASC (Hierarchical Administrative Subdivision Codes) [4] or UN/LOCODE [5] but also with arbitrary polygons that can be directly generated out of GML [6]. For each affected area standardized criticality values (urgency, severity and certainty) have to be set but also application specific key-value-pairs like estimated time of arrival or maximum inundation height can be specified. This enables - together with multilingualism, message aggregation and message conversion for different dissemination channels - the generation of user-specific tailored warning messages. [1] CAP, http://www.oasis-emergency.org/cap [2] EDXL-DE, http://docs.oasis-open.org/emergency/edxl-de/v1.0/EDXL-DE_Spec_v1.0.pdf [3] DEWS, http://www.dews-online.org [4] HASC, "Administrative Subdivisions of Countries: A Comprehensive World Reference, 1900 Through 1998" ISBN 0-7864-0729-8 [5] UN/LOCODE, http://www.unece.org/cefact/codesfortrade/codes_index.htm [6] GML, http://www.opengeospatial.org/standards/gml

  9. Emergence of a utopian vision of modernist and futuristic houses and cities in early 20th century

    Science.gov (United States)

    Ma, Nan

    2017-04-01

    Throughout the development of literature on urban design theories, utopian thinking has played a crucial role as utopians were among the first designers. Many unrealized utopian projects such as The Radiant City, have presented a research laboratory and positive attempts for all architects, urban designers and theorists. In this essay, a utopian vision following under More’s and Jameson’s definitions is discussed, examining how the utopian vision of modernist and futuristic houses and cities emerged in the early twentieth century in response to several factors, what urban utopia aimed to represent, and how such version was represented in the built form and the urban landscapes.

  10. Training induces cognitive bias: the case of a simulation-based emergency airway curriculum.

    Science.gov (United States)

    Park, Christine S; Stojiljkovic, Ljuba; Milicic, Biljana; Lin, Brian F; Dror, Itiel E

    2014-04-01

    Training-induced cognitive bias may affect performance. Using a simulation-based emergency airway curriculum, we tested the hypothesis that curriculum design would induce bias and affect decision making. Twenty-three novice anesthesiology residents were randomized into 2 groups. The primary outcome measure was the initiation of supraglottic airway and cricothyroidotomy techniques in a simulated cannot-ventilate, cannot-intubate scenario during 3 evaluation sessions. Secondary outcomes were response times for device initiation. After a baseline evaluation and didactic lecture, residents received an initial practical training in either surgical cricothyroidotomy (CRIC group) or supraglottic airway (SGA group). After the midtest, the groups switched to receive the alternate training. From baseline to midtest, the SGA group increased initiation of supraglottic airway but not cricothyroidotomy. The CRIC group increased initiation of cricothyroidotomy but not supraglottic airway. After completion of training in both techniques, the SGA group increased initiation of both supraglottic airway and cricothyroidotomy. In contrast, the CRIC group increased initiation of cricothyroidotomy but failed to change practice in supraglottic airway. Final test response times showed that the CRIC group was slower to initiate supraglottic airway and faster to initiate cricothyroidotomy. Practical training in only 1 technique caused bias in both groups despite a preceding didactic lecture. The chief finding was an asymmetrical effect of training sequence even after training in both techniques. Initial training in cricothyroidotomy caused bias that did not correct despite subsequent supraglottic airway training. Educators must be alert to the risk of inducing cognitive bias when designing curricula.

  11. Federal Financial Incentives to Induce Early Experience Producing Unconventional Liquid Fuels

    Science.gov (United States)

    2008-01-01

    to Induce Early Experience Producing Unconventional Liquid Fuels Frank Camm, James T. Bartis, Charles J. Bushman Prepared for the United States Air... Frank Camm (Frank_Camm@rand.org). v Contents Preface...common in agreements between oil producers and governments outside the United States (Kretzschmar and Kirchner , 2007; see also Metcalf, 2006). These

  12. Transcranial magnetic stimulation-induced 'visual echoes' are generated in early visual cortex

    NARCIS (Netherlands)

    Jolij, Jacob; Lamme, Victor A. F.

    2010-01-01

    Transcranial magnetic stimulation (TMS) of the early visual areas can trigger perception of a flash of light, a so-called phosphene. Here we show that a very brief presentation of a stimulus can modulate features of a subsequent TMS-induced phosphene, to a level that participants mistake phosphenes

  13. The Emergence of Early Intervention for Children with Hearing Loss in China

    Science.gov (United States)

    Shenglin, Liu; Raver, Sharon A.

    2011-01-01

    In the last decade, China began developing early intervention services for very young children with hearing loss, and their families. This article presents a broad description of some of these programs, including the national rehabilitation networks for speech and hearing training, increased attention on the development of professionals, the…

  14. Temperamental, Parental, and Contextual Contributors to Early-Emerging Internalizing Problems: A New Integrative Analysis Approach

    Science.gov (United States)

    Mills, Rosemary S. L.; Hastings, Paul D.; Helm, Jonathan; Serbin, Lisa A.; Etezadi, Jamshid; Stack, Dale M.; Schwartzman, Alex E.; Li, Hai Hong

    2012-01-01

    This study evaluated a comprehensive model of factors associated with internalizing problems (IP) in early childhood, hypothesizing direct, mediated, and moderated pathways linking child temperamental inhibition, maternal overcontrol and rejection, and contextual stressors to IP. In a novel approach, three samples were integrated to form a large…

  15. Assessing the sociocultural impacts of emerging molecular technologies for the early diagnosis of Alzheimer's disease

    NARCIS (Netherlands)

    Boenink, M.; Cuijpers, Y.M.; Laan, A.L.; Lente, H. van; Moors, E.H.M.

    2011-01-01

    Novel technologies for early diagnosis of Alzheimer’s disease (AD) will impact the way society views and deals with AD and ageing. However, such “sociocultural” impacts are hardly acknowledged in standard approaches of technology assessment. In this paper, we outline three steps to assess such

  16. Strategies for coping with stress in emergency medicine: Early education is vital

    Directory of Open Access Journals (Sweden)

    Gillian R Schmitz

    2012-01-01

    Full Text Available Introduction: Physician burnout has received considerable attention in the literature and impacts a large number of emergency medicine physicians, but there is no standardized curriculum for wellness in resident education. A culture change is needed to educate about wellness, adopt a preventative and proactive approach, and focus on resiliency. Discussion: We describe a novel approach to wellness education by focusing on resiliency rather than the unintended endpoint of physician burnout. One barrier to adoption of wellness education has been establishing legitimacy among emergency medicine (EM residents and educators. We discuss a change in the language of wellness education and provide several specific topics to facilitate the incorporation of these topics in resident education. Conclusion: Wellness education and a culture of training that promotes well-being will benefit EM residents. Demonstrating the impact of several factors that positively affect emergency physicians may help to facilitate alert residents to the importance of practicing activities that will result in wellness. A change in culture and focus on resiliency is needed to adequately address and optimize physician self-care.

  17. Wound emergencies: the importance of assessment, documentation, and early treatment using a wound electronic medical record.

    Science.gov (United States)

    Golinko, Michael S; Clark, Sunday; Rennert, Robert; Flattau, Anna; Boulton, Andrew J M; Brem, Harold

    2009-05-01

    Chronic wounds such as diabetic foot ulcers, venous ulcers, and pressure ulcers are a major source of morbidity and mortality. To describe wound characteristics associated with a wound emergency, the Wound Electronic Medical Records (WEMR) of 200 consecutive admissions (139 patients, average number of admissions 1.4) to a dedicated inpatient wound healing unit over a period of 5 months were retrospectively reviewed. Patient mean age was 62 +/- 16 years, 59% were men, 27% had a foot ulcer and diabetes mellitus, and 29% had venous ulcers. Presenting signs and symptoms included wound pain, cellulitis, nonpurulent drainage, and undermining, but few presented with classic local clinical signs of infection. Treatment consisted of sharp debridement with deep tissue culture and pathology from the wound base and/or systemic antibiotics. Twenty-percent (20%) of patients had pathology-confirmed and 38% had pathology- or radiology-confirmed osteomyelitis on admission, supporting that new or increasing wound pain, cellulitis, and/or nonpurulent drainage or presence of significant undermining may be indicative of an invasive infection and that patients presenting with these signs and symptoms require an immediate treatment plan and consideration of hospital admission. Use of an objective documentation system such as the WEMR may help alert clinicians to subtle wound changes that require aggressive treatment; thereby, avoiding emergency room visits and hospital admissions. Future research is needed utilizing the WEMR across multiple medical centers to further define criteria for a chronic wound emergency.

  18. Emerging Cardiac Imaging Modalities for the Early Detection of Cardiotoxicity Due to Anticancer Therapies.

    Science.gov (United States)

    López-Fernández, Teresa; Thavendiranathan, Paaladinesh

    2017-06-01

    The undeniable advances in the field of oncology have finally led to a decrease in overall cancer-related mortality. However, this population of long-term cancer survivors is now facing a shift toward a substantial increase in cardiovascular morbidity and mortality. Because the development of overt cardiotoxicity can be associated with poor outcomes, preclinical identification of cardiac toxicity is important. This will promote early instauration of treatments to prevent overt heart dysfunction and allow oncologists to continue cancer therapy in an uninterrupted manner. Surveillance strategies for the early detection of cardiac injury include cardiac imaging and biomarkers during treatment. In this review, we outline existing cardiac imaging modalities to detect myocardial changes in patients undergoing cancer treatment and in survivors, and their strengths and limitations. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  19. Early awareness of emerging risks associated with food and feed production: Synopsis of pertinent work carried out within the SAFE FOODS project

    NARCIS (Netherlands)

    Marvin, H.J.P.; Kleter, G.A.

    2009-01-01

    This introduction to the journal¿s supplement on emerging food and feed safety issues summarizes the objectives and activities of the EU-funded SAFE FOODS project in general and its work package focusing on the early identification of emerging food safety risks, in particular. Within this work

  20. Changes in Gene Expression during G-CSF-Induced Emergency Granulopoiesis in Humans

    DEFF Research Database (Denmark)

    Pedersen, Corinna C.; Borup, Rehannah; Fischer-Nielsen, Anne

    2016-01-01

    individuals after 5 d of G-CSF administration. Neutrophil precursors were sorted into discrete stages of maturation by flow cytometry, and RNA was subjected to microarray analysis. mRNA levels were compared with previously published expression levels in corresponding populations of neutrophil precursors...... the levels of four of five measured granule proteins in mature neutrophils, including the proantibacterial protein hCAP-18, which was completely deficient in neutrophils from G-CSF-treated donors. These results indicate that multiple biological processes are altered to satisfy the increased demand......-CSF stimulation on the transcriptome of neutrophils and their precursors have not yet been investigated in humans. In this work, we examine the changes in mRNA expression induced by administration of G-CSF in vivo, as a model of emergency granulopoiesis in humans. Blood samples were collected from healthy...

  1. Population structure induces a symmetry breaking favoring the emergence of cooperation.

    Directory of Open Access Journals (Sweden)

    Jorge M Pacheco

    2009-12-01

    Full Text Available The evolution of cooperation described in terms of simple two-person interactions has received considerable attention in recent years, where several key results were obtained. Among those, it is now well established that the web of social interaction networks promotes the emergence of cooperation when modeled in terms of symmetric two-person games. Up until now, however, the impacts of the heterogeneity of social interactions into the emergence of cooperation have not been fully explored, as other aspects remain to be investigated. Here we carry out a study employing the simplest example of a prisoner's dilemma game in which the benefits collected by the participants may be proportional to the costs expended. We show that the heterogeneous nature of the social network naturally induces a symmetry breaking of the game, as contributions made by cooperators may become contingent on the social context in which the individual is embedded. A new, numerical, mean-field analysis reveals that prisoner's dilemmas on networks no longer constitute a defector dominance dilemma--instead, individuals engage effectively in a general coordination game. We find that the symmetry breaking induced by population structure profoundly affects the evolutionary dynamics of cooperation, dramatically enhancing the feasibility of cooperators: cooperation blooms when each cooperator contributes the same cost, equally shared among the plethora of games in which she participates. This work provides clear evidence that, while individual rational reasoning may hinder cooperative actions, the intricate nature of social interactions may effectively transform a local dilemma of cooperation into a global coordination problem.

  2. Early recognition of intraventricular hemorrhage in the setting of thrombocytosis in the emergency department

    Directory of Open Access Journals (Sweden)

    Charles M

    2016-05-01

    Full Text Available Marvinia Charles, Romy Fontoura, Gregory Sugalski Department of Emergency Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA Abstract: Thrombocytosis is frequently encountered as an incidental laboratory finding since isolated thrombocytosis is often asymptomatic. Even though thrombocytosis is benign and self-limiting in most cases, it can at times result in thrombosis or hemorrhage. The most common type of thrombocytosis is reactive (secondary thrombocytosis and can be due to infections, trauma, surgery, or occult malignancy. Since thrombocytosis is a known risk factor for thrombosis, it is commonly a concern for ischemic stroke and myocardial infarction. Much less common are hemorrhagic events associated with thrombocytosis. Studies have shown that when hemorrhage is present in patients with thrombocytosis, it is most often seen in the setting of chronic myelogenous leukemia and essential thrombocythemia. In essential thrombocythemia, the overall risk of bleeding and thrombosis is 0.33% per patient-year and 6.6% per patient-year, respectively. In the general population, the risk of bleeding and thrombosis is 0% and 1.2%, respectively. The present study is a case report of an 83-year-old man who presented to the emergency department with hypertension and headache, who was then found to have significant thrombocytosis (platelets >1,000×109/L and acute right intraventricular hemorrhage without any signs of neurological deficits, or evidence of vascular malformations or mass. We present this case report for review and discussion of some of the challenges and considerations associated with the management of such patients. Keywords: thrombocytosis, thrombocythemia, hemorrhage, intraventricular hemorrhage, thrombosis, headache, emergency department

  3. Modeling climate impact on an emerging disease, the Phytophthora alni-induced alder decline.

    Science.gov (United States)

    Aguayo, Jaime; Elegbede, Fabrice; Husson, Claude; Saintonge, François-Xavier; Marçais, Benoît

    2014-10-01

    Alder decline caused by Phytophthora alni is one of the most important emerging diseases in natural ecosystems in Europe, where it has threatened riparian ecosystems for the past 20 years. Environmental factors, such as mean site temperature and soil characteristics, play an important role in the occurrence of the disease. The objective of the present work was to model and forecast the effect of environment on the severity of alder Phytophthora outbreaks, and to determine whether recent climate change might explain the disease emergence. Two alder sites networks in NE and SW France were surveyed to assess the crown health of trees; the oomycete soil inoculum was also monitored in the NE network. The main factors explaining the temporal annual variation in alder crown decline or crown recovery were the mean previous winter and previous summer temperatures. Both low winter temperatures and high summer temperatures were unfavorable to the disease. Cold winters promoted tree recovery because of poor survival of the pathogen, while hot summer temperature limited the incidence of tree decline. An SIS model explaining the dynamics of the P. alni-induced alder decline was developed using the data of the NE site network and validated using the SW site network. This model was then used to simulate the frequency of declining alder over time with historical climate data. The last 40 years' weather conditions have been generally favorable to the establishment of the disease, indicating that others factors may be implicated in its emergence. The model, however, showed that the climate of SW France was much more favorable for the disease than that of the Northeast, because it seldom limited the overwintering of the pathogen. Depending on the European area, climate change could either enhance or decrease the severity of the alder decline. © 2014 John Wiley & Sons Ltd.

  4. Emergence of noise-induced oscillations in the central circadian pacemaker.

    Directory of Open Access Journals (Sweden)

    Caroline H Ko

    2010-10-01

    Full Text Available Bmal1 is an essential transcriptional activator within the mammalian circadian clock. We report here that the suprachiasmatic nucleus (SCN of Bmal1-null mutant mice, unexpectedly, generates stochastic oscillations with periods that overlap the circadian range. Dissociated SCN neurons expressed fluctuating levels of PER2 detected by bioluminescence imaging but could not generate circadian oscillations intrinsically. Inhibition of intercellular communication or cyclic-AMP signaling in SCN slices, which provide a positive feed-forward signal to drive the intracellular negative feedback loop, abolished the stochastic oscillations. Propagation of this feed-forward signal between SCN neurons then promotes quasi-circadian oscillations that arise as an emergent property of the SCN network. Experimental analysis and mathematical modeling argue that both intercellular coupling and molecular noise are required for the stochastic rhythms, providing a novel biological example of noise-induced oscillations. The emergence of stochastic circadian oscillations from the SCN network in the absence of cell-autonomous circadian oscillatory function highlights a previously unrecognized level of circadian organization.

  5. Theory of mind in emerging reading comprehension: a longitudinal study of early indirect and direct effects

    OpenAIRE

    Atkinson, Lynette; Slade, Lance; Powell, Daisy; Levy, Joseph P.

    2017-01-01

    The relation between children’s theory of mind (ToM) and emerging reading comprehension was investigated in a longitudinal study over 2.5 years. 80 children were tested for ToM, decoding, language skills and executive function (EF) at Time 1 (mean age = 3:10 years). At Time 2 (mean age = 6:03 years) children's word reading efficiency, language skills and reading comprehension were measured. Mediation analysis showed that ToM at Time 1, when children were around four years old, indirectly pred...

  6. A working procedure for identifying emerging food safety issues at an early stage: Implications for European and international risk management practices

    NARCIS (Netherlands)

    Marvin, H.J.P.; Kleter, G.A.; Frewer, L.J.; Cope, S.F.; Wentholt, M.T.A.; Rowe, G.

    2009-01-01

    There is a need for early identification of emerging food safety issues in order to prevent them from developing into health risks. In this paper, various existing methods and procedures which can be used for early identification of safety issues are reviewed, including the monitoring of the

  7. A Chernobyl lesson for aerial monitoring: integration of passive measurements with active sampling in the emergency early phase

    Energy Technology Data Exchange (ETDEWEB)

    Castelluccio, D.; Cisbani, E.; Fratoni, R.; Frullani, S.; Giuliani, F.; Mostarda, A.; Pierangeli, L.; Veneroni, P. [Istituto Superiore di Sanita, Technologies and Health Dept., Rome (Italy); Chiavarini, S. [Centro Ricerche della Casaccia, ENEA, Rome (Italy); Delprato, U. [IES Solutions srl, Rome (Italy); Fragasso, G.; Siciliano, G. [Galileo Avionica S.p.A., Campidi Bisenzio FI (Italy); Gaddini, M.; Pianese, E. [Central Direction for Emergency and Technical Rescue, Ministry of Interior, Rome (Italy); Marchiori, C.; Paoloni, G. [Roma Univ. La Sapienza, Dipt. di Meccanica e Aeronautica, Facolta di Ingegneria (Italy); Sbuelz, A. [Iniziative Industriali Italiane S.p.A., Rome (Italy)

    2006-07-01

    In our experience, the first quantitative measurement of a contamination parameter has been only possible after many days from the beginning of the accident. Indeed with aerial monitoring systems in use, the quantification of the source activity, or the ground contamination, through the analysis of the gamma ray spectra measured, is only possible with the assumption of a source pattern (localized for a point-like source, diffused for ground surface contamination). In case of a more complex situation, there is not a suitable knowledge to model the radiation source; therefore the measurements can only supply qualitative information. This is the case, both in near and far field, when the radioactive plume released by an accident is passing over the country. The lack of quantitative measurements and the derived uncertainty in forecasting the propagation of the radioactive contamination, does not help the emergency management in the most critical phase, i.e. when countermeasures have to be decided in a preventive way and some risk of negative effects is inevitably linked to their enforcement. A different tool for the emergency management should be provided. An aerial platform instrumented for in-plume measurements, aiming to characterize the extension, composition and concentration of the radioactive mixture in the plume, as well as to measure in situ meteorological parameters could be of invaluable help in the emergency early phase. During last years research and manufacturing activities have been developed to reach these goals. (authors)

  8. The role of population origin and microenvironment in seedling emergence and early survival in Mediterranean maritime pine (Pinus pinaster Aiton.

    Directory of Open Access Journals (Sweden)

    Natalia Vizcaíno-Palomar

    Full Text Available Understanding tree recruitment is needed to forecast future forest distribution. Many studies have reported the relevant ecological factors that affect recruitment success in trees, but the potential for genetic-based differences in recruitment has often been neglected. In this study, we established a semi-natural reciprocal sowing experiment to test for local adaptation and microenvironment effects (evaluated here by canopy cover in the emergence and early survival of maritime pine (Pinus pinaster Aiton, an emblematic Mediterranean forest tree. A novel application of molecular markers was also developed to test for family selection and, thus, for potential genetic change over generations. Overall, we did not find evidence to support local adaptation at the recruitment stage in our semi-natural experiment. Moreover, only weak family selection (if any was found, suggesting that in stressful environments with low survival, stochastic processes and among-year climate variability may drive recruitment. Nevertheless, our study revealed that, at early stages of recruitment, microenvironments may favor the population with the best adapted life strategy, irrespectively of its (local or non-local origin. We also found that emergence time is a key factor for seedling survival in stressful Mediterranean environments. Our study highlights the complexity of the factors influencing the early stages of establishment of maritime pine and provides insights into possible management actions aimed at environmental change impact mitigation. In particular, we found that the high stochasticity of the recruitment process in stressful environments and the differences in population-specific adaptive strategies may difficult assisted migration schemes.

  9. New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

    Science.gov (United States)

    Kotova, Svetlana; Wong, Raymond M; Cameron, Robert B

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. PMID:25670913

  10. New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

    International Nuclear Information System (INIS)

    Kotova, Svetlana; Wong, Raymond M; Cameron, Robert B

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease

  11. Emerging role of Lipopolysaccharide binding protein in sepsis-induced acute kidney injury.

    Science.gov (United States)

    Stasi, Alessandra; Intini, Angelica; Divella, Chiara; Franzin, Rossana; Montemurno, Eustacchio; Grandaliano, Giuseppe; Ronco, Claudio; Fiaccadori, Enrico; Pertosa, Giovanni Battista; Gesualdo, Loreto; Castellano, Giuseppe

    2017-01-01

    Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of the major complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra-glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial-to-mesenchymal transition (EndMT). Gram-negative bacteria and their cell wall component lipopolysaccharides (LPSs) are frequently involved in the pathogenesis of AKI. The host recognition of LPS requires a specific receptor, which belongs to the Toll-like receptor (TLR) family of proteins, called TLR4, and two carrier proteins, namely the LPS-binding protein (LBP) and cluster of differentiation 14 (CD14). In particular, LBP is released as a consequence of Gram-negative infection and maximizes the activation of TLR4 signalling. Recent findings regarding the emerging role of LBP in mediating sepsis-induced AKI, and the possible beneficial effects resulting from the removal of this endogenous adaptor protein, will be discussed in this review. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. Ca2+-Induced Mitochondrial ROS Regulate the Early Embryonic Cell Cycle

    Directory of Open Access Journals (Sweden)

    Yue Han

    2018-01-01

    Full Text Available Summary: While it is appreciated that reactive oxygen species (ROS can act as second messengers in both homeostastic and stress response signaling pathways, potential roles for ROS during early vertebrate development have remained largely unexplored. Here, we show that fertilization in Xenopus embryos triggers a rapid increase in ROS levels, which oscillate with each cell division. Furthermore, we show that the fertilization-induced Ca2+ wave is necessary and sufficient to induce ROS production in activated or fertilized eggs. Using chemical inhibitors, we identified mitochondria as the major source of fertilization-induced ROS production. Inhibition of mitochondrial ROS production in early embryos results in cell-cycle arrest, in part, via ROS-dependent regulation of Cdc25C activity. This study reveals a role for oscillating ROS levels in early cell cycle regulation in Xenopus embryos. : Han et al. show that the fertilization-triggered calcium wave induces reactive oxygen species production from mitochondria, which oscillate with each cell division in Xenopus embryos. Moreover, they demonstrate that inhibition of mitochondrial ROS production disrupts cell cycle progression. Keywords: mitochondria, reactive oxygen species, ROS, Xenopus, Cdc25C, cell cycle, fertilization, Ca2+ wave, HyPer, respiratory burst

  13. Independent Contributions of Early Positive Parenting and Mother-Son Coercion on Emerging Social Development.

    Science.gov (United States)

    Akcinar, Berna; Shaw, Daniel S

    2018-06-01

    In the current study, we explored associations between parent-child coercion and positive parenting in the toddler period in relation to children's social-behavioral development during the school-age period. The data were drawn from the Pitt Mother & Child Project, a sample of 310 low-income, ethnically diverse boys. Drawing on tenets of both attachment and social learning theory, it was hypothesized that coercive mother-son interaction would lead to reductions in positive maternal parenting in the toddler period, and that both positive parenting and mother-son coercion in the toddler period would contribute to children's conduct problems at school entry and lower social skills and peer rejection in middle childhood. The results were largely confirmed, such that mother-son coercive interaction at 18 months was related to decreases in positive parenting at 24 months. Additionally, mother-son coercive interaction and positive parenting at 24 months were linked to child conduct problems at age 5, which in turn predicted child social skills and peer rejection during middle childhood. In addition to indirect effects through child conduct problems, mother-son coercion continued to be independently related to school-age peer rejection. The findings are discussed with respect to the importance of early coercive interactions in the growth of child social-behavioral development from early to middle childhood.

  14. Semantic Wavelet-Induced Frequency-Tagging (SWIFT Periodically Activates Category Selective Areas While Steadily Activating Early Visual Areas.

    Directory of Open Access Journals (Sweden)

    Roger Koenig-Robert

    Full Text Available Primate visual systems process natural images in a hierarchical manner: at the early stage, neurons are tuned to local image features, while neurons in high-level areas are tuned to abstract object categories. Standard models of visual processing assume that the transition of tuning from image features to object categories emerges gradually along the visual hierarchy. Direct tests of such models remain difficult due to confounding alteration in low-level image properties when contrasting distinct object categories. When such contrast is performed in a classic functional localizer method, the desired activation in high-level visual areas is typically accompanied with activation in early visual areas. Here we used a novel image-modulation method called SWIFT (semantic wavelet-induced frequency-tagging, a variant of frequency-tagging techniques. Natural images modulated by SWIFT reveal object semantics periodically while keeping low-level properties constant. Using functional magnetic resonance imaging (fMRI, we indeed found that faces and scenes modulated with SWIFT periodically activated the prototypical category-selective areas while they elicited sustained and constant responses in early visual areas. SWIFT and the localizer were selective and specific to a similar extent in activating category-selective areas. Only SWIFT progressively activated the visual pathway from low- to high-level areas, consistent with predictions from standard hierarchical models. We confirmed these results with criterion-free methods, generalizing the validity of our approach and show that it is possible to dissociate neural activation in early and category-selective areas. Our results provide direct evidence for the hierarchical nature of the representation of visual objects along the visual stream and open up future applications of frequency-tagging methods in fMRI.

  15. Semantic Wavelet-Induced Frequency-Tagging (SWIFT) Periodically Activates Category Selective Areas While Steadily Activating Early Visual Areas.

    Science.gov (United States)

    Koenig-Robert, Roger; VanRullen, Rufin; Tsuchiya, Naotsugu

    2015-01-01

    Primate visual systems process natural images in a hierarchical manner: at the early stage, neurons are tuned to local image features, while neurons in high-level areas are tuned to abstract object categories. Standard models of visual processing assume that the transition of tuning from image features to object categories emerges gradually along the visual hierarchy. Direct tests of such models remain difficult due to confounding alteration in low-level image properties when contrasting distinct object categories. When such contrast is performed in a classic functional localizer method, the desired activation in high-level visual areas is typically accompanied with activation in early visual areas. Here we used a novel image-modulation method called SWIFT (semantic wavelet-induced frequency-tagging), a variant of frequency-tagging techniques. Natural images modulated by SWIFT reveal object semantics periodically while keeping low-level properties constant. Using functional magnetic resonance imaging (fMRI), we indeed found that faces and scenes modulated with SWIFT periodically activated the prototypical category-selective areas while they elicited sustained and constant responses in early visual areas. SWIFT and the localizer were selective and specific to a similar extent in activating category-selective areas. Only SWIFT progressively activated the visual pathway from low- to high-level areas, consistent with predictions from standard hierarchical models. We confirmed these results with criterion-free methods, generalizing the validity of our approach and show that it is possible to dissociate neural activation in early and category-selective areas. Our results provide direct evidence for the hierarchical nature of the representation of visual objects along the visual stream and open up future applications of frequency-tagging methods in fMRI.

  16. Specific synbiotics in early life protect against diet-induced obesity in adult mice

    DEFF Research Database (Denmark)

    Mischke, Mona; Arora, Tulika; Tims, Sebastian

    2018-01-01

    AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health long-lastingly. Here, we determined how beneficial microbiome interventions in early life...... synbiotics protected mice against WSD-induced excessive fat accumulation throughout life, replicable in two independent European animal facilities. Adult insulin sensitivity and dyslipidemia were improved and most pronounced gene expression changes were observed in the ileum. We observed subtle changes...... as preventive measure to ameliorate obesity risk and improve metabolic health throughout life....

  17. Emergent mechanical support in the community: improvement with early transplant center referral.

    Science.gov (United States)

    Morris, Rohinton J; Pochettino, Alberto; O'Hara, Marylou; Gardner, Timothy J; Acker, Michael A

    2005-06-01

    Emergent mechanical support for the failing ventricle, with eventual transfer for definitive care, is often required at non-transplant centers. Transfer for definitive care, in terms of bridge to transplant, may require ventricular assist device (VAD) placement at the primary institution or at the transplant center. Review of consecutive single transplant center referrals was conducted to decipher optimal management. From January 1997 to December 2000, 104 patients were transferred to the University of Pennsylvania Heart Failure/Transplant Service. Most were transferred from active cardiac surgical programs, with 56 patients having post-cardiotomy failure at the primary site. A VAD was placed in procedures done at the outside hospital (OSH) in 28 patients, most commonly (60%) an Abiomed device. Of the 76 patients that received a VAD at the transplant center (TxpC), 86% received a TCI or Thoratec device. Biventricular support was required in 34 patients. Overall survival was 57%, with 54 patients bridged to transplantation and 5 patients undergoing recovery. Patients having a VAD placed at the OSH had a 32% (9 of 28) survival, whereas at the TxpC survival was 65% (45 of 76) (p 1-year post-transplant. The most common cause of death was multi-system organ failure (19 of 45), followed by major neurologic event (15 of 45). Infection was the cause of death in only 6 patients. Left ventricular failure can be treated by emergent VAD placement. Overall survival is substantial if these patients are referred to a transplant center with multiple options. In contrast to previous reports, survival rates may be improved by earlier referral, before VAD placement at non-transplant centers and use of a VAD with longer-term capability.

  18. Erythema ab igne induced by laptop computer: an emerging disease among adolescents?

    Science.gov (United States)

    Brazzelli, V; Grassi, S; Barruscotti, S; Croci, G; Borroni, G

    2015-09-17

    Erythema ab igne (EAI) was a very common disease in the past, when it occurred mainly among people who worked with fire, or in people who had used heat sources in contact with the skin for warming purposes for long time. In the last decades, with the introduction of central heating in the buildings, EAI incidence was remarkably decreased in Western Countries, and it was found almost exclusively among elderly, and in people affected by defects in thermoregulation or alteration of periphery circulation. Recently, a new slight increase of EAI prevalence has been observed, although with some new features. Here, we describe three cases of adolescents who presented with brownish, reticulated patch on the anterior surface of their thighs. An accurate medical questioning revealed that the patients used to place the lower surface of laptop computer on the extensor side of their thighs in a cross-legged position for many hours (about 6-8 hours) every days. In particular, the patients supported the laptop computer always on the same leg. Laptop computer-induced EAI was diagnosed. Only a few cases of laptop computer-induced EAI have been reported in the literature. Although EAI is poorly symptomatic and it generally evolve to complete remission after a early discontinuance of heat source exposure, chronic lesions of EAI have been regarded as precancerous lesions. Therefore, it is important to implement diagnosis and prevention measures of this disease. Dermatologists should consider new causal agents for old diseases.

  19. Management of early pregnancy failure and induced abortion by family medicine educators.

    Science.gov (United States)

    Herbitter, Cara; Bennett, Ariana; Schubert, Finn D; Bennett, Ian M; Gold, Marji

    2013-01-01

    Reproductive health care, including treatment of early pregnancy failure (EPF) and induced abortion, is an integral part of patient-centered care provided by family physicians, but data suggest that comprehensive training is not widely available to family medicine residents. The purpose of this study was to assess EPF and induced abortion management practices and attitudes of family medicine physician educators throughout the United States and Canada. These data were collected as part of a cross-sectional survey conducted by the Council of Academic Family Medicine Educational Research Alliance that was distributed via E-mail to 3152 practicing physician members of Council of Academic Family Medicine organizations. The vast majority of respondents (88.2%) had treated EPF, whereas few respondents (15.3%) had provided induced medication or aspiration abortions. Of those who had treated EPF, most had offered medication management (72.7%), whereas a minority had provided aspiration management (16.4%). Almost all respondents (95%) agreed that EPF management is within the scope of family medicine, and nearly three-quarters (73.2%) agreed that early induced abortion is within the scope of family medicine. Our findings suggest that family physician educators are more experienced with EPF management than elective abortion. Given the overlap of skills needed for provision of these services, there is the potential to increase the number of family physician faculty members providing induced abortions.

  20. Gender stereotypes about intellectual ability emerge early and influence children's interests.

    Science.gov (United States)

    Bian, Lin; Leslie, Sarah-Jane; Cimpian, Andrei

    2017-01-27

    Common stereotypes associate high-level intellectual ability (brilliance, genius, etc.) with men more than women. These stereotypes discourage women's pursuit of many prestigious careers; that is, women are underrepresented in fields whose members cherish brilliance (such as physics and philosophy). Here we show that these stereotypes are endorsed by, and influence the interests of, children as young as 6. Specifically, 6-year-old girls are less likely than boys to believe that members of their gender are "really, really smart." Also at age 6, girls begin to avoid activities said to be for children who are "really, really smart." These findings suggest that gendered notions of brilliance are acquired early and have an immediate effect on children's interests. Copyright © 2017, American Association for the Advancement of Science.

  1. Japan's emerging challenge for child abuse: system coordination for early prevention of child abuse is needed.

    Science.gov (United States)

    Takahashi, Kenzo; Kanda, Hideyuki; Sugaya, Nagisa

    2014-08-01

    At the end of 2013, a Japanese newspaper reported that 4,173 children were unidentified or missing in Japan. The article concluded that child abuse was a matter of national concern. In examining the strengths and weaknesses of Japan's welfare system in regard to child abuse, it would seem that a weakness exists with regard to its ambiguity on the roles of different officers who contact suspected cases. Although three types of officer (health, welfare, and police officers) can take charge, child abuse cases might be missed because the division of labor varies between the different types of officer. However, a strength exists in the periodical pediatric health check system that is in place in each of Japan's 1,742 municipalities. To efficiently implement early intervention for child abuse, it is necessary to rearrange the division of labor among the three types of officers to clarify who should intervene in suspected cases.

  2. Move to literacy: fanning emergent literacy in early childhood education in a

    Directory of Open Access Journals (Sweden)

    Lorayne Excell

    2011-12-01

    is contested. This paper argues that an early childhood education (ECE approach, which fans literacy, should follow a quality play-based approach that embraces a pedagogy of play that foregrounds how children learn through play, and how teachers teach through play. In combining two constructs ‘pedagogy’ and ‘play’, we propose an approach that is underpinned by movement and other appropriate learning activities, which support the development of perceptual-motor behaviours and sensorimotor integration in a pedagogy of play. We argue that perceptual-motor behaviours and sensorimotor integration are the ‘invisible’ pathways to literacy. They provide young children with many and varied, incidental, implicit and explicit learning opportunities. A more informal, play-based approach towards teaching and learning appears to be a successful way of nurturing literacy processes.

  3. Extant ape dental topography and its implications for reconstructing the emergence of early Homo.

    Science.gov (United States)

    Berthaume, Michael A; Schroer, Kes

    2017-11-01

    Dental topography reflects diet accurately in several extant and extinct mammalian clades. However, dental topographic dietary reconstructions have high success rates only when closely related taxa are compared. Given the dietary breadth that exists among extant apes and likely existed among fossil hominins, dental topographic values from many species and subspecies of great apes are necessary for making dietary inferences about the hominin fossil record. Here, we present the results of one metric of dental topography, Dirichlet normal energy (DNE), for seven groups of great apes (Pongo pygmaeus pygmaeus, Pan paniscus, Pan troglodytes troglodytes and schweinfurthii, Gorilla gorilla gorilla, Gorilla beringei graueri and beringei). Dirichlet normal energy was inadequate at differentiating folivores from frugivores, but was adequate at predicting which groups had more fibrous diets among sympatric African apes. Character displacement analyses confirmed there is substantial dental topographic and relative molar size (M 1 :M 2 ratio; length, width, and area) divergence in sympatric apes when compared to their allopatric counterparts, but character displacement is only present in relative molar size when DNE is also considered. Presence of character displacement is likely due to indirect competition over similar food resources. Assuming similar ecological conditions in the Plio-Pleistocene, the derived masticatory apparatuses of the robust australopiths and early Homo may be due to indirect competition over dietary resources between the taxa, causing dietary niche partitioning. Our results imply that dental topography cannot be used to predict dietary categories in fossil hominins without consideration of ecological factors, such as dietary and geographic overlap. In addition, our results may open new avenues for understanding the community compositions of early hominins and the formation of specific ecological niches among hominin taxa. Copyright © 2017 Elsevier Ltd

  4. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  5. Tn5-induced pBS286 plasmid mutations blocking early stages of napthalene oxidation

    International Nuclear Information System (INIS)

    Kosheleva, I.A.; Tsoi, T.V.; Ivashina, T.V.; Selifonov, S.A.; Starovoitov, I.I.; Boronin, A.M.

    1988-01-01

    The authors present data on the further analysis of the structural and functional organization of the nah region of plasmid pBS286 controlling the constitutive oxidation of naphthalene by Pseudomonas putida cells. They have studied Tn5-induced mutations blocking early stages of naphthalene oxidation. They present and discuss data providing evidence that, in contrast to plasmid NAH7, the mechanism of regulation of the nahl operon of plasmid NPL-1, the parent plasmid of plasmid pBS286, with inducible synthesis of naphthalene dioxygenase can include elements of a negative control with participation of the regulatory locus R, located proximal to the structural nah genes and closely linked to or overlapped by the inverted control DNA segment (4.2 kb). They also present data on the possibility of regulation of the activity of the catechol-splitting meta-pathway genes with the participation of products of early stages of naphthalene oxidation

  6. The Case of the Lacking Carbonates and the Emergence of Early Life on Mars

    Directory of Open Access Journals (Sweden)

    Ricardo Amils

    2010-08-01

    Full Text Available The mineralogical characterization of Mars by different exploration missions, provides a new image of the earliest conditions that prevailed on the planet surface. The detection of extensive deposits of phyllosillicates has been considered to be as a result of the production of hydrated silicates through alteration and precipitation under neutral to sub-alkaline conditions. Although extensive deposits of carbonates should precipitate beneath a thick CO2-bearing atmosphere, only a few outcrops of Mg-rich carbonates have been detected on Mars. Paradoxically those carbonates occur in association with geological units exposed to acidic paleoenvironments. Given such geochemical conditions on Earth, the carbon cycle is intimately associated with life, then, we can assume that the presence or absence of microbial communities should have impacted the distribution of those carbonate compounds on Mars. In this paper, we suggest three potential geobiological scenarios to explain how the emergence of life on Mars would have impacted the carbon cycle and, hence, the formation of carbonates on a planetary scale.

  7. Industry Application Emergency Core Cooling System Cladding Acceptance Criteria Early Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Szilard, Ronaldo H. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Youngblood, Robert W. [FPoliSolutions LLC, Murrysville, PA (United States); Zhang, Hongbin [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zhao, Haihua [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bayless, Paul D. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Frepoli, Cesare [FPoliSolutions LLC, Murrysville, PA (United States); Yurko, Joseph P. [FPoliSolutions LLC, Murrysville, PA (United States); Swindlehurst, Gregg [GS Nuclear Consulting, Charlotte, NC (United States); Zoino, Angelo [Univ. of Rome Tor Vergata (Italy)

    2015-09-01

    The U. S. NRC is currently proposing rulemaking designated as “10 CFR 50.46c” to revise the loss-of-coolant-accident (LOCA)/emergency core cooling system (ECCS) acceptance criteria to include the effects of higher burnup on cladding performance as well as to address other technical issues. The NRC is also currently resolving the public comments with the final rule expected to be issued in April 2016. The impact of the final 50.46c rule on the industry may involve updating of fuel vendor LOCA evaluation models, NRC review and approval, and licensee submittal of new LOCA evaluations or re-analyses and associated technical specification revisions for NRC review and approval. The rule implementation process, both industry and NRC activities, is expected to take 4-6 years following the rule effective date. As motivated by the new rule, the need to use advanced cladding designs may be a result. A loss of operational margin may result due to the more restrictive cladding embrittlement criteria. Initial and future compliance with the rule may significantly increase vendor workload and licensee cost as a spectrum of fuel rod initial burnup states may need to be analyzed to demonstrate compliance. Consequently, there will be an increased focus on licensee decision making related to LOCA analysis to minimize cost and impact, and to manage margin. The proposed rule would apply to a light water reactor and to all cladding types.

  8. Obstructive Apneas Induce Early Release of Mesenchymal Stem Cells into Circulating Blood

    Science.gov (United States)

    Carreras, Alba; Almendros, Isaac; Acerbi, Irene; Montserrat, Josep M.; Navajas, Daniel; Farré, Ramon

    2009-01-01

    Study Objectives: To investigate whether noninvasive application of recurrent airway obstructions induces early release of mesenchymal stem cells into the circulating blood in a rat model of obstructive sleep apnea. Design: Prospective controlled animal study. Setting: University laboratory. Patients or Participants: Twenty male Sprague-Dawley rats (250–300 g). Interventions: A specially designed nasal mask was applied to the anesthetized rats. Ten rats were subjected to a pattern of recurrent obstructive apneas (60 per hour, lasting 15 seconds each) for 5 hours. Ten anesthetized rats were used as controls. Measurements and Results: Mesenchymal stem cells from the blood and bone marrow samples were isolated and cultured to count the total number of colony-forming unit fibroblasts (CFU-F) of adherent cells after 9 days in culture. The number of CFU-F from circulating blood was significantly (P = 0.02) higher in the rats subjected to recurrent obstructive apneas (5.00 ± 1.16; mean ± SEM) than in controls (1.70 ± 0.72). No significant (P = 0.54) differences were observed in CFU-F from bone marrow. Conclusions: Application of a pattern of airway obstructions similar to those experienced by patients with sleep apnea induced an early mobilization of mesenchymal stem cells into circulating blood. Citation: Carreras A; Almendros I; Acerbi I; Montserrat JM; Navajas D; Farré R. Obstructive apneas induce early release of mesenchymal stem cells into circulating blood. SLEEP 2009;32(1):117-119. PMID:19189787

  9. Polyamines affect histamine synthesis during early stages of IL-3-induced bone marrow cell differentiation.

    Science.gov (United States)

    García-Faroldi, Gianni; Correa-Fiz, Florencia; Abrighach, Hicham; Berdasco, María; Fraga, Mario F; Esteller, Manel; Urdiales, José L; Sánchez-Jiménez, Francisca; Fajardo, Ignacio

    2009-09-01

    Mast cells synthesize and store histamine, a key immunomodulatory mediator. Polyamines are essential for every living cell. Previously, we detected an antagonistic relationship between the metabolisms of these amines in established mast cell and basophilic cell lines. Here, we used the IL-3-driven mouse bone marrow-derived mast cell (BMMC) culture system to further investigate this antagonism in a mast cell model of deeper physiological significance. Polyamines and histamine levels followed opposite profiles along the bone marrow cell cultures leading to BMMCs. alpha-Difluoromethylornithine (DFMO)-induced polyamine depletion resulted in an upregulation of histidine decarboxylase (HDC, the histamine-synthesizing enzyme) expression and activity, accompanied by increased histamine levels, specifically during early stages of these cell cultures, where an active histamine synthesis process occurs. In contrast, DFMO did not induce any effect in either HDC activity or histamine levels of differentiated BMMCs or C57.1 mast cells, that exhibit a nearly inactive histamine synthesis rate. Sequence-specific DNA methylation analysis revealed that the DFMO-induced HDC mRNA upregulation observed in early bone marrow cell cultures is not attributable to a demethylation of the gene promoter caused by the pharmacological polyamine depletion. Taken together, the results support an inverse relationship between histamine and polyamine metabolisms during the bone marrow cell cultures leading to BMMCs and, moreover, suggest that the regulation of the histamine synthesis occurring during the early stages of these cultures depends on the concentrations of polyamines. (c) 2009 Wiley-Liss, Inc.

  10. New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

    Directory of Open Access Journals (Sweden)

    Kotova S

    2015-01-01

    Full Text Available Svetlana Kotova,1,2 Raymond M Wong,1–3 Robert B Cameron1,2 1Veterans Affairs Greater Los Angeles Healthcare System, Division of Thoracic Surgery, Los Angeles, CA, USA; 2UCLA Division of Thoracic Surgery and Comprehensive Mesothelioma Program, Los Angeles, CA, USA; 3Pacific Meso Center at the Pacific Heart, Lung and Blood Institute, Los Angeles, CA, USA Abstract: Malignant pleural mesothelioma (MPM is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation, survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4 receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. Keywords: MPM, new targeted, systemic, local therapies

  11. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion.

    Science.gov (United States)

    Barrios, Juliana; Patel, Kruti R; Aven, Linh; Achey, Rebecca; Minns, Martin S; Lee, Yoonjoo; Trinkaus-Randall, Vickery E; Ai, Xingbin

    2017-09-01

    Pulmonary neuroendocrine cells (PNECs) are the only innervated airway epithelial cells. To what extent neural innervation regulates PNEC secretion and function is unknown. Here, we discover that neurotrophin 4 (NT4) plays an essential role in mucus overproduction after early life allergen exposure by orchestrating PNEC innervation and secretion of GABA. We found that PNECs were the only cellular source of GABA in airways. In addition, PNECs expressed NT4 as a target-derived mechanism underlying PNEC innervation during development. Early life allergen exposure elevated the level of NT4 and caused PNEC hyperinnervation and nodose neuron hyperactivity. Associated with aberrant PNEC innervation, the authors discovered that GABA hypersecretion was required for the induction of mucin Muc5ac expression. In contrast, NT4 -/- mice were protected from allergen-induced mucus overproduction and changes along the nerve-PNEC axis without any defects in inflammation. Last, GABA installation restored mucus overproduction in NT4 -/- mice after early life allergen exposure. Together, our findings provide the first evidence for NT4-dependent neural regulation of PNEC secretion of GABA in a neonatal disease model. Targeting the nerve-PNEC axis may be a valid treatment strategy for mucus overproduction in airway diseases, such as childhood asthma.-Barrios, J., Patel, K. R., Aven, L., Achey, R., Minns, M. S., Lee, Y., Trinkaus-Randall, V. E., Ai, X. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion. © FASEB.

  12. Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

    Energy Technology Data Exchange (ETDEWEB)

    Das, Suvarthi [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kumar, Ashutosh [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Seth, Ratanesh Kumar [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Tokar, Erik J. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Kadiiska, Maria B. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Waalkes, Michael P. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Mason, Ronald P. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Chatterjee, Saurabh, E-mail: schatt@mailbox.sc.edu [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States)

    2013-06-15

    Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates

  13. Evolution of time-keeping mechanisms: early emergence and adaptation to photoperiod.

    Science.gov (United States)

    Hut, R A; Beersma, D G M

    2011-07-27

    Virtually all species have developed cellular oscillations and mechanisms that synchronize these cellular oscillations to environmental cycles. Such environmental cycles in biotic (e.g. food availability and predation risk) or abiotic (e.g. temperature and light) factors may occur on a daily, annual or tidal time scale. Internal timing mechanisms may facilitate behavioural or physiological adaptation to such changes in environmental conditions. These timing mechanisms commonly involve an internal molecular oscillator (a 'clock') that is synchronized ('entrained') to the environmental cycle by receptor mechanisms responding to relevant environmental signals ('Zeitgeber', i.e. German for time-giver). To understand the evolution of such timing mechanisms, we have to understand the mechanisms leading to selective advantage. Although major advances have been made in our understanding of the physiological and molecular mechanisms driving internal cycles (proximate questions), studies identifying mechanisms of natural selection on clock systems (ultimate questions) are rather limited. Here, we discuss the selective advantage of a circadian system and how its adaptation to day length variation may have a functional role in optimizing seasonal timing. We discuss various cases where selective advantages of circadian timing mechanisms have been shown and cases where temporarily loss of circadian timing may cause selective advantage. We suggest an explanation for why a circadian timing system has emerged in primitive life forms like cyanobacteria and we evaluate a possible molecular mechanism that enabled these bacteria to adapt to seasonal variation in day length. We further discuss how the role of the circadian system in photoperiodic time measurement may explain differential selection pressures on circadian period when species are exposed to changing climatic conditions (e.g. global warming) or when they expand their geographical range to different latitudes or altitudes.

  14. CF3DODA-Me induces apoptosis, degrades Sp1, and blocks the transformation phase of the blebbishield emergency program.

    Science.gov (United States)

    Taoka, Rikiya; Jinesh, Goodwin G; Xue, Wenrui; Safe, Stephen; Kamat, Ashish M

    2017-05-01

    Cancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF 3 DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from blebbishields as well as transformation in soft agar. These findings confirm CF 3 DODA-Me as a potential therapeutic candidate that can induce apoptosis and block transformation from blebbishields.

  15. Early predictors of narcotics-dependent patients in the emergency department

    Directory of Open Access Journals (Sweden)

    Wei-Che Lee

    2013-06-01

    Full Text Available It is not unusual that narcotics-dependent patients fulfill their medical requirements in the emergency department (ED. The behavior of these patients varies, and their manifestations and predictors are still not fully studied. We performed this retrospective study by prospectively collecting data on patients with suspected drug dependence who were undiagnosed at first and then treated for some kind of reported pain at the ED. Patients who were confirmed to have narcotics dependence were compared with control patients in a ratio of 1:3 matching for age, gender, disease, and clinical diagnoses. From January 2006 to October 2009, 26 of 223 patients treated for pain were found to be drug dependent (12 males and 14 females. The average dose of narcotics used was higher than the control group [3.23 ± 1.14 vs. 1.12 ± 0.36, p < 0.001, confidence interval (CI: 1.648–2.583]. Numbers of patients making unscheduled returns to the ED within 24 hours were significant [24/26 vs. 8/78, p ≤ 0.001, odds ratio (OR 105.00, 95% CI 20.834–529.175]. In addition, patients showing aggressive attitudes were significant (17/26 vs. 2/78, p < 0.001, OR 71.78, 95% CI 14.206–362.663. In the case group, six of them told the physician that they were allergic to medicines other than the particular one they wanted, and three of the six presented injuries that were reported to be in the same (or repeated place for unscheduled returns, which were not found in the control group. In this study, some behaviors were commonly observed in the at-risk group. These patients were prone to manifest some types of symptoms and behaviors, such as uncontrolled pain with three doses of analgesics, aggressive attitude, returning to the ED within 24 hours with the complaint of the same severe pain, repeating the same injury, claiming allergy to other analgesics, and asking for certain analgesics. All these behaviors should alert the physician to suspect a drug-seeking problem.

  16. Superior vena cava syndrome induced by bronchogenic carcinoma: is this an oncological emergency?

    International Nuclear Information System (INIS)

    Gauden, S.J.

    1993-01-01

    This study was initiated to assess the validity of the traditional view that superior vena cava syndrome (SVCS) induced by bronchogenic carcinoma is a life-threatening condition requiring immediate treatment without necessarily obtaining a tissue diagnosis. A retrospective review of 6504 patients diagnosed to have lung cancer and treated at the Queensland Radium Institute between 1979 and 1991 was performed. From this group, 249 patients with well-documented SVCS treated with radiotherapy were identified. An analysis with respect to duration of symptoms, time to treatment, degree of response and overall survival was performed. Although deaths did occur in this series due to associated tracheal obstruction, deaths due to venous compression per se were not seen. The response to radiotherapy was generally poor, with only 19% of patients achieving a complete resolution of their symptoms and signs while 30% of patients had no demonstrable response. The overall survival of patients in the study group was 5% at two years. The median survival for complete responders was 6 months while for non-responders it was 1 month. This study found little evidence to support the concept that SVCS is an oncological emergency. Patients survived despite unrelieved obstruction and the data suggest that the poor prognosis of patients with this condition appears to more closely correlate with the prognosis of the underlying disease. It is suggested that intravascular thrombosis may be an important factor in the pathogenesis of this syndrome. 16 refs., 5 tabs., 5 figs

  17. Taking Up an Active Role: Emerging Participation in Early Mother–Infant Interaction during Peekaboo Routines

    Directory of Open Access Journals (Sweden)

    Iris Nomikou

    2017-10-01

    Full Text Available Dynamical systems approaches to social coordination underscore how participants' local actions give rise to and maintain global interactive patterns and how, in turn, they are also shaped by them. Developmental research can deliver important insights into both processes: (1 the stabilization of ways of interacting, and (2 the gradual shaping of the agentivity of the individuals. In this article we propose that infants' agentivity develops out of participation, i.e., acting a part in an interaction system. To investigate this development this article focuses on the ways in which participation in routinized episodes may shape infant's agentivity in social events. In contrast to existing research addressing more advanced forms of participating in social routines, our goal was to assess infants' early participation as evidence of infants' agentivity. In our study, 19 Polish mother–infant dyads were filmed playing peekaboo when the infants were 4 and 6 months of age. We operationalized infants' participation in the peekaboo in terms of their use of various behaviors across modalities during specific phases of the game: We included smiles, vocalizations, and attempts to cover and uncover themselves or their mothers. We hypothesized that infants and mothers would participate actively in the routine by regulating their behavior so as to adhere to the routine format. Furthermore, we hypothesized that infants who experienced more scaffolding would be able to adopt a more active role in the routine. We operationalized scaffolding as mothers' use of specific peekaboo structures that allowed infants to anticipate when it was their turn to act. Results suggested that infants as young as 4 months of age engaged in peekaboo and took up turns in the game, and that their participation increased at 6 months of age. Crucially, our results suggest that infants' behavior was organized by the global structure of the peekaboo game, because smiles, vocalizations, and

  18. The effects of heavy meteorite bombardment on the early evolution — The emergence of the three Domains of life

    Science.gov (United States)

    Gogarten-Boekels, Maria; Hilario, Elena; Gogarten, J. Peter

    1995-06-01

    A characteristic of many molecular phylogenies is that the three domains of life (Bacteria, Archaea, Eucarya) are clearly separated from each other. The analyses of ancient duplicated genes suggest that the last common ancestor of all presently known life forms already had been a sophisticated cellular prokaryote. These findings are in conflict with theories that have been proposed to explain the absence of deep branching lineages. In this paper we propose an alternative scenario, namely, a large meteorite impact that wiped out almost all life forms present on the early Earth. Following this nearly complete frustation of life on Earth, two surviving extreme thermophilic species gave rise to the now existing major groups of living organisms, the Bacteria and Archaea. [The latter also contributed the major portion to the nucleo-cytoplasmic component of the Eucarya]. An exact calibration of the molecular record with regard to time is not yet possible. The emergence of Eucarya in fossil and molecular records suggests that the proposed late impact should have occurred before 2100 million years before present (BP). If the 3500 million year old microfossils [Schopf, J. W. 1993: Science 260: 640 646] are interpreted as representatives of present day existing groups of bacteria (i.e., as cyanobacteria), then the impact is dated to around 3700 million years BP. The analysis of molecular sequences suggests that the separation between the Eucarya and the two prokaryotic domains is less deep then the separation between Bacteria and Archaea. The fundamental cell biological differences between Archaea and Eucarya were obtained over a comparatively short evolutionary distance (as measured in number of substitution events in biological macromolecules). Our interpretation of the molecular record suggests that life emerged early in Earth's history even before the time of the heavy bombardment was over. Early life forms already had colonized extreme habitats which allowed at least two

  19. Minocycline-Suppression of Early Peripheral Inflammation Reduces Hypoxia-Induced Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Yingjun Min

    2017-09-01

    Full Text Available While extensive studies report that neonatal hypoxia-ischemia (HI induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d rat pups to systemic hypoxia (3.5 h, a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg was injected intraperitoneally (i.p. 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS, indicated by presence of C-C chemokine receptor type 2 (CCR2+/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker. Interrupted blood-brain barrier (BBB, hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response.

  20. Minocycline-Suppression of Early Peripheral Inflammation Reduces Hypoxia-Induced Neonatal Brain Injury

    Science.gov (United States)

    Min, Yingjun; Li, Hongchun; Xu, Kaiyu; Huang, Yilong; Xiao, Jie; Wang, Weizhou; Li, Longjun; Yang, Ting; Huang, Lixuan; Yang, Ling; Jiang, Hong; Wang, Qian; Zhao, Min; Hua, HaiRong; Mei, Rong; Li, Fan

    2017-01-01

    While extensive studies report that neonatal hypoxia-ischemia (HI) induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d) rat pups to systemic hypoxia (3.5 h), a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg) was injected intraperitoneally (i.p.) 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg) minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS), indicated by presence of C-C chemokine receptor type 2 (CCR2+)/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker). Interrupted blood-brain barrier (BBB), hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response. PMID:28955196

  1. Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence

    Science.gov (United States)

    Kenny, Jonathan D.; Taylor, Norman E.; Brown, Emery N.; Solt, Ken

    2015-01-01

    Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg IV), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg IV) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1–4 Hz) to θ (4–8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes

  2. Dextroamphetamine (but Not Atomoxetine Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence.

    Directory of Open Access Journals (Sweden)

    Jonathan D Kenny

    Full Text Available Methylphenidate induces reanimation (active emergence from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each. When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6. After a single dose of propofol (8 mg/kg i.v., the mean emergence times for rats that received normal saline (vehicle and dextroamphetamine (1 mg/kg i.v. were 641 sec and 404 sec, respectively (n = 8 each. The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8, this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1-4 Hz to θ (4-8 Hz during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation

  3. Effects of emergence time and early social rearing environment on behaviour of Atlantic salmon: Consequences for juvenile fitness and smolt migration

    DEFF Research Database (Denmark)

    Larsen, Martin Hage; Johnsson, Jörgen I.; Winberg, Svante

    2015-01-01

    Consistent individual differences in behaviour have been well documented in a variety of animal taxa, but surprisingly little is known about the fitness and life-history consequences of such individual variation. In wild salmonids, the timing of fry emergence from gravel spawning nests has been...... whether behavioural traits measured in the laboratory predict growth, survival, and migration status in the wild. Atlantic salmon fry were sorted with respect to emergence time from artificial spawning nest into three groups: early, intermediate, and late. These emergence groups were hatchery...... no significant effects on survival, growth, and migration status in the stream, although migration propensity was 1.4 to 1.9 times higher for early emerging individuals that were reared separately. In addition, despite individuals showing considerable variation in behaviour across treatment groups...

  4. Early growth response-1 protein is induced by JC virus infection and binds and regulates the JC virus promoter

    International Nuclear Information System (INIS)

    Romagnoli, Luca; Sariyer, Ilker K.; Tung, Jacqueline; Feliciano, Mariha; Sawaya, Bassel E.; Del Valle, Luis; Ferrante, Pasquale; Khalili, Kamel; Safak, Mahmut; White, Martyn K.

    2008-01-01

    JC virus (JCV) is a human polyomavirus that can emerge from a latent state to cause the cytolytic destruction of oligodendrocytes in the brain resulting in the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Previous studies described a cis-acting transcriptional regulatory element in the JCV non-coding control region (NCCR) that is involved in the response of JCV to cytokines. This consists of a 23 base pair GGA/C rich sequence (GRS) near the replication origin (5112 to + 4) that contains potential binding sites for Sp1 and Egr-1. Gel shift analysis showed that Egr-1, but not Sp1, bound to GRS. Evidence is presented that the GRS gel shift seen on cellular stimulation is due to Egr-1. Thus, TPA-induced GRS gel shift could be blocked by antibody to Egr-1. Further, the TPA-induced GRS DNA/protein complex was isolated and found to contain Egr-1 by Western blot. No other Egr-1 sites were found in the JCV NCCR. Functionally, Egr-1 was found to stimulate transcription of JCV late promoter but not early promoter reporter constructs. Mutation of the Egr-1 site abrogated Egr-1 binding and virus with the mutated Egr-1 site showed markedly reduced VP1 expression and DNA replication. Infection of primary astrocytes by wild-type JCV induced Egr-1 nuclear expression that was maximal at 5-10 days post-infection. Finally, upregulation of Egr-1 was detected in PML by immunohistochemistry. These data suggest that Egr-1 induction may be important in the life cycle of JCV and PML pathogenesis

  5. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  6. Aortic VCAM-1: an early marker of vascular inflammation in collagen-induced arthritis.

    Science.gov (United States)

    Denys, Anne; Clavel, Gaëlle; Lemeiter, Delphine; Schischmanoff, Olivier; Boissier, Marie-Christophe; Semerano, Luca

    2016-05-01

    Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  7. Comets as Messengers from the Early Solar System - Emerging Insights on Delivery of Water, Nitriles, and Organics to Earth

    Science.gov (United States)

    Mumma, Michael J.; Charnley, Steven B.

    2012-01-01

    The question of exogenous delivery of water and organics to Earth and other young planets is of critical importance for understanding the origin of Earth's volatiles, and for assessing the possible existence of exo-planets similar to Earth. Viewed from a cosmic perspective, Earth is a dry planet, yet its oceans are enriched in deuterium by a large factor relative to nebular hydrogen and analogous isotopic enrichments in atmospheric nitrogen and noble gases are also seen. Why is this so? What are the implications for Mars? For icy Worlds in our Planetary System? For the existence of Earth-like exoplanets? An exogenous (vs. outgassed) origin for Earth's atmosphere is implied, and intense debate on the relative contributions of comets and asteroids continues - renewed by fresh models for dynamical transport in the protoplanetary disk, by revelations on the nature and diversity of volatile and rocky material within comets, and by the discovery of ocean-like water in a comet from the Kuiper Belt (cf., Mumma & Charnley 2011). Assessing the creation of conditions favorable to the emergence and sustenance of life depends critically on knowledge of the nature of the impacting bodies. Active comets have long been grouped according to their orbital properties, and this has proven useful for identifying the reservoir from which a given comet emerged (OC, KB) (Levison 1996). However, it is now clear that icy bodies were scattered into each reservoir from a range of nebular distances, and the comet populations in today's reservoirs thus share origins that are (in part) common. Comets from the Oort Cloud and Kuiper Disk reservoirs should have diverse composition, resulting from strong gradients in temperature and chemistry in the proto-planetary disk, coupled with dynamical models of early radial transport and mixing with later dispersion of the final cometary nuclei into the long-term storage reservoirs. The inclusion of material from the natal interstellar cloud is probable

  8. Clinical features and hormonal profiles of cloprostenol-induced early abortions in heifers monitored by ultrasonography.

    Science.gov (United States)

    Lobago, Fikre; Gustafsson, Hans; Bekana, Merga; Beckers, Jean-François; Kindahl, Hans

    2006-11-23

    The present study describes the clinical features and plasma profiles of bovine pregnancy-associated glycoprotein 1 (bPAG1), the main metabolite of prostaglandin F2alpha (PG metabolite) and progesterone (P4) in heifers in which early abortions were induced. Early abortions were induced in four heifers with cloprostenol and monitored by ultrasonography. Blood samples were collected and the plasma were analyzed for bPAG 1, P4 and PG metabolite. The foetal heartbeat rates varied from 170-186 beats per minute for all foetuses up to the date of cloprostenol treatment. Foetal death was confirmed within two days after cloprostenol treatment. Prior to cloprostenol injection, blood plasma concentrations of bPAG1, PG metabolite and P4 varied from 8.4-40.0 ng/mL, 158-275 pmol/L and 20.7-46.9 nmol/L, respectively. After the foetus expelled, the plasma level of bPAG1 began to decrease but the decrease was small and gradual. The estimated half-life of bPAG1 was 1.8-6.6 days. The plasma level of the PG metabolite started to have short lasting peaks (above 300 pmol/L) within three hours after cloprostenol treatment. The plasma concentrations of P4 dropped sharply to less than 4 nmol/L after 24 hours of cloprostenol injection. The current findings indicated that after early closprostenol-induced foetal death, the plasma concentration of bPAG1 decreased gradually and showed a tendency of variation with the stages of pregnancy.

  9. Clinical features and hormonal profiles of cloprostenol-induced early abortions in heifers monitored by ultrasonography

    Directory of Open Access Journals (Sweden)

    Beckers Jean-François

    2006-11-01

    Full Text Available Abstract Background The present study describes the clinical features and plasma profiles of bovine pregnancy-associated glycoprotein 1 (bPAG1, the main metabolite of prostaglandin F2α (PG metabolite and progesterone (P4 in heifers in which early abortions were induced. Methods Early abortions were induced in four heifers with cloprostenol and monitored by ultrasonography. Blood samples were collected and the plasma were analyzed for bPAG 1, P4 and PG metabolite. Results The foetal heartbeat rates varied from 170–186 beats per minute for all foetuses up to the date of cloprostenol treatment. Foetal death was confirmed within two days after cloprostenol treatment. Prior to cloprostenol injection, blood plasma concentrations of bPAG1, PG metabolite and P4 varied from 8.4 – 40.0 ng/mL, 158 – 275 pmol/L and 20.7 – 46.9 nmol/L, respectively. After the foetus expelled, the plasma level of bPAG1 began to decrease but the decrease was small and gradual. The estimated half-life of bPAG1 was 1.8 – 6.6 days. The plasma level of the PG metabolite started to have short lasting peaks (above 300 pmol/L within three hours after cloprostenol treatment. The plasma concentrations of P4 dropped sharply to less than 4 nmol/L after 24 hours of cloprostenol injection. Conclusion The current findings indicated that after early closprostenol-induced foetal death, the plasma concentration of bPAG1 decreased gradually and showed a tendency of variation with the stages of pregnancy.

  10. Evaluating the forced oscillation technique in the detection of early smoking-induced respiratory changes.

    Science.gov (United States)

    Faria, Alvaro C D; Lopes, Agnaldo J; Jansen, José M; Melo, Pedro L

    2009-09-25

    Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD). The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system. The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases. Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects. Results from a group of 28 smokers with a tobacco consumption of 11.2 +/- 7.3 pack-years were compared with a control group formed by 28 healthy subjects using receiver operating characteristic (ROC) curves and a questionnaire as a gold standard. The early adverse effects of smoking were adequately detected by the absolute value of the respiratory impedance (Z4Hz), the intercept resistance (R0), and the respiratory system dynamic compliance (Crs, dyn). Z4Hz was the most accurate parameter (Se = 75%, Sp = 75%), followed by R0 and Crs, dyn. The performances of the FOT parameters in the detection of the early effects of smoking were higher than that of spirometry (p smoking-induced respiratory changes while these pathologic changes are still potentially reversible. These findings support the use of FOT as a versatile clinical diagnostic tool in aiding COPD prevention and treatment.

  11. The emergence of the "motoneuron concept": from the early 19th C to the beginning of the 20th C.

    Science.gov (United States)

    Clarac, François; Barbara, Jean-Gaël

    2011-08-29

    This article addresses the emergence of the "motoneuron concept," i.e., the idea that this cell had properties of particular advantage for its control of muscle activation. The motor function of the ventral roots was established early in the 19th C and the term "motor cell," (or "motor nerve cell") was introduced shortly thereafter by Albrecht von Kölliker and some other histologists. They knew that motor cells were among the neurons with the largest soma in vertebrates and for this reason they were, and remained for many decades, the best and most studied neuronal model. The work of clinicians like Guillaume Duchenne de Boulogne and Jean-Martin Charcot on motor degenerative syndromes began before a clear description of motor cells was available, because it was initially more difficult to establish whether the deficits of paralysis and muscle weakness were due to neuronal or muscular lesions. Next, the pioneering physiologist, Charles Sherrington, who was influenced greatly by the anatomical contributions and speculations of Santiago Ramón y Cajal, used the term, "motor neuron," rather than motor cell for the neuron that he considered was functionally "the final common path" for providing command signals to the musculature. In the early 20th C he proposed that activation of a motor neuron resulted from the sum of its various excitatory and inhibitory CNS inputs. The contraction of motor neuron to "motoneuron(e)" was put into common usage by John Fulton (among possibly others) in 1926. The motoneuron concept is still evolving with new discoveries on the horizon. 2011 Elsevier B.V. All rights reserved.

  12. Optical-fiber-based laser-induced breakdown spectroscopy for detection of early caries.

    Science.gov (United States)

    Sasazawa, Shuhei; Kakino, Satoko; Matsuura, Yuji

    2015-06-01

    A laser-induced breakdown spectroscopy (LIBS) system targeting for the in vivo analysis of tooth enamel is described. The system is planned to enable real-time analysis of teeth during laser dental treatment by utilizing a hollow optical fiber that transmits both Q-switched Nd:YAG laser light for LIBS and infrared Er:YAG laser light for tooth ablation. The sensitivity of caries detection was substantially improved by expanding the spectral region under analysis to ultraviolet (UV) light and by focusing on emission peaks of Zn in the UV region. Subsequently, early caries were distinguished from healthy teeth with accuracy rates above 80% in vitro.

  13. Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes

    DEFF Research Database (Denmark)

    Bartels, E D; Bang, C A; Nielsen, L B

    2009-01-01

    and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice. CONCLUSIONS: Our findings suggest that diet-induced type 2 diabetes causes early......BACKGROUND: Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia. MATERIALS AND METHODS: The effect of obesity and type 2 diabetes on the development...

  14. Optical-fiber-based laser-induced breakdown spectroscopy for detection of early caries

    Science.gov (United States)

    Sasazawa, Shuhei; Kakino, Satoko; Matsuura, Yuji

    2015-06-01

    A laser-induced breakdown spectroscopy (LIBS) system targeting for the in vivo analysis of tooth enamel is described. The system is planned to enable real-time analysis of teeth during laser dental treatment by utilizing a hollow optical fiber that transmits both Q-switched Nd:YAG laser light for LIBS and infrared Er:YAG laser light for tooth ablation. The sensitivity of caries detection was substantially improved by expanding the spectral region under analysis to ultraviolet (UV) light and by focusing on emission peaks of Zn in the UV region. Subsequently, early caries were distinguished from healthy teeth with accuracy rates above 80% in vitro.

  15. Angiogenic potential of early and late outgrowth endothelial progenitor cells is dependent on the time of emergence.

    Science.gov (United States)

    Minami, Yoshiyasu; Nakajima, Toshiaki; Ikutomi, Masayasu; Morita, Toshihiro; Komuro, Issei; Sata, Masataka; Sahara, Makoto

    2015-01-01

    Recent studies have suggested that late-outgrowth endothelial progenitor cells (EPCs) derived from human peripheral blood mononuclear cells (hPBMNCs) might have higher angiogenic potential than classically-defined early-outgrowth EPCs (EOCs). However, it still remains unclear which of "so-called" EPC subpopulations defined in a variety of ways has the highest angiogenic potential. We classified hPBMNC-derived EPC subpopulations by the time of their emergence in culture. EOCs were defined as attached cells on culture days 3-7. Late-outgrowth EPCs, defined as the cell forming colonies with cobblestone appearance since day 10, were further classified as follows: "moderate"-outgrowth EPCs (MOCs) emerging on days 10-16, "late"-outgrowth EPCs (LOCs) on days 17-23, and "very late"-outgrowth EPCs (VOCs) on days 24-30. Flow cytometry analyses showed the clear differences of hematopoietic/endothelial markers between EOC (CD31(+)VE-cadherin(-)CD34(-)CD14(+)CD45(+)) and LOC (CD31(+)VE-cadherin(+)CD34(+)CD14(-)CD45(-)). We found that LOCs had the highest proliferation and tube formation capabilities in vitro along with the highest expression of angiogenic genes including KDR and eNOS. To investigate the in vivo therapeutic efficacies, each EPC subpopulation was intravenously transplanted into immunocompromised mice (total 4 × 10(5) cells) after unilateral hindlimb ischemia surgery. The LOC-treated mice exhibited significantly-enhanced blood flow recovery (flow ratios of ischemic/non-ischemic leg: 0.99±0.02 [LOC group] versus 0.67 ± 0.07 to 0.78 ± 0.09 [other groups]; P capillary collateral formation in ischemic leg, which were attributable to their direct engraftment into host angiogenic vessels (approximately 10%) and paracrine effects. hPBMNC-derived late-outgrowth EPCs emerging on culture days 17-23 are superior to other EPC subpopulations with regard to therapeutic angiogenic potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Olanzapine-induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin.

    Science.gov (United States)

    Romo-Nava, Francisco; Buijs, Frederik N; Valdés-Tovar, Marcela; Benítez-King, Gloria; Basualdo, MariCarmen; Perusquía, Mercedes; Heinze, Gerhard; Escobar, Carolina; Buijs, Ruud M

    2017-05-01

    Second generation antipsychotics (SGA) are associated with adverse cardiometabolic side effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. As one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats. We evaluated the acute effects of olanzapine and melatonin in the biological clock, paraventricular nucleus and autonomic nervous system using immunohistochemistry, invasive cardiovascular measurements, and Western blot. Olanzapine induced c-Fos immunoreactivity in the SCN followed by the paraventricular nucleus and dorsal motor nucleus of the vagus indicating a potent induction of parasympathetic tone. The involvement of a SCN-parasympathetic neuronal pathway after olanzapine administration was further documented using cholera toxin-B retrograde tracing and vasoactive intestinal peptide immunohistochemistry. Olanzapine-induced decrease in blood pressure and heart rate confirmed this. Melatonin abolished olanzapine-induced SCN c-Fos immunoreactivity, including the parasympathetic pathway and cardiovascular effects while brain areas associated with olanzapine beneficial effects including the striatum, ventral tegmental area, and nucleus accumbens remained activated. In the SCN, olanzapine phosphorylated the GSK-3β, a regulator of clock activity, which melatonin prevented. Bilateral lesions of the SCN prevented the effects of olanzapine on parasympathetic activity. Collectively, results demonstrate the SCN as a key region mediating the early effects of olanzapine on cardiovascular function and show melatonin has opposing and potentially protective effects warranting additional investigation. © 2017

  17. Ultraviolet A-induced oxidation in cornea: Characterization of the early oxidation-related events.

    Science.gov (United States)

    Zinflou, Corinne; Rochette, Patrick J

    2017-07-01

    Exposure to sunlight ultraviolet-A (UVA), the main component of solar UV reaching the eyes, is suspected to play an important part in the onset of ocular pathologies. UVA primary biological deleterious effects arise from the photo-induction of oxidative stress in cells. However, the molecular bases linking UVA-induced oxidation to UVA toxicity in eyes remain poorly understood, especially with regards to the cornea. To shed some light on this issue, we have investigated the susceptibility and response potential of the different corneal cellular layers (epithelium, stroma and endothelium) to UVA-induced oxidation. We have monitored UVA-induced immediate effects on cellular redox balance, on mitochondrial membrane potential, on 8-Hydroxy-2'-deoxyguanosine (8-OHdG) accumulation in cellular DNA and on S-glutathionylated proteins (PSSG) levels along whole rabbit corneas. Higher redox imbalance was observed in the posterior part of the cornea following irradiation. Conversely, UVA-altered mitochondrial membrane potentials were observed only in anterior portions of the cornea. UVA-induced 8-OHdG were found in nuclear DNA of epithelia, while they were found in both nuclear and mitochondrial DNA in stromal and endothelial cells. Finally, significantly higher levels of cytosolic PSSG were measured in epithelia and endothelia immediately after UVA exposure, but not in stromas. Taken together, our findings indicate that while corneal epithelial cells are subjected to important modifications in response to UVA exposure, they efficiently limit the early manifestations of UVA-induced toxicity. On the other hand, the corneal endothelium is more susceptible to UVA-induced oxidation-related toxicity. Copyright © 2017. Published by Elsevier Inc.

  18. Treatment of early pregnancy failure: does induced abortion training affect later practices?

    Science.gov (United States)

    Dalton, Vanessa K; Harris, Lisa H; Bell, Jason D; Schulkin, Jay; Steinauer, Jodi; Zochowski, Melissa; Fendrick, A Mark

    2011-06-01

    The objective of the study was to examine the relationship between induced abortion training and views toward, and use of, office uterine evacuation and misoprostol in early pregnancy failure (EPF) care. We surveyed 308 obstetrician-gynecologists on their knowledge and attitudes toward treatment options for EPF and previous training in office-based uterine evacuation. Sixty-seven percent of respondents reported training in office uterine evacuation, and 20.3% reported induced abortion training. Induced abortion training was associated with strongly positive views toward both office-based uterine evacuation and misoprostol as treatment for EPF compared with those with office uterine evacuation training in other settings (odds ratio [OR], 2.64; P abortion training was associated with the use of office uterine evacuation for EPF treatment compared with those with office evacuation training in other settings (OR, 2.90; P = .004). Training experiences, especially induced abortion training, are associated with the use of office uterine evacuation for EPF. Copyright © 2011 Mosby, Inc. All rights reserved.

  19. Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage in Adult Rats.

    Science.gov (United States)

    Dorfman, Damián; Aranda, Marcos L; Rosenstein, Ruth E

    2015-01-01

    Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm) optic nerve (ON) could be the first structural change of the visual pathway in streptozotocin (STZ)-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE) or remained in a standard environment (SE) for 6 weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine blue staining and phosphorylated neurofilament heavy immunoreactivity), microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1) immunoreactivity), astrocyte reactivity (glial fibrillary acid protein-immunostaining), myelin (myelin basic protein immunoreactivity), ultrastructure, and brain derived neurotrophic factor (BDNF) levels were assessed in non-diabetic and diabetic animals housed in SE or EE. No differences in retinal morphology or retinal ganglion cell number were observed among groups. EE housing which did not affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the anterograde transport from the retina to the superior colliculus, ON axon number, and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as well as ultrastructural myelin alterations in the ON distal portion at early stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels induced by experimental diabetes. These results suggest that EE induced neuroprotection in the diabetic visual pathway.

  20. Effect of Early Pelvic Binder Use in the Emergency Management of Suspected Pelvic Trauma: A Retrospective Cohort Study

    Science.gov (United States)

    Hsu, Sheng-Der; Chen, Cheng-Jueng; Chou, Yu-Ching; Wang, Sheng-Hao; Chan, De-Chuan

    2017-01-01

    Background: We aimed to evaluate the effect of early pelvic binder use in the emergency management of suspected pelvic trauma, compared with the conventional stepwise approach. Methods: We enrolled trauma patients with initial stabilization using a pelvic binder when suspecting pelvic injury. The inclusion criteria were traumatic injury requiring a trauma team and at least one of the following: a loss of consciousness or a Glasgow coma score (GCS) of pelvic injury. Various parameters, including gender, age, mechanism of injury, GCS, mortality, hospital stay, initial vital signs, revised trauma score, injury severity score, and outcome, were assessed and compared with historical controls. Results: A total of 204 patients with high-energy multiple-trauma from a single level I trauma center in North Taiwan were enrolled in the study from August 2013 to July 2014. The two group baseline patient characteristics were all collected and compared. The trauma patients with suspected pelvic fractures initially stabilized with a pelvic binder had shorter hospital and intensive care unit (ICU) stays. The study group achieved statistically significantly improved survival and lower mean blood transfusion volume and mortality rate, although they were more severe in the trauma score. Conclusions: We recommend prompt pelvic binder use for suspected pelvic injury before definitive imaging is available, as a cervical spine collar is used to protect the cervical spine from further injury prior to definitive identification and characterization of an injury. PMID:29023379

  1. Early childhood caries-related visits to emergency departments and ambulatory surgery facilities and associated charges in New York state.

    Science.gov (United States)

    Nagarkar, Sanket R; Kumar, Jayanth V; Moss, Mark E

    2012-01-01

    The authors assessed the extent of early childhood caries- (ECC-) related visits to emergency departments (EDs) and ambulatory surgery facilities (ASFs) in children younger than 6 years and associated treatment charges in New York state from 2004 through 2008. The authors obtained data from the New York state's Statewide Planning and Research Cooperative System (Albany) and calculated descriptive statistics and rates according to selected indicators, as well as total and average per-visit treatment charges. From 2004 through 2008, the number of ECC-related visits to EDs and ASFs increased by 349 and 1,039, respectively. Most ECC-related visits were to ASFs. The total annual treatment charges increased from $18.5 million to $31.3 million from 2004 to 2008, and average per-visit charges increased from $4,237 to $5,501 during the same period. ECC-related visits to EDs and ASFs by children younger than 6 years and the associated treatment charges increased substantially from 2004 through 2008 in New York state. Practice Implications. Dental professionals need to determine the reasons parents seek dental care for their children in EDs and ASFs and effective strategies for preventing ECC to avoid the subsequent need for seeking dental care in EDs and ASFs.

  2. Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department.

    Science.gov (United States)

    Viale, Pierluigi; Tedeschi, Sara; Scudeller, Luigia; Attard, Luciano; Badia, Lorenzo; Bartoletti, Michele; Cascavilla, Alessandra; Cristini, Francesco; Dentale, Nicola; Fasulo, Giovanni; Legnani, Giorgio; Trapani, Filippo; Tumietto, Fabio; Verucchi, Gabriella; Virgili, Giulio; Berlingeri, Andrea; Ambretti, Simone; De Molo, Chiara; Brizi, Mara; Cavazza, Mario; Giannella, Maddalena

    2017-10-15

    The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. Neural correlates of multisensory reliability and perceptual weights emerge at early latencies during audio-visual integration.

    Science.gov (United States)

    Boyle, Stephanie C; Kayser, Stephanie J; Kayser, Christoph

    2017-11-01

    To make accurate perceptual estimates, observers must take the reliability of sensory information into account. Despite many behavioural studies showing that subjects weight individual sensory cues in proportion to their reliabilities, it is still unclear when during a trial neuronal responses are modulated by the reliability of sensory information or when they reflect the perceptual weights attributed to each sensory input. We investigated these questions using a combination of psychophysics, EEG-based neuroimaging and single-trial decoding. Our results show that the weighted integration of sensory information in the brain is a dynamic process; effects of sensory reliability on task-relevant EEG components were evident 84 ms after stimulus onset, while neural correlates of perceptual weights emerged 120 ms after stimulus onset. These neural processes had different underlying sources, arising from sensory and parietal regions, respectively. Together these results reveal the temporal dynamics of perceptual and neural audio-visual integration and support the notion of temporally early and functionally specific multisensory processes in the brain. © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

    Science.gov (United States)

    Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

    2018-03-01

    Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Net Late Holocene emergence despite earthquake-induced submergence, south-central Chile

    Science.gov (United States)

    Atwater, B.F.; Nunez, H.J.; Vita-Finzi, C.

    1992-01-01

    Intertidal deposits show net Late Holocene emergence at three sites along the Pacific coast near Maulli??n and Carelmapu, Chile (latitude 41.6-41.7??S.). The maximum amount of net emergence is ca. 1 m in the past 1500 years and ca. 2 1 2 m in the past 4000 years. Emergence probably would have prevailed at a fourth site near Maulli??n were the site not underlain by easily compacted deposits; this site shows slight (earthquake in 1960, and two of the sites show evidence for earlier submergence events of Late Holocene age. The net emergence is probably due to some combination of cyclic uplift from elastic strain accumulation between earthquakes and monotonic uplift from postglacial loading of the Pacific Ocean floor. The small amount of the net emergence shows that neotectonics has had little net impact on Holocene relative sea level in part of the focal region of the largest earthquake recorded by seismograph. ?? 1992.

  6. Expression of immediate-early genes in the dorsal cochlear nucleus in salicylate-induced tinnitus.

    Science.gov (United States)

    Hu, Shou-Sen; Mei, Ling; Chen, Jian-Yong; Huang, Zhi-Wu; Wu, Hao

    2016-02-01

    Spontaneous neuronal activity in dorsal cochlear nucleus (DCN) may be involved in the physiological processes underlying salicylate-induced tinnitus. As a neuronal activity marker, immediate-early gene (IEG) expression, especially activity-dependent cytoskeletal protein (Arc/Arg3.1) and the early growth response gene-1 (Egr-1), appears to be highly correlated with sensory-evoked neuronal activity. However, their relationships with tinnitus induced by salicylate have rarely been reported in the DCN. In this study, we assessed the effect of acute and chronic salicylate treatment on the expression of N-methyl D-aspartate receptor subunit 2B (NR2B), Arg3.1, and Egr-1. We also observed ultrastructural alterations in the DCN synapses in an animal model of tinnitus. Levels of mRNA and protein expression of NR2B and Arg3.1 were increased in rats that were chronically administered salicylate (200 mg/kg, twice daily for 3, 7, or 14 days). These levels returned to baseline 14 days after cessation of treatment. However, no significant changes were observed in Egr-1 gene expression in any groups. Furthermore, rats subjected to long-term salicylate administration showed more presynaptic vesicles, thicker and longer postsynaptic densities, and increased synaptic interface curvature. Alterations of Arg3.1 and NR2B may be responsible for the changes in the synaptic ultrastructure. These changes confirm that salicylate can cause neural plasticity changes at the DCN level.

  7. Experimental study on early detection of alloxan-induced pulmonary injury by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Awai, Kazuo; Fukuda, Hiroshi; Nakamura, Susumu; Fujikawa, Koichi; Utsumi, Toshio; Kajima, Toshio; Azuma, Kazuyoshi; Ito, Katsuhide.

    1995-01-01

    We studied the early detection of alloxan-induced pulmonary injury by magnetic resonance imaging in vivo. Permeability edema was induced in ten rats by intravenous injection of alloxan at 100 mg/Kg. T1-and T2-weighted images were acquired in five rats every 30 min for 120 min after alloxan injection. Five rats served as controls. The rats were sacrificed immediately after imaging and examined microscopically. CT images were also acquired in five rats every 30 min for 120 min after alloxan injection. Five rats served as controls. The rats were sacrificed immediately after imaging, and the wet-to-dry ratio of the lung was measured. In T1-weighted images, relative signal intensity from the lung with permeability edema rose from 30 min to 120 min, and was greater than that from normal lung every time. In T2-weighted images, there was no statistically significant difference in relative signal intensity of the lung between permeability edema and the control during 120 min. In CT images, there was also no statistically significant difference in lung density between permeability edema and the control during 120 min. There was no statistically significant difference in the wet-to-dry lung ratio between edematous lung and normal lung. In histological study, mild congestion and interstitial edema were observed in edematous lung. These results suggest the potential capability of MR imaging in detecting the early phase of permeability pulmonary edema. (author)

  8. Early onset imatinib mesylate-induced hepatotoxicity in a patient with gastrointestinal stromal tumors.

    Science.gov (United States)

    Yachoui, Ralph

    2014-01-01

    Imatinib mesylate is used for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs). It has been associated with severe hepatotoxicity, which may lead to liver failure and death. Few cases of imatinib mesylate-induced liver failure have been reported; most of them were observed in patients treated for chronic myeloid leukemia. To date, 2 cases were reported in patients treated for GISTs. Elevation of liver function tests is usually observed during the first 2-3 months after the initiation of therapy. We report a 46-year-old woman with advanced GISTs who developed hepatotoxicity 11 days after the initiation of imatinib therapy. Before therapy with imatinib, her liver function tests were normal. She had no known risk factors for viral or alcoholic liver disease. Imatinib was her only regular medication, and she had not used acetaminophen or over-the-counter medications. Her serologic studies for hepatitis were all negative. One week after imatinib discontinuation, liver function tests improved significantly. The present report confirms the possibility of early onset imatinib mesylate-induced liver failure in patients treated for GISTs. Surveillance of liver function tests should start early after the initiation of treatment and during all the duration of therapy.

  9. Brodifacoum induces early hemoglobinuria and late hematuria in rats: novel rapid biomarkers of poisoning.

    Science.gov (United States)

    Ware, Kyle M; Feinstein, Douglas L; Rubinstein, Israel; Weinberg, Guy; Rovin, Brad H; Hebert, Lee; Muni, Navin; Cianciolo, Rachel E; Satoskar, Anjali A; Nadasdy, Tibor; Brodsky, Sergey V

    2015-01-01

    Brodifacoum (BDF) is a superwarfarin that is used primarily as a rodenticide. There have been increasing numbers of reports of human cases of accidental or intentional BDF ingestion with high mortality rate. Its broad availability and high lethality suggest that BDF should be considered a potential chemical threat. Currently, there is no biomarker for early detection of BDF ingestion in humans; patients typically present with severe coagulopathy. Since we demonstrated earlier that warfarin can induce acute kidney injury with hematuria, we tested whether BDF would also lead to change in urinary biomarkers. BDF was administered to Sprague Dawley rats via oral gavage. N-acetylcysteine (NAC) was given per os in drinking water 24 h prior to BDF. Urinalysis was performed at different times after BDF administration. Anticoagulation and serum creatinine levels were analyzed in the blood. We observed that within a few hours the animals developed BDF-dose-dependent transient hemoglobinuria, which ceased within 24 h. This was accompanied by a transient decrease in hematocrit, gross hemolysis and an increase in free hemoglobin in the serum. At later times, animals developed true hematuria with red blood cells in the urine, which was associated with BDF anticoagulation. NAC prevented early hemoglobinuria, but not late hematuria associated with BDF. We propose that transient early hemoglobinuria (associated with oxidative stress) with consecutive late hematuria (associated with anticoagulation) are novel biomarkers of BDF poisoning, and they can be used in clinical setting or in mass casualty with BDF to identify poisoned patients. © 2015 S. Karger AG, Basel.

  10. High-frequency audiometry: A means for early diagnosis of noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Amir H Mehrparvar

    2011-01-01

    Full Text Available Noise-induced hearing loss (NIHL, an irreversible disorder, is a common problem in industrial settings. Early diagnosis of NIHL can help prevent the progression of hearing loss, especially in speech frequencies. For early diagnosis of NIHL, audiometry is performed routinely in conventional frequencies. We designed this study to compare the effect of noise on high-frequency audiometry (HFA and conventional audiometry. In a historical cohort study, we compared hearing threshold and prevalence of hearing loss in conventional and high frequencies of audiometry among textile workers divided into two groups: With and without exposure to noise more than 85 dB. The highest hearing threshold was observed at 4000 Hz, 6000 Hz and 16000 Hz in conventional right ear audiometry, conventional left ear audiometry and HFA in each ear, respectively. The hearing threshold was significantly higher at 16000 Hz compared to 4000. Hearing loss was more common in HFA than conventional audiometry. HFA is more sensitive to detect NIHL than conventional audiometry. It can be useful for early diagnosis of hearing sensitivity to noise, and thus preventing hearing loss in lower frequencies especially speech frequencies.

  11. PEX11β induces peroxisomal gene expression and alters peroxisome number during early Xenopus laevis development

    Directory of Open Access Journals (Sweden)

    Damjanovski Sashko

    2011-04-01

    Full Text Available Abstract Background Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that de novo peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although de novo biogenesis and divisions are likely important mechanisms, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as frogs where large embryonic yolk and fatty acid stores must be quickly metabolized, and resulting reactive oxygen species eliminated. Here we elucidate the role of Pex11β in regulating peroxisomal gene expression and number in Xenopus laevis embryogenesis. Results Microinjecting haemagglutinin (HA tagged Pex11β in early embryos resulted in increased RNA levels for peroxisome related genes PMP70 and catalase at developmental stages 10 and 20, versus uninjected embryos. Catalase and PMP70 proteins were found in punctate structures at stage 20 in control embryos, whereas the injection of ectopic HA-Pex11β induced their earlier localization in punctate structures at stage 10. Furthermore, the peroxisomal marker GFP-SKL, which was found localized as peroxisome-like structures at stage 20, was similarly found at stage 10 when co-microinjected with HA-Pex11β. Conclusions Overexpressed Pex11β altered peroxisomal gene levels and induced the early formation of peroxisomes-like structures during development, both of which demonstrate that Pex11β may be a key regulator of peroxisome number in early Xenopus embryos.

  12. Early Treatment of radiation-Induced Heart Damage in Rats by Caffeic acid phenethyl Ester

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Mansour, H. H.

    2012-12-01

    The study designed to determine the therapeutic effect of caffeic acid phenethyl ester (CAPE) in minimising radiation-induced injuries in rats. Rats were exposed to 7 Gy γ-rays, 30 minutes later; rats were injected with CAPE (10μmol/ kg body, i.p.) for 7 consecutive days. Rats were sacrificed at 8 and 15 days after starting the experiment. Gamma-irradiation induced significant increase in malonaldehyde (MDA) level and xanthine oxidase (XO) and adenosine deaminase (ADA) activities, and significant decrease in total nitrate/nitrate (NO (x)) level and glutathione peroxidise (Gpx), superoxide dismutase (SOD)and catalase (CAT) activities in heart tissue and augmented activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate transaminase (AST) in serum. Irradiated rats early treated with CAPE showed significant decrease in MDA, XO and ADA and significant increase in group. Cardiac enzymes were restored. Conclusion, CAPE could exhibits curable effect on gamma irradiation-induced cardiac-oxidative impairment in rats. (Author)

  13. PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.

    Science.gov (United States)

    Orth, P; Cucchiarini, M; Wagenpfeil, S; Menger, M D; Madry, H

    2014-06-01

    To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. [Interventional emergency embolization for severe pelvic ring fractures with arterial bleeding. Integration into the early clinical treatment algorithm].

    Science.gov (United States)

    Westhoff, J; Laurer, H; Wutzler, S; Wyen, H; Mack, M; Maier, B; Marzi, I

    2008-10-01

    Presentation of our own experiences and results of an early clinical algorithm for treatment integrating emergency embolization (TAE) in cases of unstable pelvic ring fractures with arterial bleeding. Consecutive patient series from April 2002 to December 2006 at a level 1 trauma center. The data of the online shock room documentation (Traumawatch) of patients with a pelvic fracture and arterial bleeding detected on multislice computed tomography (MSCT) were examined for the following parameters: demographic data, injury mechanism, fracture classification according to Tile/AO and severity of the pelvic injury assessed with the Abbreviated Injury Score (AIS), accompanying injuries with elevation of the cumulative injury severity according to the Injury Severity Score (ISS), physiological admission parameters (circulatory parameters and initial Hb value) as well as transfusion requirement during treatment in the shock room, time until embolization, duration of embolization, and source of bleeding. Of a total of 162 patients, arterial bleeding was detected in 21 patients by contrast medium extravasation on MSCT, 12 of whom were men and 9 women with an average age of 45 (14-80) years. The mechanism of injury was high energy trauma in all cases. In 33% it involved type B pelvic fractures and in 67% type C fractures with an average AIS pelvis of 4.4 points (3-5) and a total severity of injury with the ISS of 37 points (21-66). Upon admission 47.6% presented hemodynamic instability with an average Hb value of 7.8 g/dl (3.2-12.4) and an average transfusion requirement of 6 red blood cell units (4-13). The time until the TAE was started was on average 62 min (25-115) with a duration period of the TAE of 25 min (15-67). Branches of the internal iliac artery were identified as the sole source of bleeding. The success rate of TAE amounted to over 90%. Interventional TAE represents an effective as well as a fast procedure for hemostasis of arterial bleeding detected on MSCT in

  15. Potential early predictors for outcomes of experimental hemorrhagic shock induced by uncontrolled internal bleeding in rats.

    Directory of Open Access Journals (Sweden)

    Zaid A Abassi

    Full Text Available Uncontrolled hemorrhage, resulting from traumatic injuries, continues to be the leading cause of death in civilian and military environments. Hemorrhagic deaths usually occur within the first 6 hours of admission to hospital; therefore, early prehospital identification of patients who are at risk for developing shock may improve survival. The aims of the current study were: 1. To establish and characterize a unique model of uncontrolled internal hemorrhage induced by massive renal injury (MRI, of different degrees (20-35% unilateral nephrectomy in rats, 2. To identify early biomarkers those best predict the outcome of severe internal hemorrhage. For this purpose, male Sprague Dawley rats were anesthetized and cannulas were inserted into the trachea and carotid artery. After abdominal laparotomy, the lower pole of the kidney was excised. During 120 minutes, hematocrit, pO2, pCO2, base excess, potassium, lactate and glucose were measured from blood samples, and mean arterial pressure (MAP was measured through arterial tracing. After 120 minutes, blood loss was determined. Statistical prediction models of mortality and amount of blood loss were performed. In this model, the lowest blood loss and mortality rate were observed in the group with 20% nephrectomy. Escalation of the extent of nephrectomy to 25% and 30% significantly increased blood loss and mortality rate. Two phases of hemodynamic and biochemical response to MRI were noticed: the primary phase, occurring during the first 15 minutes after injury, and the secondary phase, beginning 30 minutes after the induction of bleeding. A Significant correlation between early blood loss and mean arterial pressure (MAP decrements and survival were noted. Our data also indicate that prediction of outcome was attainable in the very early stages of blood loss, over the first 15 minutes after the injury, and that blood loss and MAP were the strongest predictors of mortality.

  16. Emerging roles of hypoxia-inducible factors and reactive oxygen species in cancer and pluripotent stem cells

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    Shigeo Saito

    2015-06-01

    Full Text Available Eukaryotic organisms require oxygen homeostasis to maintain proper cellular function for survival. During conditions of low oxygen tension (hypoxia, cells activate the transcription of genes that induce an adaptive response, which supplies oxygen to tissues. Hypoxia and hypoxia-inducible factors (HIFs may contribute to the maintenance of putative cancer stem cells, which can continue self-renewal indefinitely and express stemness genes in hypoxic stress environments (stem cell niches. Reactive oxygen species (ROS have long been recognized as toxic by-products of aerobic metabolism that are harmful to living cells, leading to DNA damage, senescence, or cell death. HIFs may promote a cancer stem cell state, whereas the loss of HIFs induces the production of cellular ROS and activation of proteins p53 and p16Ink4a, which lead to tumor cell death and senescence. ROS seem to inhibit HIF regulation in cancer cells. By contrast, controversial data have suggested that hypoxia increases the generation of ROS, which prevents hydroxylation of HIF proteins by inducing their transcription as negative feedback. Moreover, hypoxic conditions enhance the generation of induced pluripotent stem cells (iPSCs. During reprogramming of somatic cells into a PSC state, cells attain a metabolic state typically observed in embryonic stem cells (ESCs. ESCs and iPSCs share similar bioenergetic metabolisms, including decreased mitochondrial number and activity, and induced anaerobic glycolysis. This review discusses the current knowledge regarding the emerging roles of ROS homeostasis in cellular reprogramming and the implications of hypoxic regulation in cancer development.

  17. Effects of emergence time and early social rearing environment on behaviour of Atlantic salmon: consequences for juvenile fitness and smolt migration.

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    Martin H Larsen

    Full Text Available Consistent individual differences in behaviour have been well documented in a variety of animal taxa, but surprisingly little is known about the fitness and life-history consequences of such individual variation. In wild salmonids, the timing of fry emergence from gravel spawning nests has been suggested to be coupled with individual behavioural traits. Here, we further investigate the link between timing of spawning nest emergence and behaviour of Atlantic salmon (Salmo salar, test effects of social rearing environment on behavioural traits in fish with different emergence times, and assess whether behavioural traits measured in the laboratory predict growth, survival, and migration status in the wild. Atlantic salmon fry were sorted with respect to emergence time from artificial spawning nest into three groups: early, intermediate, and late. These emergence groups were hatchery-reared separately or in co-culture for four months to test effects of social rearing environment on behavioural traits. Twenty fish from each of the six treatment groups were then subjected to three individual-based behavioural tests: basal locomotor activity, boldness, and escape response. Following behavioural characterization, the fish were released into a near-natural experimental stream. Results showed differences in escape behaviour between emergence groups in a net restraining test, but the social rearing environment did not affect individual behavioural expression. Emergence time and social environment had no significant effects on survival, growth, and migration status in the stream, although migration propensity was 1.4 to 1.9 times higher for early emerging individuals that were reared separately. In addition, despite individuals showing considerable variation in behaviour across treatment groups, this was not translated into differences in growth, survival, and migration status. Hence, our study adds to the view that fitness (i.e., growth and survival and

  18. Using European travellers as an early alert to detect emerging pathogens in countries with limited laboratory resources

    Directory of Open Access Journals (Sweden)

    Grais Rebecca

    2007-01-01

    Full Text Available Abstract Background The volume, extent and speed of travel have dramatically increased in the past decades, providing the potential for an infectious disease to spread through the transportation network. By collecting information on the suspected place of infection, existing surveillance systems in industrialized countries may provide timely information for areas of the world without adequate surveillance currently in place. We present the results of a case study using reported cases of Shigella dysenteriae serotype 1 (Sd1 in European travellers to detect "events" of Sd1, related to either epidemic cases or endemic cases in developing countries. Methods We identified papers from a Medline search for reported events of Sd1 from 1940 to 2002. We requested data on shigella infections reported to the responsible surveillance entities in 17 European countries. Reports of Sd1 from the published literature were then compared with Sd1 notified cases among European travellers from 1990 to 2002. Results Prior to a large epidemic in 1999–2000, no cases of Sd1 had been identified in West Africa. However, if travellers had been used as an early warning, Sd1 could have been identified in this region as earlier as 1992. Conclusion This project demonstrates that tracking diseases in European travellers could be used to detect emerging disease in developing countries. This approach should be further tested with a view to the continuous improvement of national health surveillance systems and existing European networks, and may play a significant role in aiding the international public health community to improve infectious disease control.

  19. Early life hormetic treatments decrease irradiation-induced oxidative damage, increase longevity, and enhance sexual performance during old age in the Caribbean fruit fly.

    Directory of Open Access Journals (Sweden)

    Giancarlo López-Martínez

    Full Text Available Early life events can have dramatic consequences on performance later in life. Exposure to stressors at a young age affects development, the rate of aging, risk of disease, and overall lifespan. In spite of this, mild stress exposure early in life can have beneficial effects on performance later in life. These positive effects of mild stress are referred to as physiological conditioning hormesis. In our current study we used anoxia conditioning hormesis as a pretreatment to reduce oxidative stress and improve organismal performance, lifespan, and healthspan of Caribbean fruit flies. We used gamma irradiation to induce mild oxidative damage in a low-dose experiment, and massive oxidative damage in a separate high-dose experiment, in pharate adult fruit flies just prior to adult emergence. Irradiation-induced oxidative stress leads to reduced adult emergence, flight ability, mating performance, and lifespan. We used a hormetic approach, one hour of exposure to anoxia plus irradiation in anoxia, to lower post-irradiation oxidative damage. We have previously shown that this anoxic-conditioning treatment elevates total antioxidant capacity and lowers post-irradiation oxidative damage to lipids and proteins. In this study, conditioned flies had lower mortality rates and longer lifespan compared to those irradiated without hormetic conditioning. As a metric of healthspan, we tracked mating both at a young age (10 d and old age (30 d. We found that anoxia-conditioned male flies were more competitive at young ages when compared to unconditioned irradiation stressed male flies, and that the positive effects of anoxic conditioning hormesis on mating success were even more pronounced in older males. Our data shows that physiological conditioning hormesis at a young age, not only improves immediate metrics of organismal performance (emergence, flight, mating, but the beneficial effects also carry into old age by reducing late life oxidative damage and

  20. Early life hormetic treatments decrease irradiation-induced oxidative damage, increase longevity, and enhance sexual performance during old age in the Caribbean fruit fly

    International Nuclear Information System (INIS)

    López-Martínez, Giancarlo; Hahn, Daniel A.

    2014-01-01

    Early life events can have dramatic consequences on performance later in life. Exposure to stressors at a young age affects development, the rate of aging, risk of disease, and overall lifespan. In spite of this, mild stress exposure early in life can have beneficial effects on performance later in life. These positive effects of mild stress are referred to as physiological conditioning hormesis. In our current study we used anoxia conditioning hormesis as a pretreatment to reduce oxidative stress and improve organismal performance, lifespan, and healthspan of Caribbean fruit flies. We used gamma irradiation to induce mild oxidative damage in a low-dose experiment, and massive oxidative damage in a separate high-dose experiment, in pharate adult fruit flies just prior to adult emergence. Irradiation-induced oxidative stress leads to reduced adult emergence, flight ability, mating performance, and lifespan. We used a hormetic approach, one hour of exposure to anoxia plus irradiation in anoxia, to lower post-irradiation oxidative damage. We have previously shown that this anoxic-conditioning treatment elevates total antioxidant capacity and lowers post-irradiation oxidative damage to lipids and proteins. In this study, conditioned flies had lower mortality rates and longer lifespan compared to those irradiated without hormetic conditioning. As a metric of healthspan, we tracked mating both at a young age (10 d) and old age (30 d). We found that anoxia-conditioned male flies were more competitive at young ages when compared to unconditioned irradiation stressed male flies, and that the positive effects of anoxic conditioning hormesis on mating success were even more pronounced in older males. Our data shows that physiological conditioning hormesis at a young age, not only improves immediate metrics of organismal performance (emergence, flight, mating), but the beneficial effects also carry into old age by reducing late life oxidative damage and improving lifespan and

  1. Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage in Adult Rats.

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    Damián Dorfman

    Full Text Available Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm optic nerve (ON could be the first structural change of the visual pathway in streptozotocin (STZ-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE or remained in a standard environment (SE for 6 weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine blue staining and phosphorylated neurofilament heavy immunoreactivity, microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1 immunoreactivity, astrocyte reactivity (glial fibrillary acid protein-immunostaining, myelin (myelin basic protein immunoreactivity, ultrastructure, and brain derived neurotrophic factor (BDNF levels were assessed in non-diabetic and diabetic animals housed in SE or EE. No differences in retinal morphology or retinal ganglion cell number were observed among groups. EE housing which did not affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the anterograde transport from the retina to the superior colliculus, ON axon number, and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as well as ultrastructural myelin alterations in the ON distal portion at early stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels induced by experimental diabetes. These results suggest that EE induced neuroprotection in the diabetic visual pathway.

  2. Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

    Science.gov (United States)

    Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

    2017-07-01

    Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

  3. Early Onset Dapsone-induced Photosensitive Dermatitis: A Rare Side Effect of a Common Drug.

    Science.gov (United States)

    Karjigi, S; Murthy, S C; Kallappa, H; Kusuma, M R; Reddy, Y N K

    2015-01-01

    Dapsone, a potent anti-inflammatory compound, is mainly used in the treatment of leprosy, dermatitis herpetiformis, erythema elevatum diutinum and other dermatoses. Cutaneous adverse reactions range from acneiform eruptions to toxic epidermal necrolysis. A 30-year-old, married women who was treated with paucibacillary multi drug therapy, developed itchy skin lesions over the both forearms, 'V ' area of the neck and upper back after one week of the drug administration which worsened on exposure to sunlights. A clinical diagnosis of dapsone-induced photosensitive dermatitis was confirmed by histopathology and recurrence of symptoms and signs after re-exposure to the drug. Photosensitivity due to dapsone is rare and very few reports are available in the literature. Our patient had an unusually early onset compared to the previously reported cases.

  4. Early synaptic dysfunction induced by alpha-synuclein in a rat model of Parkinson's disease

    DEFF Research Database (Denmark)

    Phan, Jenny-Ann; Stokholm, Kathrine; Zareba-Paslawska, Justyna

    2017-01-01

    Evidence suggests that synapses are affected first in Parkinson’s disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats...... that overexpress human α-synuclein by local injection of viral-vectors in midbrain. We aimed to achieve α-synuclein levels sufficient to induce terminal pathology without significant loss of nigral neurons. We tested synaptic disruption in vivo by analyzing motor defects and binding of a positron emission...... tomography (PET) radioligand to the vesicular monoamine transporter 2, (VMAT2), [11C]dihydrotetrabenazine (DTBZ). Animals overexpressing α-synuclein had progressive motor impairment and, 12 weeks post-surgery, showed asymmetric in vivo striatal DTBZ binding. The PET images matched ligand binding in post...

  5. Direct evidence that radiation induced micronuclei of early embryos require a mitosis for expression

    International Nuclear Information System (INIS)

    Mueller, W.U.; Schlusen, I.; Streffer, C.

    1991-01-01

    The naturally synchronous development of early mouse embryos was exploited to address the question, whether micronuclei require a mitosis for expression or whether they can be expressed in the same cell cycle, in which exposure to X-rays or caffeine took place. Experiments with 2-cell and with 4-cell embryos showed that micronulcei are expressed only if a mitosis is completed. There was no indication, even after doses up to 20 Gy, that micronuclei can be expressed before the mitosis was reached, which followed exposure. Furthermore, no nuclear fragmentation pointing to apoptosis could be detected in the cycle, in which cells were exposed. The same results were obtained when caffeine (5 mM) was used as micronucleus inducing agent. (orig.)

  6. Early prediction of polymyxin-induced nephrotoxicity with next-generation urinary kidney injury biomarkers.

    Science.gov (United States)

    Keirstead, Natalie D; Wagoner, Matthew P; Bentley, Patricia; Blais, Marie; Brown, Crystal; Cheatham, Letitia; Ciaccio, Paul; Dragan, Yvonne; Ferguson, Douglas; Fikes, Jim; Galvin, Melanie; Gupta, Anshul; Hale, Michael; Johnson, Nakpangi; Luo, Wenli; McGrath, Frank; Pietras, Mark; Price, Sally; Sathe, Abhishek G; Sasaki, Jennifer C; Snow, Debra; Walsky, Robert L; Kern, Gunther

    2014-02-01

    Despite six decades of clinical experience with the polymyxin class of antibiotics, their dose-limiting nephrotoxicity remains difficult to predict due to a paucity of sensitive biomarkers. Here, we evaluate the performance of standard of care and next-generation biomarkers of renal injury in the detection and monitoring of polymyxin-induced acute kidney injury in male Han Wistar rats using colistin (polymyxin E) and a polymyxin B (PMB) derivative with reduced nephrotoxicity, PMB nonapeptide (PMBN). This study provides the first histopathological and biomarker analysis of PMBN, an important test of the hypothesis that fatty acid modifications and charge reductions in polymyxins can reduce their nephrotoxicity. The results indicate that alterations in a panel of urinary kidney injury biomarkers can be used to monitor histopathological injury, with Kim-1 and α-GST emerging as the most sensitive biomarkers outperforming clinical standards of care, serum or plasma creatinine and blood urea nitrogen. To enable the prediction of polymyxin-induced nephrotoxicity, an in vitro cytotoxicity assay was employed using human proximal tubule epithelial cells (HK-2). Cytotoxicity data in these HK-2 cells correlated with the renal toxicity detected via safety biomarker data and histopathological evaluation, suggesting that in vitro and in vivo methods can be incorporated within a screening cascade to prioritize polymyxin class analogs with more favorable renal toxicity profiles.

  7. Salicylate-induced changes in immediate-early genes in the hippocampal CA1 area

    Science.gov (United States)

    WU, HAO; XU, FENG-LEI; YIN, YONG; DA, PENG; YOU, XIAO-DONG; XU, HUI-MIN; TANG, YAN

    2015-01-01

    Studies have suggested that salicylate affects neuronal function via interactions with specific membrane channels/receptors. However, the effect of salicylate on activity and synaptic morphology of the hippocampal Cornu Ammonis (CA) 1 area remains to be elucidated. The activation of immediate-early genes (IEGs) was reported to correlate with neuronal activity, in particular activity-regulated cytoskeleton-associated protein and early growth response gene 1. The aim of the present study was to evaluate the expression of these IEGs, as well that of N-methyl D-aspartate (NMDA) receptor subunit 2B in rats following acute and chronic salicylate treatment. Protein and messenger RNA levels of all three genes were increased in rats following chronic administration of salicylate (300 mg/kg for 10 days), returning to baseline levels 14 days post-cessation of treatment. The transient upregulation of gene expression following treatment was accompanied by ultrastructural alterations in hippocampal CA1 area synapses. An increase in synaptic interface curvature was observed as well as an increased number of presynaptic vesicles; in addition, postsynaptic densities thickened and lengthened. In conclusion, the results of the present study indicated that chronic exposure to salicylate may lead to structural alteration of hippocampal CA1 neurons, and it was suggested that this process occurs through induced expression of IEGs via NMDA receptor activation. PMID:25873216

  8. Early bladder outlet obstruction in fetal lambs induces renal dysplasia and the prune-belly syndrome.

    Science.gov (United States)

    Gonzalez, R; Reinberg, Y; Burke, B; Wells, T; Vernier, R L

    1990-03-01

    A model of posterior urethral valves in fetal lambs was developed in order to evaluate the effect of intrauterine urinary obstruction on the developing kidney. Complete urethral obstruction was induced in five fetal lambs at 43 to 45 days of gestation. Two control fetal lambs underwent sham operations. At full term (140 days), two of the five experimental lambs and both control lambs were available for postmortem examination. Results of gross and histological examination of the control lambs were normal. In contrast, the kidneys of the experimental lambs were markedly asymmetrical in size. Histological examination of the kidneys in experimental lambs showed cystic dilatation of the collecting ducts and occasional cystic dilatation of Bowman's spaces, features compatible with obstruction. Also noted were peripheral cortical cysts and primitive tubules lined with cuboidal epithelium and surrounded by fibromuscular collarettes, characteristic of renal dysplasia. One of the infant lambs had many characteristics of the prune-belly syndrome, including a wrinkled, markedly distended abdomen, deficient abdominal wall musculature, flared chest wall, limb deformities, and undescended testes. These results suggest that early in utero urethral obstruction (at the beginning of the second third of gestation) causes renal dysplasia. The results also support the hypothesis that the prune-belly syndrome results from abdominal distention that occurs early in gestation.

  9. Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Bucolo, Claudio; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore

    2012-07-01

    Diabetic retinopathy is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. We hypothesized that eriodictyol, one of the most abundant dietary flavonoids, could be effective against diabetic retinopathy, which involves significant oxidative stress and inflammation. The aim of the present study was to investigate the effects of eriodictyol in early retinal and plasma changes of streptozotocin-induced diabetic rats. The effect of eriodictyol treatment (0.1, 1, 10 mg/kg daily for 10 days) was evaluated by TNF-α, ICAM-1, VEGF, and eNOS protein levels measurement in the retina, plasma lipid peroxidation, and blood-retinal barrier (BRB) integrity. Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina from diabetic rats. Eriodictyol treatment significantly lowered retinal TNF-α, ICAM-1, VEGF, and eNOS in a dose-dependent manner. Further, treatment with eriodictyol significantly suppressed diabetes-related lipid peroxidation, as well as the BRB breakdown. These data demonstrated that eriodictyol attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the BRB in early diabetic rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Epigenetic changes in the early stage of silica-induced cell transformation.

    Science.gov (United States)

    Seidel, Carole; Kirsch, Anaïs; Fontana, Caroline; Visvikis, Athanase; Remy, Aurélie; Gaté, Laurent; Darne, Christian; Guichard, Yves

    2017-09-01

    The increasing use of nanomaterials in numerous domains has led to growing concern about their potential toxicological properties, and the potential risk to human health posed by silica nanoparticles remains under debate. Recent studies proposed that these particles could alter gene expression through the modulation of epigenetic marks, and the possible relationship between particle exposure and these mechanisms could represent a critical factor in carcinogenicity. In this study, using the Bhas 42 cell model, we compare the effects of exposure to two transforming particles, a pyrogenic amorphous silica nanoparticle NM-203 to those of the crystalline silica particle Min-U-Sil ® 5. Short-term treatment by Min-U-Sil ® 5 decreased global DNA methylation and increased the expression of the two de novo DNMTs, DNMT3a and DNMT3b. NM-203 treatment affected neither the expression of these enzymes nor DNA methylation. Moreover, modified global histone H4 acetylation status and HDAC protein levels were observed only in the Min-U-Sil ® 5-treated cells. Finally, both types of particle treatment induced strong c-Myc expression in the early stage of cell transformation and this correlated with enrichment in RNA polymerase II as well as histone active marks on its promoter. Lastly, almost all parameters that were modulated in the early stage were restored in transformed cells suggesting their involvement mainly in the first steps of cell transformation.

  11. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira

    2016-01-01

    An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

  12. Egg clutch dehydration induces early hatching in red-eyed treefrogs,Agalychnis callidryas.

    Science.gov (United States)

    Salica, María José; Vonesh, James R; Warkentin, Karen M

    2017-01-01

    Terrestrial eggs have evolved repeatedly in tropical anurans exposing embryos to the new threat of dehydration. Red-eyed treefrogs, Agalychnis callidryas, lay eggs on plants over water. Maternally provided water allows shaded eggs in humid sites to develop to hatching without rainfall, but unshaded eggs and those in less humid sites can die from dehydration. Hatching responses of amphibian eggs to dry conditions are known from two lineages with independent origins of terrestrial eggs. Here, we experimentally tested for dehydration-induced early hatching in another lineage ( Agalychnis callidryas, Phyllomedusidae), representing a third independent origin of terrestrial eggs. We also investigated how dehydration affected egg and clutch structure, and egg mortality. We collected clutches from a pond in Gamboa, Panama, and randomly allocated them to wet or dry treatments at age 1 day. Embryos hatched earlier from dry clutches than from wet clutches, accelerating hatching by ∼11%. Clutch thickness and egg diameter were affected by dehydration, diverging between treatments over time. Meanwhile, mortality in dry clutches was six-fold higher than in control clutches. With this study, early hatching responses to escape mortality from egg dehydration are now known from three anuran lineages with independent origins of terrestrial eggs, suggesting they may be widespread. Further studies are needed to understand how terrestrial amphibian eggs can respond to, or will be affected by, rapid changes in climate over the next decades.

  13. Early transcriptional responses to mercury: a role for ethylene in mercury-induced stress.

    Science.gov (United States)

    Montero-Palmero, M Belén; Martín-Barranco, Amanda; Escobar, Carolina; Hernández, Luis E

    2014-01-01

    Understanding the cellular mechanisms of plant tolerance to mercury (Hg) is important for developing phytoremediation strategies of Hg-contaminated soils. The early responses of alfalfa (Medicago sativa) seedlings to Hg were studied using transcriptomics analysis. A Medicago truncatula microarray was hybridized with high-quality root RNA from M. sativa treated with 3 μM Hg for 3, 6 and 24 h. The transcriptional pattern data were complementary to the measurements of root growth inhibition, lipid peroxidation, hydrogen peroxide (H2 O2 ) accumulation and NADPH-oxidase activity as stress indexes. Of 559 differentially expressed genes (DEGs), 91% were up-regulated. The majority of DEGs were shared between the 3 and 6 h (60%) time points, including the 'stress', 'secondary metabolism' and 'hormone metabolism' functional categories. Genes from ethylene metabolism and signalling were highly represented, suggesting that this phytohormone may be relevant for metal perception and homeostasis. Ethylene-insensitive alfalfa seedlings preincubated with the ethylene signalling inhibitor 1-methylcyclopronene and Arabidopsis thaliana ein2-5 mutants confirmed that ethylene participates in the early perception of Hg stress. It modulates root growth inhibition, NADPH-oxidase activity and Hg-induced apoplastic H2 O2 accumulation. Therefore, ethylene signalling attenuation could be useful in future phytotechnological applications to ameliorate stress symptoms in Hg-polluted plants. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  14. Egg clutch dehydration induces early hatching in red-eyed treefrogs, Agalychnis callidryas

    Directory of Open Access Journals (Sweden)

    María José Salica

    2017-07-01

    Full Text Available Terrestrial eggs have evolved repeatedly in tropical anurans exposing embryos to the new threat of dehydration. Red-eyed treefrogs, Agalychnis callidryas, lay eggs on plants over water. Maternally provided water allows shaded eggs in humid sites to develop to hatching without rainfall, but unshaded eggs and those in less humid sites can die from dehydration. Hatching responses of amphibian eggs to dry conditions are known from two lineages with independent origins of terrestrial eggs. Here, we experimentally tested for dehydration-induced early hatching in another lineage (Agalychnis callidryas, Phyllomedusidae, representing a third independent origin of terrestrial eggs. We also investigated how dehydration affected egg and clutch structure, and egg mortality. We collected clutches from a pond in Gamboa, Panama, and randomly allocated them to wet or dry treatments at age 1 day. Embryos hatched earlier from dry clutches than from wet clutches, accelerating hatching by ∼11%. Clutch thickness and egg diameter were affected by dehydration, diverging between treatments over time. Meanwhile, mortality in dry clutches was six-fold higher than in control clutches. With this study, early hatching responses to escape mortality from egg dehydration are now known from three anuran lineages with independent origins of terrestrial eggs, suggesting they may be widespread. Further studies are needed to understand how terrestrial amphibian eggs can respond to, or will be affected by, rapid changes in climate over the next decades.

  15. Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development.

    Science.gov (United States)

    Alonso, M I; Martín, C; Carnicero, E; Bueno, D; Gato, A

    2011-07-01

    Embryonic-cerebrospinal fluid (E-CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E-CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E-CSF contains all-trans-retinol and retinol-binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic-rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E-CSF helps to control RA synthesis in the IsO by means of the RBP and all-trans-retinol it contains; (2) E-CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E-CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. Copyright © 2011 Wiley-Liss, Inc.

  16. Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

    Science.gov (United States)

    Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

    2014-01-01

    A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

  17. A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Tamer A Sharafeldin

    Full Text Available Newly emergent turkey arthritis reoviruses (TARV were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O'Neil strain. Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi. Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1-2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV.

  18. A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses.

    Science.gov (United States)

    Sharafeldin, Tamer A; Mor, Sunil K; Sobhy, Nader M; Xing, Zheng; Reed, Kent M; Goyal, Sagar M; Porter, Robert E

    2015-01-01

    Newly emergent turkey arthritis reoviruses (TARV) were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O'Neil strain). Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi). Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1-2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ) at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV.

  19. School Desegregation and Federal Inducement: Lessons from the Emergency School Aid Act of 1972

    Science.gov (United States)

    Hodge, Emily M.

    2018-01-01

    This study uses the example of the Emergency School Aid Act of 1972, a federal desegregation incentive program, to discuss the benefits and challenges of equity-oriented incentives. This study applies theories of policy instruments and the social construction of target populations to congressional records, archival program materials, and other…

  20. Neutrino-Induced Nucleosynthesis in Helium Shells of Early Core-Collapse Supernovae

    Directory of Open Access Journals (Sweden)

    Banerjee Projjwal

    2016-01-01

    Full Text Available We summarize our studies on neutrino-driven nucleosynthesis in He shells of early core-collapse supernovae with metallicities of Z ≲ 10−3 Z⊙. We find that for progenitors of ∼ 11–15 M⊙, the neutrons released by 4He(ν¯ee, e+n3H in He shells can be captured to produce nuclei with mass numbers up to A ∼ 200. This mechanism is sensitive to neutrino emission spectra and flavor oscillations. In addition, we find two new primary mechanisms for neutrino-induced production of 9Be in He shells. The first mechanism produces 9Be via 7Li(n,γ8Li(n,γ9Li(e− ν¯ee9Be and relies on a low explosion energy for its survival. The second mechanism operates in progenitors of ∼ 8 M⊙, where 9Be can be produced directly via 7Li(3H, n09Be during the rapid expansion of the shocked Heshell material. The light nuclei 7Li and 3H involved in these mechanisms are produced by neutrino interactions with 4He. We discuss the implications of neutrino-induced nucleosynthesis in He shells for interpreting the elemental abundances in metal-poor stars.

  1. Development of a Murine Model of Early Sepsis in Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Momina Khan

    2014-01-01

    Full Text Available Sepsis, a global health issue, is the most common cause of mortality in the intensive care unit. The aim of this study was to develop a new model of sepsis that investigates the impact of prolonged western diet (WD induced obesity on the response to early sepsis. Male C57BL/6 mice were fed either a high fat WD or normal chow diet (NCD for 6, 15, or 27 weeks. Septic obese mice at 15 and 27 weeks had significantly lower levels of lung myeloperoxidase (26.3 ± 3.80 U/mg tissue compared to age matched ad lib (44.1 ± 2.86 U/mg tissue and diet restricted (63.2 ± 5.60 U/mg tissue controls. Low levels of lung inflammation were not associated with changes in hepatic cytokines and oxidative stress levels. Obese mice had significantly (P<0.0001 larger livers compared to controls. Histological examination of the livers demonstrated that WD fed mice had increased inflammation with pronounced fat infiltration, steatosis, and hepatocyte ballooning. Using this model of prolonged exposure to high fat diet we have data that agree with recent clinical observations suggesting obese individuals are protected from sepsis-induced lung injury. This model will allow us to investigate the links between damage to the hepatic microcirculation, immune response, and lung injury.

  2. Effects of leonurine hydrochloride on medically induced incomplete abortion in early pregnancy rats.

    Science.gov (United States)

    Li, Xia; Yuan, Feng-Lai; Zhao, Yi-Qing; Chen, Fei-Hu; Lu, Wei-Guo; Li, Cheng-Wan; Li, Jian-Ping

    2011-12-01

    To determine the effect of leonurine hydrochloride (LH) on abnormal bleeding induced by medical abortion. Rats had incomplete abortions induced in early pregnancy using mifepristone in combination with misoprostol. After abortion, rats were treated with LH for 7 days, and the duration and volume of uterine bleeding were observed. Approximately 30min after the last treatment, the animals were killed and the uterine shape was observed. The sinistro-uteri were suspended in organ baths to record the contraction curves, including the frequency and tension for 10min; the dextro-uteri were fixed with formaldehyde for pathologic evaluation. In addition, blood samples were collected from the femoral artery for the measurement of estradiol (E₂) and progesterone (P) levels by radioimmunoassay. In in vivo experiments, compared with the model group, LH treatment markedly reduced the volume of bleeding and intrauterine residual, and significantly shortened the duration of bleeding. From the contraction curve, LH notably reinforced the frequency and tension of uterine contractions. LH remarkably elevated the serum estradiol level in rats, but had no obvious effect on progesterone level. LH has an inhibitory effect on bleeding caused by incomplete abortion; the mechanism may be related to up-regulation of the E₂ level, leading to an increase in uterine contractions and evacuation of intrauterine residuum. Copyright © 2011. Published by Elsevier Ireland Ltd.

  3. Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish.

    Science.gov (United States)

    Félix, Luís M; Serafim, Cindy; Valentim, Ana M; Antunes, Luís M; Matos, Manuela; Coimbra, Ana M

    2017-09-05

    Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages). Exposure at the 256-cell stage to ketamine induced an up-regulation of casp8 and pcna at 8 hpf while changes in pcna at the mRNA level were observed at 24 hpf. After the 50% epiboly stage exposure, the mRNA levels of casp9 were increased at 8 and 24 hpf while aifm1 was affected at 24 hpf. Both tp53 and pcna expressions were increased at 8 hpf. After exposure during the 1-4 somites stage, no meaningful changes on transcript levels were observed. The distribution of apoptotic cells and the caspase-like enzymatic activities of caspase-3 and -9 were not affected by ketamine exposure. It is proposed that ketamine exposure at the 256-cell stage induced a cooperative mechanism between proliferation and cellular death while following exposure at the 50% epiboly, a p53-dependent and -independent caspase activation may occur. Finally, at the 1-4 somites stage, the defence mechanisms are already fully in place to protect against ketamine-insult. Thus, ketamine teratogenicity seems to be dependent on the functional mechanisms present in each developmental stage. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?

    Science.gov (United States)

    Holman, Natalie S; Mosedale, Merrie; Wolf, Kristina K; LeCluyse, Edward L; Watkins, Paul B

    2016-06-01

    Drug-induced liver injury (DILI) is a significant clinical and economic problem in the United States, yet the mechanisms that underlie DILI remain poorly understood. Recent evidence suggests that signaling molecules released by stressed hepatocytes can trigger immune responses that may be common across DILI mechanisms. Extracellular vesicles released by hepatocytes, principally hepatocyte-derived exosomes (HDEs), may constitute one such signal. To examine HDE alterations as a function of drug-induced stress, this work utilized prototypical hepatotoxicant acetaminophen (APAP) in male Sprague-Dawley (SD) rats, SD rat hepatocytes, and primary human hepatocytes. HDE were isolated using ExoQuick precipitation reagent and analyzed by quantification of the liver-specific RNAs albumin and microRNA-122 (miR-122). In vivo, significant elevations in circulating exosomal albumin mRNA were observed at subtoxic APAP exposures. Significant increases in exosomal albumin mRNA were also observed in primary rat hepatocytes at subtoxic APAP concentrations. In primary human hepatocytes, APAP elicited increases in both exosomal albumin mRNA and exosomal miR-122 without overt cytotoxicity. However, the number of HDE produced in vitro in response to APAP did not increase with exosomal RNA quantity. We conclude that significant drug-induced alterations in the liver-specific RNA content of HDE occur at subtoxic APAP exposures in vivo and in vitro, and that these changes appear to reflect selective packaging rather than changes in exosome number. The current findings demonstrate that translationally relevant HDE alterations occur in the absence of overt hepatocellular toxicity, and support the hypothesis that HDE released by stressed hepatocytes may mediate early immune responses in DILI. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Early biomarkers of doxorubicin-induced heart injury in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Kwekel, Joshua C.; Vijay, Vikrant; Moland, Carrie L. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Herman, Eugene H. [Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850-9734 (United States); Lee, Taewon [Department of Mathematics, Korea University, Sejong, Chungnam 339-700 (Korea, Republic of); Han, Tao [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Davis, Kelly J.; Muskhelishvili, Levan [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Kerr, Susan [Arkansas Heart Hospital, Little Rock, AR 72211 (United States); Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2014-12-01

    Cardiac troponins, which are used as myocardial injury markers, are released in plasma only after tissue damage has occurred. Therefore, there is a need for identification of biomarkers of earlier events in cardiac injury to limit the extent of damage. To accomplish this, expression profiling of 1179 unique microRNAs (miRNAs) was performed in a chronic cardiotoxicity mouse model developed in our laboratory. Male B6C3F{sub 1} mice were injected intravenously with 3 mg/kg doxorubicin (DOX; an anti-cancer drug), or saline once a week for 2, 3, 4, 6, and 8 weeks, resulting in cumulative DOX doses of 6, 9, 12, 18, and 24 mg/kg, respectively. Mice were euthanized a week after the last dose. Cardiac injury was evidenced in mice exposed to 18 mg/kg and higher cumulative DOX dose whereas examination of hearts by light microscopy revealed cardiac lesions at 24 mg/kg DOX. Also, 24 miRNAs were differentially expressed in mouse hearts, with the expression of 1, 1, 2, 8, and 21 miRNAs altered at 6, 9, 12, 18, and 24 mg/kg DOX, respectively. A pro-apoptotic miR-34a was the only miRNA that was up-regulated at all cumulative DOX doses and showed a significant dose-related response. Up-regulation of miR-34a at 6 mg/kg DOX may suggest apoptosis as an early molecular change in the hearts of DOX-treated mice. At 12 mg/kg DOX, up-regulation of miR-34a was associated with down-regulation of hypertrophy-related miR-150; changes observed before cardiac injury. These findings may lead to the development of biomarkers of earlier events in DOX-induced cardiotoxicity that occur before the release of cardiac troponins. - Highlights: • Upregulation of miR-34a before doxorubicin-induced cardiac tissue injury • Apoptosis might be an early event in mouse heart during doxorubicin treatment. • Expression of miR-150 declined before doxorubicin-induced cardiac tissue injury.

  6. Convention on early notification of a nuclear accident. Convention on assistance in the case of a nuclear accident or radiological emergency

    International Nuclear Information System (INIS)

    1987-05-01

    The document refers to the Convention on early notification of a nuclear accident (INFCIRC-335) and to the Convention on assistance in the case of a nuclear accident or radiological emergency (INFCIRC-336). Part I of the document contains the texts of reservations/declarations made by some of the countries upon or following signature. Part II contains the texts of reservations/declarations made upon or following deposit of instrument, expressing consent to be bound

  7. Convention on early notification of a nuclear accident and convention on assistance in the case of a nuclear accident or radiological emergency

    International Nuclear Information System (INIS)

    1997-01-01

    The document refers to the Convention on Early Notification of a Nuclear Accident (CENNA) (IAEA-INFCIRC-335) and the Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency (CANARE) (IAEA-INFCIRC-336). Part I contains the status list as of 31 December 1996, Part II contains the texts of reservations/declarations made upon or following expressing consent to be bound and objections thereto, and Part III contains the texts of reservations/declarations made upon signature

  8. Convention on early notification of a nuclear accident and convention on assistance in the case of a nuclear accident or radiological emergency

    International Nuclear Information System (INIS)

    1991-09-01

    The document refers to the Convention on Early Notification of a Nuclear Accident (IAEA-INFCIRC-335) and to the Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency (IAEA-INFCIRC-336). Part I contains the status lists as of August 31, 1991. Part II contains reservations/declarations made upon expressing consent to be bound and objections there to. Part III contains reservations/declarations made upon signature

  9. Convention on early notification of a nuclear accident and convention on assistance in the case of a nuclear accident or radiological emergency

    International Nuclear Information System (INIS)

    1992-09-01

    The document refers to the Convention on Early Notification of a Nuclear Accident (CENNA) (IAEA-INFCIRC-335) and the Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency (CANARE) (IAEA-INFCIRC-336). Part I contains the status lists as of 10 September 1992, part II contains the texts of reservations/declarations made upon expressing consent to be bound and objections there to, and part III contains the texts of reservations/declarations made upon signature

  10. Convention on Early Notification of a Nuclear Accident and Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency

    International Nuclear Information System (INIS)

    1997-01-01

    Part I: Status lists as of 31 December 1996. A. Convention on Early Notification of a Nuclear Accident (Notification Convention). B. Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency (Assistance Convention). PART II: Texts of reservations/declarations made upon or following expressing consent to be bound and objections thereto Part III: Texts of reservations/declarations made upon signature

  11. Relationship between Emergent Literacy and Early Social-Emotional Development in Preschool Children from Low-Income Backgrounds

    Science.gov (United States)

    Tan, Minghua; Dobbs-Oates, Jennifer

    2013-01-01

    Sixty-one preschool children and their parents and teachers participated in a cross-sectional study of the social-emotional correlates of emergent literacy skills. The children's emergent literacy skills were assessed with the standard language and literacy tests: "Expressive Vocabulary Test, Peabody Picture Vocabulary Test" (third…

  12. Early life DNA vaccination with the H gene of Canine distemper virus induces robust protection against distemper

    DEFF Research Database (Denmark)

    Jensen, Trine Hammer; Nielsen, Line; Aasted, Bent

    2009-01-01

    Young mink kits (n = 8)were vaccinated withDNA plasmids encoding the viral haemagglutinin protein (H) of a vaccine strain of Canine distemper virus (CDV). Virus neutralising (VN) antibodieswere induced after 2 immunisations and after the third immunisation all kits had high VN antibody titres...... demonstrate that early life DNA vaccination with the H gene of a CDV vaccine strain induced robust protective immunity against a recent wild type CDV....

  13. Early inflammatory changes in radiation-induced oral mucositis. Effect of pentoxifylline in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, Sylvia; Bozsaky, Eva; Roitinger, Eva; Schwarz, Karoline [Medical University/AKH Vienna, Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Vienna (Austria); Schmidt, Margret [Technische Universitaet Dresden, Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Technische Universitaet Dresden, Helmholtz-Zentrum Dresden - Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Doerr, Wolfgang [Medical University/AKH Vienna, Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Vienna (Austria); Technische Universitaet Dresden, Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany); Technische Universitaet Dresden, Helmholtz-Zentrum Dresden - Rossendorf, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden (Germany)

    2017-06-15

    Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline. Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed. Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB. Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation. (orig.) [German] Fruehe entzuendliche Veraenderungen sind ein bedeutender Faktor waehrend der Strahlenreaktion der Schleimhaut. Die Behandlung mit Pentoxifyllin erzielte eine signifikante Minderung strahleninduzierter oraler Mukositis im Mauszungenmodel. Die zugrundeliegenden Mechanismen sind potenziell auf die immunomodulatorischen Eigenschaften des Wirkstoffs zurueckzufuehren. Die vorliegenden Untersuchungen fokussieren daher auf die Manifestation frueher entzuendlicher Veraenderungen in der Mauszunge waehrend taeglich fraktionierter Bestrahlung und deren potenzieller Modifikation

  14. C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.

    Science.gov (United States)

    Nath, Ravi D; Chow, Elly S; Wang, Han; Schwarz, Erich M; Sternberg, Paul W

    2016-09-26

    The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through epidermal growth factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA sequencing of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in nlp-8; flp-24; flp-13 triple-mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep-pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus-and we found that, if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual neuropeptides or combinations of neuropeptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The effectiveness of physiologically based early warning or track and trigger systems after triage in adult patients presenting to emergency departments: a systematic review.

    Science.gov (United States)

    Wuytack, Francesca; Meskell, Pauline; Conway, Aislinn; McDaid, Fiona; Santesso, Nancy; Hickey, Fergal G; Gillespie, Paddy; Raymakers, Adam J N; Smith, Valerie; Devane, Declan

    2017-12-06

    Changes to physiological parameters precede deterioration of ill patients. Early warning and track and trigger systems (TTS) use routine physiological measurements with pre-specified thresholds to identify deteriorating patients and trigger appropriate and timely escalation of care. Patients presenting to the emergency department (ED) are undiagnosed, undifferentiated and of varying acuity, yet the effectiveness and cost-effectiveness of using early warning systems and TTS in this setting is unclear. We aimed to systematically review the evidence on the use, development/validation, clinical effectiveness and cost-effectiveness of physiologically based early warning systems and TTS for the detection of deterioration in adult patients presenting to EDs. We searched for any study design in scientific databases and grey literature resources up to March 2016. Two reviewers independently screened results and conducted quality assessment. One reviewer extracted data with independent verification of 50% by a second reviewer. Only information available in English was included. Due to the heterogeneity of reporting across studies, results were synthesised narratively and in evidence tables. We identified 6397 citations of which 47 studies and 1 clinical trial registration were included. Although early warning systems are increasingly used in EDs, compliance varies. One non-randomised controlled trial found that using an early warning system in the ED may lead to a change in patient management but may not reduce adverse events; however, this is uncertain, considering the very low quality of evidence. Twenty-eight different early warning systems were developed/validated in 36 studies. There is relatively good evidence on the predictive ability of certain early warning systems on mortality and ICU/hospital admission. No health economic data were identified. Early warning systems seem to predict adverse outcomes in adult patients of varying acuity presenting to the ED but there

  16. The Role of Early Maturation, Perceived Popularity, and Rumors in the Emergence of Internalizing Symptoms among Adolescent Girls

    Science.gov (United States)

    Reynolds, Bridget M.; Juvonen, Jaana

    2011-01-01

    Despite the widely reported link between early pubertal timing and internalizing symptoms among girls, less is known about the peer reputation of earlier maturing girls. The current study assesses whether early maturation is associated with perceived popularity and/or rumors, and whether these reputational factors help account for earlier maturing…

  17. The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia

    NARCIS (Netherlands)

    Duarte, C; Mauricio, J; Pettitt, PB; Souto, P; Trinkaus, E; van der Plicht, H; Zilhao, J; Pettitt, Paul B.

    1999-01-01

    The discovery of an early Upper Paleolithic human burial at the Abrigo do Lagar Velho, Portugal, has provided evidence of early modern humans from southern Iberia, The remains, the largely complete skeleton of a;approximate to 4-year-old child buried with pierced shell and red ochre, is dated to ca,

  18. Salicylate Functions as an Efflux Pump Inducer and Promotes the Emergence of Fluoroquinolone-Resistant Campylobacter jejuni Mutants▿

    Science.gov (United States)

    Shen, Zhangqi; Pu, Xiao-Ying; Zhang, Qijing

    2011-01-01

    Salicylate, a nonsteroidal anti-inflammatory compound, has been shown to increase the resistance of Campylobacter to antimicrobials. However, the molecular mechanism underlying salicylate-induced resistance has not yet been established. In this study, we determined how salicylate increases antibiotic resistance and evaluated its impact on the development of fluoroquinolone-resistant Campylobacter mutants. Transcriptional fusion assays, real-time quantitative reverse transcription-PCR (RT-PCR), and immunoblotting assays consistently demonstrated the induction of the CmeABC multidrug efflux pump by salicylate. Electrophoretic mobility shift assays further showed that salicylate inhibits the binding of CmeR (a transcriptional repressor of the TetR family) to the promoter DNA of cmeABC, suggesting that salicylate inhibits the function of CmeR. The presence of salicylate in the culture medium not only decreased the susceptibility of Campylobacter to ciprofloxacin but also resulted in an approximately 70-fold increase in the observed frequency of emergence of fluoroquinolone-resistant mutants under selection with ciprofloxacin. Together, these results indicate that in Campylobacter, salicylate inhibits the binding of CmeR to the promoter DNA and induces expression of cmeABC, resulting in decreased susceptibility to antibiotics and in increased emergence of fluoroquinolone-resistant mutants under selection pressure. PMID:21821741

  19. Endogenous hydrogen sulfide mediates the cardioprotection induced by ischemic postconditioning in the early reperfusion phase.

    Science.gov (United States)

    Huang, Yi-E; Tang, Zhi-Han; Xie, Wei; Shen, Xin-Tian; Liu, Mi-Hua; Peng, Xiang-Ping; Zhao, Zhan-Zhi; Nie, DE-Bo; Liu, Lu-Shan; Jiang, Zhi-Sheng

    2012-12-01

    Hydrogen sulfide (H(2)S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, has been suggested to be the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). The present study aimed to investigate the role of H(2)S in ischemic postconditioning (IPO) during the early period of reperfusion. IPO with 6 episodes of 10 sec reperfusion followed by 6 episodes of 10 sec ischemia (IPO 2') was administered when reperfusion was initiated. Cardiodynamics and the concentration of H(2)S were measured at 1, 2, 3, 4, 5, 10, 20, 30, 60, 90 and 120 min of reperfusion. Lactate dehydrogenase (LDH) levels and infarct size were determined at the end of the reperfusion. The concentration of H(2)S was stable during the whole experiment in the control group, whereas it reached a peak at the first minute of reperfusion in the ischemia-reperfusion (IR) group. The concentration of H(2)S at the first minute of reperfusion in the IPO 2' group was higher compared to that of the IR group, which correlated with cardioprotection including improved heart contractile function and reduced infarct size and LDH levels. However, the above effects of IPO 2' were attenuated by pre-treatment with blockade of endogenous H(2)S production with DL-propargylglycine for 20 min prior to global ischemia. Furthermore, we found that other forms of IPO, IPO commencing at 1 min after reperfusion (delayed IPO) or lasting only for 1 min (IPO 1'), failed to increase the concentration of H(2)S and protect the myocardium. We conclude that the peak of endogenous H(2)S in the early reperfusion phase is the key to cardioprotection induced by IPO.

  20. The effect of short-term vitamin E against radioiodine-induced early lacrimal gland damage

    International Nuclear Information System (INIS)

    Acar, Ugur; Atilgan, Hasan Ikbal; Acar, Damla Erginturk; Yalniz-Akkaya, Zuleyha; Korkmaz, Meliha; Koca, Goekhan; Yumusak, Nihat

    2013-01-01

    Radioiodine (RAI) is a well-known radionuclide which is used in vivo both for diagnostic and therapeutic purposes, particularly for the treatment of hyperthyroidism and thyroid cancer. Vitamin E is a well-known antioxidant vitamin. The aim of this study was to evaluate whether there was a protective effect of short-term vitamin E on RAI-induced lacrimal gland early damage in experimental animal models. Twentyfour rats were randomly divided into two groups. The first group (RAI group) was administreted 3 mCi 131 I by gastric gavage and 1 mL physiological saline intraperitoneally. The second group (RAI+Vitamin E) was administrated 3 mCi 131 I by gastric gavage and 1 mL vitamin E intraperitoneally. After 24 h of the last dose being administered on the 7th day, the animals were decapitated. The lacrimal glands [Intraorbital (IG), extraorbital (EG) and harderian glands (HG)] of the rats were removed for histopathological examination. Periductal and/or periacinar fibrosis in all lacrimal glands were observed to be statistically significantly less frequent in the RAI + Vitamin E group compared to the RAI group. The existence of the abnormal lobular pattern and peripheral basophilia and irregular nucleus shape in IG and in EG, the poorly defined acidophilic cell outline and periductal infiltration in IG and in HG were observed to be statistically significantly less frequent in the RAI + Vitamin E group than in the RAI group. According to study results, histopathological examinations revealed that vitamin E protects rat lacrimal glands against RAI-related early damage. (author)

  1. An improved method of early diagnosis of smoking-induced respiratory changes using machine learning algorithms.

    Science.gov (United States)

    Amaral, Jorge L M; Lopes, Agnaldo J; Jansen, José M; Faria, Alvaro C D; Melo, Pedro L

    2013-12-01

    The purpose of this study was to develop an automatic classifier to increase the accuracy of the forced oscillation technique (FOT) for diagnosing early respiratory abnormalities in smoking patients. The data consisted of FOT parameters obtained from 56 volunteers, 28 healthy and 28 smokers with low tobacco consumption. Many supervised learning techniques were investigated, including logistic linear classifiers, k nearest neighbor (KNN), neural networks and support vector machines (SVM). To evaluate performance, the ROC curve of the most accurate parameter was established as baseline. To determine the best input features and classifier parameters, we used genetic algorithms and a 10-fold cross-validation using the average area under the ROC curve (AUC). In the first experiment, the original FOT parameters were used as input. We observed a significant improvement in accuracy (KNN=0.89 and SVM=0.87) compared with the baseline (0.77). The second experiment performed a feature selection on the original FOT parameters. This selection did not cause any significant improvement in accuracy, but it was useful in identifying more adequate FOT parameters. In the third experiment, we performed a feature selection on the cross products of the FOT parameters. This selection resulted in a further increase in AUC (KNN=SVM=0.91), which allows for high diagnostic accuracy. In conclusion, machine learning classifiers can help identify early smoking-induced respiratory alterations. The use of FOT cross products and the search for the best features and classifier parameters can markedly improve the performance of machine learning classifiers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis

    International Nuclear Information System (INIS)

    Muto, Masahiro; Ying Chen; Kubo, Eiko; Mita, Kazuei

    1996-01-01

    Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of γ T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2 + (TL-2 + ) thymocytes. Limited numbers of TL-2 + cells from individual irradiated B10.Thy-1.1 mice were injected into B10.Thy-1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F; 10C), t(1A; 13D) or t(6A; XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after γ T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after γ TCR rearrangements. (author)

  3. Effects of constraint-induced movement therapy on neurogenesis and functional recovery after early hypoxic-ischemic injury in mice.

    Science.gov (United States)

    Rha, Dong-Wook; Kang, Seong-Woong; Park, Yoon-Ghil; Cho, Sung-Rae; Lee, Won Taek; Lee, Jong Eun; Nam, Chung Mo; Han, Kyung Hwa; Park, Eun Sook

    2011-04-01

    Constraint-induced movement therapy (CIMT) has emerged as a promising therapeutic strategy for improving affected upper limb function in children with hemiplegic cerebral palsy (CP). However, little is known about the changes in the brain that are induced by CIMT. This study was designed to investigate these changes and behavioural performance after CIMT intervention in mice with neonatal hypoxic-ischemic brain injury. We utilized the neonatal hypoxic-ischemic brain injury model established in mice pups. Three weeks after the injury, the mice were randomly assigned to the following three groups: the control group (n = 15), the enriched-environment group (n = 17), and the CIMT with an enriched-environment group (CIMT-EE, n = 15). 5-bromo-2-deoxyuridine (BrdU) was injected daily to label proliferating cells during the 2 weeks of intervention. The CIMT-EE group showed better fall rate in the horizontal ladder rung walking test (mean 5.4%, SD 3.6%) than either the control (mean 14.3%, SD 7.3%; p = 0.001) or enriched-environment (mean 12.4%, SD 7.7%; p = 0.010) groups 2 weeks after the end of intervention. The CIMT-EE group also showed more neurogenesis (mean 7069 cells/mm³, SD 4017 cells/mm³) than either the control group (mean 1555 cells/mm³, SD 1422 cells/mm³; p < 0.001) or enriched-environment group (mean 2994 cells/mm³, SD 3498 cells/mm³; p = 0.001) in the subventricular zone. In the striatum, neurogenesis in the CIMT-EE group (mean 534 cells/mm³, SD 441 cells/mm³) was greater than in the control group (mean 95 cells/mm³, SD 133 cells/mm³; p = 0.001). There was CIMT-EE enhanced neurogenesis in the brain along with functional benefits in mice after early hypoxic-ischemic brain injury. This is the first study to demonstrate the effects of CIMT on neurogenesis and functional recovery after experimental injury to an immature brain. © The Authors. Journal compilation © Mac Keith Press 2011.

  4. Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis.

    Science.gov (United States)

    Vidal, Bruno; Cascão, Rita; Finnilä, Mikko A J; Lopes, Inês P; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João E

    2018-01-01

    Arthritis induces joint erosions and skeletal bone fragility. The main goal of this work was to analyze the early arthritis induced events at bone architecture and mechanical properties at tissue level. Eighty-eight Wistar rats were randomly housed in experimental groups, as follows: adjuvant induced arthritis (AIA) (N = 47) and a control healthy group (N = 41). Rats were monitored during 22 days for the inflammatory score, ankle perimeter and body weight and sacrificed at different time points (11 and 22 days post disease induction). Bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. At bone tissue level, measured by nanoindentation, there was a reduction of hardness in the arthritic group, associated with an increase of the ratio of bone concentric to parallel lamellae and of the area of the osteocyte lacuna. In addition, increased bone turnover and changes in the microstructure and mechanical properties were observed in arthritic animals, since the early phase of arthritis, when compared with healthy controls. We have shown in an AIA rat model that arthritis induces very early changes at bone turnover, structural degradation and mechanical weakness. Bone tissue level is also affected since the early phase of arthritis, characterized by decreased tissue hardness associated with changes in bone lamella organization and osteocyte lacuna surface. These observations highlight the pertinence of immediate control of inflammation in the initial stages of arthritis.

  5. Direct Observation of Early-Stage High-Dose Radiotherapy-Induced Vascular Injury via Basement Membrane-Targeting Nanoparticles.

    Science.gov (United States)

    Au, Kin Man; Hyder, Sayed Nabeel; Wagner, Kyle; Shi, Caihong; Kim, Young Seok; Caster, Joseph M; Tian, Xi; Min, Yuanzeng; Wang, Andrew Z

    2015-12-22

    Collagen IV-targeting peptide-conjugated basement membrane-targeting nanoparticles are successfully engineered to identify early-stage blood vessel injury induced by high-dose radiotherapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Metal-induced malformations in early Palaeozoic plankton are harbingers of mass extinction.

    Science.gov (United States)

    Vandenbroucke, Thijs R A; Emsbo, Poul; Munnecke, Axel; Nuns, Nicolas; Duponchel, Ludovic; Lepot, Kevin; Quijada, Melesio; Paris, Florentin; Servais, Thomas; Kiessling, Wolfgang

    2015-08-25

    Glacial episodes have been linked to Ordovician-Silurian extinction events, but cooling itself may not be solely responsible for these extinctions. Teratological (malformed) assemblages of fossil plankton that correlate precisely with the extinction events can help identify alternate drivers of extinction. Here we show that metal poisoning may have caused these aberrant morphologies during a late Silurian (Pridoli) event. Malformations coincide with a dramatic increase of metals (Fe, Mo, Pb, Mn and As) in the fossils and their host rocks. Metallic toxins are known to cause a teratological response in modern organisms, which is now routinely used as a proxy to assess oceanic metal contamination. Similarly, our study identifies metal-induced teratology as a deep-time, palaeobiological monitor of palaeo-ocean chemistry. The redox-sensitive character of enriched metals supports emerging 'oceanic anoxic event' models. Our data suggest that spreading anoxia and redox cycling of harmful metals was a contributing kill mechanism during these devastating Ordovician-Silurian palaeobiological events.

  7. [Postpartum hemorrhage and pregnancy induced hypertension during emergency lower segment cesarean section: dexmedetomidine to our rescue].

    Science.gov (United States)

    Hariharan, Uma

    Dexmedetomidine is a highly selective α-2 agonist which has recently revolutionized our anesthesia and intensive care practice. An obstetric patient presented for emergency cesarean delivery under general anesthesia, with pre-eclampsia and postpartum hemorrhage. In carefully selected cases with refractory hypertension and postpartum hemorrhage, dexmedetomidine can be used for improving overall patient outcome. It was beneficial in controlling both the blood pressure and uterine bleeding during cesarean section in our patient. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  8. Successful emergency splenectomy during cardiac arrest due to cytomegalovirus-induced atraumatic splenic rupture

    DEFF Research Database (Denmark)

    Glesner, Matilde Kanstrup; Madsen, Kristian Rørbæk; Nielsen, Jesper Meng Rahn

    2015-01-01

    A 27-year-old woman was admitted to the emergency department with fever and a petechial rash on suspicion of meningitis. Shortly after arriving she developed cardiac arrest. Blood work up showed severe lactate acidosis, anaemia and thrombocytopenia. A focused assessment with sonography in trauma...... for 14 days with ganciclovir and meropenem and discharged on recovery. Atraumatic splenic rupture caused by viral infection is a rare condition although well described. In the case of our patient, thrombocytopenia added to the severity of the splenic rupture. A multidisciplinary team approach...

  9. Early life stress induces immune priming in kidneys of adult male rats.

    Science.gov (United States)

    De Miguel, Carmen; Obi, Ijeoma E; Ho, Dao H; Loria, Analia S; Pollock, Jennifer S

    2018-03-01

    Early life stress (ELS) in humans is associated with elevated proinflammatory markers. We hypothesized that ELS induces activation of the immune response in a rat model of ELS, maternal separation (MatSep), in adulthood. MatSep involves separating pups from the dam from postnatal day 2 to postnatal day 14 for 3 h/day. Control rats are nonseparated littermates. We determined circulating and renal immune cell numbers, renal immune cell activation markers, renal cytokine levels, and the renal inflammatory gene expression response to low-dose lipopolysaccharide (LPS) in male MatSep and control rats. We observed that MatSep did not change the percentage of gated events for circulating CD3 + , CD4 + , CD8 + , and CD4 + /Foxp3 + cells or absolute numbers of mononuclear and T cells in the circulation and kidneys; however, MatSep led to an increase in activation of renal neutrophils as well as CD44 + cells. Renal toll-like receptor 4 (TLR4) and interleukin 1 beta (IL-1β) was significantly increased in MatSep rats, specifically in the outer and inner medulla and distal nephron, respectively. Evaluation of renal inflammatory genes showed that in response to a low-dose LPS challenge (2 mg/kg iv) a total of 20 genes were significantly altered in kidneys from MatSep rats (17 genes were upregulated and 3 were downregulated), as opposed to no significant differences in gene expression in control vs. control + LPS groups. Taken together, these findings indicate that MatSep induces priming of the immune response in the kidney.

  10. Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction

    Directory of Open Access Journals (Sweden)

    Leppert W

    2015-04-01

    Full Text Available Wojciech Leppert Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland Abstract: Opioid-induced bowel dysfunction (OIBD comprises gastrointestinal (GI symptoms, including dry mouth, nausea, vomiting, gastric stasis, bloating, abdominal pain, and opioid-induced constipation, which significantly impair patients’ quality of life and may lead to undertreatment of pain. Traditional laxatives are often prescribed for OIBD symptoms, although they display limited efficacy and exert adverse effects. Other strategies include prokinetics and change of opioids or their administration route. However, these approaches do not address underlying causes of OIBD associated with opioid effects on mostly peripheral opioid receptors located in the GI tract. Targeted management of OIBD comprises purely peripherally acting opioid receptor antagonists and a combination of opioid receptor agonist and antagonist. Methylnaltrexone induces laxation in 50%–60% of patients with advanced diseases and OIBD who do not respond to traditional oral laxatives without inducing opioid withdrawal symptoms with similar response (45%–50% after an oral administration of naloxegol. A combination of prolonged-release oxycodone with prolonged-release naloxone (OXN in one tablet (a ratio of 2:1 provides analgesia with limited negative effect on the bowel function, as oxycodone displays high oral bioavailability and naloxone demonstrates local antagonist effect on opioid receptors in the GI tract and is totally inactivated in the liver. OXN in daily doses of up to 80 mg/40 mg provides equally effective analgesia with improved bowel function compared to oxycodone administered alone in patients with chronic non-malignant and cancer-related pain. OIBD is a common complication of long-term opioid therapy and may lead to quality of life deterioration and undertreatment of pain. Thus, a complex assessment and management that addresses underlying

  11. Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

    Directory of Open Access Journals (Sweden)

    Asquith Kelly L

    2010-02-01

    Full Text Available Abstract Background Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV, increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. Methods We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR and host immunological responses. Results Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice

  12. Challenges for operational forecasting and early warning of rainfall induced landslides

    Science.gov (United States)

    Guzzetti, Fausto

    2017-04-01

    In many areas of the world, landslides occur every year, claiming lives and producing severe economic and environmental damage. Many of the landslides with human or economic consequences are the result of intense or prolonged rainfall. For this reason, in many areas the timely forecast of rainfall-induced landslides is of both scientific interest and social relevance. In the recent years, there has been a mounting interest and an increasing demand for operational landslide forecasting, and for associated landslide early warning systems. Despite the relevance of the problem, and the increasing interest and demand, only a few systems have been designed, and are currently operated. Inspection of the - limited - literature on operational landslide forecasting, and on the associated early warning systems, reveals that common criteria and standards for the design, the implementation, the operation, and the evaluation of the performances of the systems, are lacking. This limits the possibility to compare and to evaluate the systems critically, to identify their inherent strengths and weaknesses, and to improve the performance of the systems. Lack of common criteria and of established standards can also limit the credibility of the systems, and consequently their usefulness and potential practical impact. Landslides are very diversified phenomena, and the information and the modelling tools used to attempt landslide forecasting vary largely, depending on the type and size of the landslides, the extent of the geographical area considered, the timeframe of the forecasts, and the scope of the predictions. Consequently, systems for landslide forecasting and early warning can be designed and implemented at several different geographical scales, from the local (site or slope specific) to the regional, or even national scale. The talk focuses on regional to national scale landslide forecasting systems, and specifically on operational systems based on empirical rainfall threshold

  13. The Effectiveness of Early Educational Interventions in the Emergency Department to Reduce Incidence or Severity of Postconcussion Syndrome Following a Concussion: A Systematic Review.

    Science.gov (United States)

    Eliyahu, Leeor; Kirkland, Scott; Campbell, Sandy; Rowe, Brian H

    2016-05-01

    Concussions or mild traumatic brain injury are a major public health concern accounting for 85% of all brain injuries. Postconcussion syndrome (PCS) has been found to affect between 15 and 25% of patients with concussion 1 year after the initial injury. The goal of this review is to assess the effectiveness of early educational information or interventions provided in the emergency department on the onset and/or severity of PCS. A comprehensive literature search strategy involving seven electronic databases was developed. A grey literature search of Google Scholar, recent conference proceedings in emergency medicine, bibliographies of included studies, and clinical trial registries was also performed. The citation list was reviewed independently by two reviewers; no restrictions on publication status or language of publication were applied. The Cochrane risk-of-bias tool and the Newcastle-Ottawa scale were used to assess quality. From 1,325 citations retrieved, four RCTs and one controlled clinical trial met inclusion criteria. Interventions identified in these studies included: educational information sheets, with or without telephone or in-person follow-up, and one study on bed rest. While rarely requested, one study offered referrals and additional treatment, if needed. None of the studies were deemed to be high quality. Heterogeneity among outcome reporting, follow-up dates and interventions used precluded a pooled analysis. Overall, only two of the five included studies involving adult patients receiving early educational interventions reported a significant improvement in PCS symptoms. No reduction in PCS symptoms was found in the study on bed rest interventions. Limited evidence exists regarding the effectiveness of early educational interventions following concussion. Standardization of the interventions, outcome measures, and follow-up periods would make quantitative comparisons more valid. Moreover, higher-quality research in the field of early

  14. Early cannabis use is associated with severity of Cocaine-Induced Psychosis among cocaine smokers in Martinique, French West Indies.

    Science.gov (United States)

    Trape, Sandrine; Charles-Nicolas, Aimé; Jehel, Louis; Lacoste, Jérôme

    2014-01-01

    Cocaine intoxication can induce transient psychotic symptoms. The principal aim of this study was to determine sociodemographic and clinical characteristics associated with cocaine-induced psychosis (CIP) and to identify clinical factors predicting CIP in crack cocaine smokers in Martinique. The second aim was to identify clinical factors associated with severity of CIP, assessed with the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP). Fifty-three cocaine-dependent smokers (45 men and 8 women) seeking treatment for cocaine dependence were included. Patients were assessed using the Cocaine Experience Questionnaire (CEQ), an instrument for the identification of cocaine-induced paranoia, and a French version of the SAPS-CIP, for the severity of CIP. Thirty-five (66%) patients reported cocaine-induced paranoia on the CEQ (CIP(+) patients). The mean SAPS-CIP total score was 6.1 ± 3.7, with a significant difference between CIP(+) and CIP(-) patients (P crack cocaine smokers in Martinique, and early cannabis use is associated with the occurrence and the severity of psychotic symptoms during cocaine intoxication in this population. Patients developing psychotic symptoms during cocaine use began smoking cannabis earlier during adolescence than patients without CIP. These results confirm those of previous studies, highlighting the need to better assess early cannabis use in cocaine users, because early cannabis use is associated with severity of CIP.

  15. Emergent bimodality and switch induced by time delays and noises in a synthetic gene circuit

    Science.gov (United States)

    Zhang, Chun; Du, Liping; Xie, Qingshuang; Wang, Tonghuan; Zeng, Chunhua; Nie, Linru; Duan, Weilong; Jia, Zhenglin; Wang, Canjun

    2017-10-01

    Based on the kinetic model for obtaining emergent bistability proposed by Tan et al. (2009), the effects of the fluctuations of protein synthesis rate and maximum dilution rate, the cross-correlation between two noises, and the time delay and the strength of the feedback loop in the synthetic gene circuit have been investigated through theoretical analysis and numerical simulation. Our results show that: (i) the fluctuations of protein synthesis rate and maximum dilution rate enhance the emergent bimodality of the probability distribution phenomenon, while the cross-correlation between two noises(λ), the time delay(τ) and the strength of the feedback loop(K) cause it to disappear; and (ii) the mean first passage time(MFPT) as functions of the noise strengths exhibits a maximum, this maximum is called noise-delayed switching (NDS) of the high concentration state. The NDS phenomenon shows that the noise can modify the stability of a metastable system in a counterintuitive way, the system remains in the metastable state for a longer time compared to the deterministic case. And the τ and the K enhances the stability of the ON state. The physical mechanisms for the switch between the ON and OFF states can be explained from the point of view of the effective potential.

  16. Early visual language exposure and emergent literacy in preschool deaf children: findings from a national longitudinal study.

    Science.gov (United States)

    Allen, Thomas E; Letteri, Amy; Choi, Song Hoa; Dang, Daqian

    2014-01-01

    Brief review is provided of recent research on the impact of early visual language exposure on a variety of developmental outcomes, including literacy, cognition, and social adjustment. This body of work points to the great importance of giving young deaf children early exposure to a visual language as a critical precursor to the acquisition of literacy. Four analyses of data from the Visual Language and Visual Learning (VL2) Early Education Longitudinal Study are summarized. Each confirms findings from previously published laboratory findings and points to the positive effects of early sign language on, respectively, letter knowledge, social adaptability, sustained visual attention, and cognitive-behavioral milestones necessary for academic success. The article concludes with a consideration of the qualitative similarity hypothesis and a finding that the hypothesis is valid, but only if it can be presented as being modality independent.

  17. Trophic level stability-inducing effects of predaceous early juvenile fish in an estuarine mesocosm study.

    Science.gov (United States)

    Wasserman, Ryan J; Noyon, Margaux; Avery, Trevor S; Froneman, P William

    2013-01-01

    Classically, estuarine planktonic research has focussed largely on the physico-chemical drivers of community assemblages leaving a paucity of information on important biological interactions. Within the context of trophic cascades, various treatments using in situ mesocosms were established in a closed estuary to highlight the importance of predation in stabilizing estuarine plankton abundances. Through either the removal (filtration) or addition of certain planktonic groups, five different trophic systems were established. These treatments contained varied numbers of trophic levels and thus different "predators" at the top of the food chain. The abundances of zooplankton (copepod and polychaete), ciliate, micro-flagellate, nano-flagellate and bacteria were investigated in each treatment, over time. The reference treatment containing apex zooplanktivores (early juvenile mullet) and plankton at natural densities mimicked a natural, stable state of an estuary. Proportional variability (PV) and coefficient of variation (CV) of temporal abundances were calculated for each taxon and showed that apex predators in this experimental ecosystem, when compared to the other systems, induced stability. The presence of these predators therefore had consequences for multiple trophic levels, consistent with trophic cascade theory. PV and CV proved useful indices for comparing stability. Apex predators exerted a stabilizing pressure through feeding on copepods and polychaetes which cascaded through the ciliates, micro-flagellates, nano-flagellates and bacteria. When compared with treatments without apex predators, the role of predation in structuring planktonic communities in closed estuaries was highlighted.

  18. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    Science.gov (United States)

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  19. Laser Induced Breakdown Spectroscopy of meteorites as a probe of the early solar system

    Energy Technology Data Exchange (ETDEWEB)

    Dell' Aglio, M., E-mail: marcella.dellaglio@ba.imip.cnr.it [CNR-IMIP, Via Amendola 122/D, 70126 Bari (Italy); De Giacomo, A. [CNR-IMIP, Via Amendola 122/D, 70126 Bari (Italy); Chemistry Department, University of Bari, Via Orabona 4, 70126 Bari (Italy); Gaudiuso, R.; De Pascale, O. [CNR-IMIP, Via Amendola 122/D, 70126 Bari (Italy); Longo, S. [Chemistry Department, University of Bari, Via Orabona 4, 70126 Bari (Italy); INAF-Osservatorio Astrofisico di Arcetri, Largo Enrico Fermi 5, Firenze (Italy)

    2014-11-01

    This paper presents an evaluation of Laser Induced Breakdown Spectroscopy (LIBS) as a technique for gathering data relevant to Solar System geophysics. Two test cases were demonstrated: elemental analysis of chondrules in a chondrite meteorite, and space- resolved analysis of the interface between kamacite and taenite crystals in an octahedrite iron meteorite. In particular most major and minor elements (Fe, Mg, Si, Ti, Al, Cr, Mn, Ca, Fe, Ni, Co) in Sahara 98222 (chondrite) and its chondrules, as well as the profile of Ni content in Toluca (iron meteorite), were determined with the Calibration Free (CF) method. A special attention was devoted to exploring the possibilities offered by variants of the basic technique, such as the use of Fe I Boltzmann distribution as an intensity calibration method of the spectroscopic system, and the use of spatially resolved analysis. - Highlights: • LIBS of meteorites can supply data relevant to the early evolution of solar system. • CF-LIBS was applied to two different test cases. • Chemical identification of chondrules embedded in a chondrite meteorite • Experimental and theoretical profiles of Ni content in an iron meteorite.

  20. Role of MMP-12 on tissue remodeling at early stage of radiation-induced pulmonary injury

    International Nuclear Information System (INIS)

    Li Ming; Song Liangwen; Diao Ruiying; Wang Shaoxia; Xu Xinping; Luo Qingliang

    2008-01-01

    Objective: To explore the role of MMP-12 on tissue remodeling at early stage of radiation- induced pulmonary injury. Methods: Wistar rats irradiated by 60 Co γ-rays to the whole lungs were sacrificed at 1, 2, 4 weeks. MMP-12 mRNA expression was detected by RT-PCR. MMP-2, MMP-9, MMP-12 activities were determined by zymography. The degradation and collapse of elastin were determined by tissue elastin particular staining; the 'cross talking' phenomenon between alveolar type II cells and mesenchymal cells was observed under electron microscope; the expression of TGF-β1 and TNF-α in BALF was detected by ELISA. The expression of α-SMA was determined by immunohistochemistry. Results: The mRNA expression of MMP-12 displayed a significant elevation at 1, 2, 4 weeks after irradiation. MMP-12 activity increased at 2, 4 weeks after irradiation. Elastin began to degrade and collapse at 1 week, which became worst 4 weeks after irradiation. The cross talking phenomenon was found under electron microscope. The expression of TGF-β1, TNF-α and α-SMA was increased gradually as time elapse after irradiation. Conclusions: 60 Co γ-ray irradiation can promote pulmonary MMP-12 expression, initiate pulmonary tissue remodeling by degradation of elastin, and make the pulmonary injury develop towards pulmonary fibrosis eventually. (authors)

  1. Physically based approaches incorporating evaporation for early warning predictions of rainfall-induced landslides

    Science.gov (United States)

    Reder, Alfredo; Rianna, Guido; Pagano, Luca

    2018-02-01

    In the field of rainfall-induced landslides on sloping covers, models for early warning predictions require an adequate trade-off between two aspects: prediction accuracy and timeliness. When a cover's initial hydrological state is a determining factor in triggering landslides, taking evaporative losses into account (or not) could significantly affect both aspects. This study evaluates the performance of three physically based predictive models, converting precipitation and evaporative fluxes into hydrological variables useful in assessing slope safety conditions. Two of the models incorporate evaporation, with one representing evaporation as both a boundary and internal phenomenon, and the other only a boundary phenomenon. The third model totally disregards evaporation. Model performances are assessed by analysing a well-documented case study involving a 2 m thick sloping volcanic cover. The large amount of monitoring data collected for the soil involved in the case study, reconstituted in a suitably equipped lysimeter, makes it possible to propose procedures for calibrating and validating the parameters of the models. All predictions indicate a hydrological singularity at the landslide time (alarm). A comparison of the models' predictions also indicates that the greater the complexity and completeness of the model, the lower the number of predicted hydrological singularities when no landslides occur (false alarms).

  2. Skeletal and dental changes induced by bionator in early treatment of class II

    Directory of Open Access Journals (Sweden)

    Dirceu Barnabé Raveli

    2016-09-01

    Full Text Available The purpose was to investigate the amount of skeletal and dentoalveolar changes after early treatment of Class II, Division 1 malocclusion with bionator appliance in prepubertal growing patients. Forty Class II patients were divided in two groups. Treated group consisted of 20 subjects treated consecutively with bionator. Mean age at the start of treatment (T0 was 9.1 years, while it was 10.6 years at the end of treatment (T1. Mean treatment time was 17.7 months. Pretreatment and post-treatment cephalometric records of treated group were evaluated and compared with a control group consisted of 20 patients with untreated Class II malocclusion. Intergroup comparisons were performed using Student’s t-tests and chi-square test with Yates’ correction at a significance level of 5 per cent. Bionator appliance was effective in generating differential growth between the jaws. Cephalometric skeletal measurements ANB, WITS, Lafh, Co-A and dental L6-Mp, U1.Pp, IsIi, OB, OJ showed statistically significantly different from the control. Bionator induced more dentoalveolar changes than skeletal during treatment in prepubertal stage.

  3. Trophic level stability-inducing effects of predaceous early juvenile fish in an estuarine mesocosm study.

    Directory of Open Access Journals (Sweden)

    Ryan J Wasserman

    Full Text Available Classically, estuarine planktonic research has focussed largely on the physico-chemical drivers of community assemblages leaving a paucity of information on important biological interactions.Within the context of trophic cascades, various treatments using in situ mesocosms were established in a closed estuary to highlight the importance of predation in stabilizing estuarine plankton abundances. Through either the removal (filtration or addition of certain planktonic groups, five different trophic systems were established. These treatments contained varied numbers of trophic levels and thus different "predators" at the top of the food chain. The abundances of zooplankton (copepod and polychaete, ciliate, micro-flagellate, nano-flagellate and bacteria were investigated in each treatment, over time. The reference treatment containing apex zooplanktivores (early juvenile mullet and plankton at natural densities mimicked a natural, stable state of an estuary. Proportional variability (PV and coefficient of variation (CV of temporal abundances were calculated for each taxon and showed that apex predators in this experimental ecosystem, when compared to the other systems, induced stability. The presence of these predators therefore had consequences for multiple trophic levels, consistent with trophic cascade theory.PV and CV proved useful indices for comparing stability. Apex predators exerted a stabilizing pressure through feeding on copepods and polychaetes which cascaded through the ciliates, micro-flagellates, nano-flagellates and bacteria. When compared with treatments without apex predators, the role of predation in structuring planktonic communities in closed estuaries was highlighted.

  4. Emerging technologies to create inducible and genetically defined porcine cancer models

    Directory of Open Access Journals (Sweden)

    Lawrence B Schook

    2016-02-01

    Full Text Available There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research.

  5. An emergency medical communications system by low altitude platform at the early stages of a natural disaster in Indonesia.

    Science.gov (United States)

    Qiantori, Andri; Sutiono, Agung Budi; Hariyanto, Hadi; Suwa, Hirohiko; Ohta, Toshizumi

    2012-02-01

    A natural disaster is a consequence of a natural hazard, such as a tsunami, earthquake or volcanic eruption, affecting humans. In order to support emergency medical communication services in natural disaster areas where the telecommunications facility has been seriously damaged, an ad hoc communication network backbone should be build to support emergency medical services. Combinations of requirements need to be considered before deciding on the best option. In the present study we have proposed a Low Altitude Platform consisting of tethered balloons combined with Wireless Fidelity (WiFi) 802.11 technology. To confirm that the suggested network would satisfy the emergency medical service requirements, a communications experiment, including performance service measurement, was carried out.

  6. Does a pre-hospital emergency pathway improve early diagnosis and referral in suspected stroke patients? – Study protocol of a cluster randomised trial [ISRCTN41456865

    Directory of Open Access Journals (Sweden)

    Lori Giuliano

    2005-10-01

    Full Text Available Abstract Background Early interventions proved to be able to improve prognosis in acute stroke patients. Prompt identification of symptoms, organised timely and efficient transportation towards appropriate facilities, become essential part of effective treatment. The implementation of an evidence based pre-hospital stroke care pathway may be a method for achieving the organizational standards required to grant appropriate care. We performed a systematic search for studies evaluating the effect of pre-hospital and emergency interventions for suspected stroke patients and we found that there seems to be only a few studies on the emergency field and none about implementation of clinical pathways. We will test the hypothesis that the adoption of emergency clinical pathway improves early diagnosis and referral in suspected stroke patients. We designed a cluster randomised controlled trial (C-RCT, the most powerful study design to assess the impact of complex interventions. The study was registered in the Current Controlled Trials Register: ISRCTN41456865 – Implementation of pre-hospital emergency pathway for stroke – a cluster randomised trial. Methods/design Two-arm cluster-randomised trial (C-RCT. 16 emergency services and 14 emergency rooms were randomised either to arm 1 (comprising a training module and administration of the guideline, or to arm 2 (no intervention, current practice. Arm 1 participants (152 physicians, 280 nurses, 50 drivers attended an interactive two sessions course with continuous medical education CME credits on the contents of the clinical pathway. We estimated that around 750 patients will be met by the services in the 6 months of observation. This duration allows recruiting a sample of patients sufficient to observe a 30% improvement in the proportion of appropriate diagnoses. Data collection will be performed using current information systems. Process outcomes will be measured at the cluster level six months after the

  7. Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro

    International Nuclear Information System (INIS)

    Sermsathanasawadi, N.; Inoue, Yoshinori; Iwai, Takehisa; Ishii, Hideto; Yoshida, Masayuki; Igarashi, Kaori; Miura, Masahiko

    2009-01-01

    The effects of ionizing radiation (IR) on tumor neovascularization are still unclear. We previously reported that vascular endothelial cells (ECs) expressing the IR-induced senescence-like (IRSL) phenotype exhibit a significant decrease in angiogenic activity in vitro. In this study, we examined the effects of the IRSL phenotype on adhesion to early endothelial progenitor cells (early EPCs). Adhesion of human peripheral blood-derived early EPCs to human umbilical vein endothelial cells (HUVECs) expressing the IRSL phenotype was evaluated by an adhesion assay under static conditions. It was revealed that the IRSL HUVECs supported significantly more adhesion of early EPCs than normal HUVECs. Expressions of ICAM-1, VCAM-1 and E-selectin were up-regulated in IRSL HUVECs. Pre-treatment of IRSL HUVECs with adhesion-blocking monoclonal antibodies against E-selectin and VCAM-1 significantly reduced early EPC adhesion to IRSL HUVECs, suggesting a potential role for the E-selectin and VCAM-1 in the adhesion between IRSL ECs and early EPCs. Therefore, the IRSL phenotype expressed in ECs may enhance neovascularization via increased homing of early EPCs. Our findings are first to implicate the complex effects of this phenotype on tumor neovascularization following irradiation. (author)

  8. Early changes in microbial colonization selectively modulate intestinal enzymes, but not inducible heat shock proteins in young adult Swine.

    Directory of Open Access Journals (Sweden)

    Marie-Edith Arnal

    Full Text Available Metabolic diseases and obesity are developing worldwide in a context of plethoric intake of high energy diets. The intestine may play a pivotal role due to diet-induced alterations in microbiota composition and increased permeability to bacterial lipopolysaccharide inducing metabolic inflammation. Early programming of metabolic disorders appearing in later life is also suspected, but data on the intestine are lacking. Therefore, we hypothesized that early disturbances in microbial colonization have short- and long-lasting consequences on selected intestinal components including key digestive enzymes and protective inducible heat shock proteins (HSP. The hypothesis was tested in swine offspring born to control mothers (n = 12 or mothers treated with the antibiotic amoxicillin around parturition (n = 11, and slaughtered serially at 14, 28 and 42 days of age to assess short-term effects. To evaluate long-term consequences, young adult offspring from the same litters were offered a normal or a fat-enriched diet for 4 weeks between 140 and 169 days of age and were then slaughtered. Amoxicillin treatment transiently modified both mother and offspring microbiota. This was associated with early but transient reduction in ileal alkaline phosphatase, HSP70 (but not HSP27 and crypt depth, suggesting a milder or delayed intestinal response to bacteria in offspring born to antibiotic-treated mothers. More importantly, we disclosed long-term consequences of this treatment on jejunal alkaline phosphatase (reduced and jejunal and ileal dipeptidylpeptidase IV (increased and decreased, respectively of offspring born to antibiotic-treated dams. Significant interactions between early antibiotic treatment and later diet were observed for jejunal alkaline phosphatase and sucrase. By contrast, inducible HSPs were not affected. In conclusion, our data suggest that early changes in bacterial colonization not only modulate intestinal architecture and function transiently

  9. Romantic Relationship Patterns from Adolescence to Emerging Adulthood: Associations with Family and Peer Experiences in Early Adolescence.

    Science.gov (United States)

    Boisvert, Stéphanie; Poulin, François

    2016-05-01

    The present study identifies and describes romantic relationship patterns from adolescence to adulthood and examines their associations with family and peer experiences in early adolescence. In a 13-year longitudinal study, 281 youth (58 % girls) identified all their romantic partners each year from the ages of 16-24. Dimensions of family relationships (family cohesion, parent-child conflict) and peer relationships (peer likeability, social withdrawal, close friendships, other-sex friendships) were assessed at age 12. Latent class analyses brought out five distinct romantic relationship patterns and significant associations were found with family and peer relationships in early adolescence. These five romantic relationship patterns appeared to follow a continuum of romantic involvement, with romantic relationship patterns situated a both ends of this continuum (later involvement pattern and intense involvement pattern) being associated with more interpersonal experiences in early adolescence.

  10. Hypoperfusion Induced by Preconditioning Treadmill Training in Hyper-Early Reperfusion After Cerebral Ischemia: A Laser Speckle Imaging Study.

    Science.gov (United States)

    He, Zhijie; Lu, Hongyang; Yang, Xiaojiao; Zhang, Li; Wu, Yi; Niu, Wenxiu; Ding, Li; Wang, Guili; Tong, Shanbao; Jia, Jie

    2018-01-01

    Exercise preconditioning induces neuroprotective effects during cerebral ischemia and reperfusion, which involves the recovery of cerebral blood flow (CBF). Mechanisms underlying the neuroprotective effects of re-established CBF following ischemia and reperfusion are unclear. The present study investigated CBF in hyper-early stage of reperfusion by laser speckle contrast imaging, a full-field high-resolution optical imaging technique. Rats with or without treadmill training were subjected to middle cerebral artery occlusion followed by reperfusion. CBF in arteries, veins, and capillaries in hyper-early stage of reperfusion (1, 2, and 3 h after reperfusion) and in subacute stage (24 h after reperfusion) were measured. Neurological scoring and 2,3,5-triphenyltetrazolium chloride staining were further applied to determine the neuroprotective effects of exercise preconditioning. In hyper-early stage of reperfusion, CBF in the rats with exercise preconditioning was reduced significantly in arteries and veins, respectively, compared to rats with no exercise preconditioning. Capillary CBF remained stable in the hyper-early stage of reperfusion, though it increased significantly 24 h after reperfusion in the rats with exercise preconditioning. As a neuroprotective strategy, exercise preconditioning reduced the blood perfusion of arteries and veins in the hyper-early stage of reperfusion, which indicated intervention-induced neuroprotective hypoperfusion after reperfusion onset.

  11. Early predictors of severe acetaminophen-induced hepatotoxicity in a paediatric population referred to a tertiary paediatric department

    DEFF Research Database (Denmark)

    Hedeland, Rikke Lindgaard; Andersen, Jesper; Askbo, Natasha Louise Friis

    2014-01-01

    AIM: The data on severe acetaminophen-induced hepatotoxicity in children are very limited. This study explored the dose-response relationship between ingested acetaminophen and hepatotoxicity, the early biochemical and clinical predictors of hepatotoxicity, the impact of early N-acetylcysteine tr......AIM: The data on severe acetaminophen-induced hepatotoxicity in children are very limited. This study explored the dose-response relationship between ingested acetaminophen and hepatotoxicity, the early biochemical and clinical predictors of hepatotoxicity, the impact of early N......-acetylcysteine treatment on hepatotoxicity and the incidence of nephrotoxicity. METHODS: We carried out a retrospective case study on 25 children aged 11-16 years with severe acetaminophen poisoning. RESULTS: Initial biochemical parameters predicted hepatotoxicity, defined as the maximum levels of the international...... of nephrotoxicity was 12%. There was no significant relationship between the amount of ingested acetaminophen and the degree of hepatotoxicity. CONCLUSION: Paediatric patients at increased risk of severe hepatotoxicity were identified by early biochemical parameters, prehospital vomiting episodes and latency time...

  12. Human Capital and Knowledge Emergence. Induced Effects of the Global Crisis on Human capital and Innovation

    Directory of Open Access Journals (Sweden)

    Simona Buta

    2014-12-01

    Full Text Available In the global crisis context crossed by organizations and countries in the past six years we assist also at conflicting measures in which regards knowledge, innovation and human capital; for example, countries such as England and France have reduced their costs for education, while Germany and other countries (Australia, Austria, Canada and Norway maintained the same allocations for education. What will be the effects of such measures on human capital in the near future? What are the best human resources policies in companies in the crisis context? Given that the subject of the research is "knowledge and human capital", in this paper we refer to the induced effects of the crisis on human capital and innovation. We will also identify the key steps that can be taken during crisis, and not only, to stimulate human capital.

  13. ULTRASTRUCTURAL MODIFICATIONS INDUCED BY DIRECT ACTION OF CU2+ UPON EARLY CHICK EMBRYO

    Directory of Open Access Journals (Sweden)

    Delia Checiu

    2003-01-01

    Full Text Available Teratological testing of sulphonate phtalocyanine (an alimentary blue dye synthetized by the Center of Chemisty, Timisoara, shown a strong malformative effect of this compound upon early chick embryo (48 hours of incubation, (Sandor, Checiu, Prelipceanu, 1985. Dye administration on day 2 of incubation (44-48 hours revealed a high rate of embryo mortality and abnormal modification of caudal segment or even a total absence of caudal tail bud. Living embryos until day 7 of incubation showed a normal development of the anterior body part (head and trunk in contrast with posterior body part which presented an abnormal position of posterior limbs, tail and trunk aplasia. The dye with the some name produced in Germany did not show (in the some experimental conditions a malformative effect. The only difference between the two dyes was the presence of Cu2+ in our compound. It is well known that chemicals and physics factors (X rayes, insuline, hypoxy, D-Actinomycine, sucrose, etc. are noxious, inducing malformations of caudal segment (tail bud, urogenital and anorectal abnormalities associated with cardiac, facial and SNC malformations (Landauer 1953, Shepard 1973. Abnormalities of esophagus, urogenital and anorectal region associated with those of caudal axial skeleton and posterior limb buds are involved in caudal dysplasia syndrome (Duhamel 1961 cited by Roux and Martinet 1962. This syndrome is frequent (1:1000 in children of diabetic mothers (Warkany 1971. Experimental works on mice suggested implication of genetic factors in pathogenesis of this syndrome (Frye et all.1964 cited by Warkany 1971. Previous investigations (Checiu et all. 1966 revealed a caudal malformative syndrome in chick embryos induced by Cu2+. It is well known capacity of some heavy metal ions to affect the formation and desintegration reaction of free radicals. The aim of this paper is to present a morphological study of caudal malformative syndrome (Checiu et all. 1999 and an

  14. Visualization of odor-induced neuronal activity by immediate early gene expression.

    Science.gov (United States)

    Bepari, Asim K; Watanabe, Keisuke; Yamaguchi, Masahiro; Tamamaki, Nobuaki; Takebayashi, Hirohide

    2012-11-05

    Sensitive detection of sensory-evoked neuronal activation is a key to mechanistic understanding of brain functions. Since immediate early genes (IEGs) are readily induced in the brain by environmental changes, tracing IEG expression provides a convenient tool to identify brain activity. In this study we used in situ hybridization to detect odor-evoked induction of ten IEGs in the mouse olfactory system. We then analyzed IEG induction in the cyclic nucleotide-gated channel subunit A2 (Cnga2)-null mice to visualize residual neuronal activity following odorant exposure since CNGA2 is a key component of the olfactory signal transduction pathway in the main olfactory system. We observed rapid induction of as many as ten IEGs in the mouse olfactory bulb (OB) after olfactory stimulation by a non-biological odorant amyl acetate. A robust increase in expression of several IEGs like c-fos and Egr1 was evident in the glomerular layer, the mitral/tufted cell layer and the granule cell layer. Additionally, the neuronal IEG Npas4 showed steep induction from a very low basal expression level predominantly in the granule cell layer. In Cnga2-null mice, which are usually anosmic and sexually unresponsive, glomerular activation was insignificant in response to either ambient odorants or female stimuli. However, a subtle induction of c-fos took place in the OB of a few Cnga2-mutants which exhibited sexual arousal. Interestingly, very strong glomerular activation was observed in the OB of Cnga2-null male mice after stimulation with either the neutral odor amyl acetate or the predator odor 2, 3, 5-trimethyl-3-thiazoline (TMT). This study shows for the first time that in vivo olfactory stimulation can robustly induce the neuronal IEG Npas4 in the mouse OB and confirms the odor-evoked induction of a number of IEGs. As shown in previous studies, our results indicate that a CNGA2-independent signaling pathway(s) may activate the olfactory circuit in Cnga2-null mice and that neuronal

  15. Visualization of odor-induced neuronal activity by immediate early gene expression

    Directory of Open Access Journals (Sweden)

    Bepari Asim K

    2012-11-01

    Full Text Available Abstract Background Sensitive detection of sensory-evoked neuronal activation is a key to mechanistic understanding of brain functions. Since immediate early genes (IEGs are readily induced in the brain by environmental changes, tracing IEG expression provides a convenient tool to identify brain activity. In this study we used in situ hybridization to detect odor-evoked induction of ten IEGs in the mouse olfactory system. We then analyzed IEG induction in the cyclic nucleotide-gated channel subunit A2 (Cnga2-null mice to visualize residual neuronal activity following odorant exposure since CNGA2 is a key component of the olfactory signal transduction pathway in the main olfactory system. Results We observed rapid induction of as many as ten IEGs in the mouse olfactory bulb (OB after olfactory stimulation by a non-biological odorant amyl acetate. A robust increase in expression of several IEGs like c-fos and Egr1 was evident in the glomerular layer, the mitral/tufted cell layer and the granule cell layer. Additionally, the neuronal IEG Npas4 showed steep induction from a very low basal expression level predominantly in the granule cell layer. In Cnga2-null mice, which are usually anosmic and sexually unresponsive, glomerular activation was insignificant in response to either ambient odorants or female stimuli. However, a subtle induction of c-fos took place in the OB of a few Cnga2-mutants which exhibited sexual arousal. Interestingly, very strong glomerular activation was observed in the OB of Cnga2-null male mice after stimulation with either the neutral odor amyl acetate or the predator odor 2, 3, 5-trimethyl-3-thiazoline (TMT. Conclusions This study shows for the first time that in vivo olfactory stimulation can robustly induce the neuronal IEG Npas4 in the mouse OB and confirms the odor-evoked induction of a number of IEGs. As shown in previous studies, our results indicate that a CNGA2-independent signaling pathway(s may activate the

  16. Convention on early notification of a nuclear accident. Convention on assistance in the case of a nuclear accident or radiological emergency

    International Nuclear Information System (INIS)

    1990-08-01

    The document refers to the Convention on Early Notification of a Nuclear Accident (IAEA-INFCIRC-335) and to the Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency (IAEA-INFCIRC-336). Part I contains reservations/declarations made upon or following signature and Part II contains reservations/declarations made upon or following deposit of instrument expressing consent to be bound. The status of signature, ratification, acceptance, approval or accession by States or organizations as of 31 July 1990 is presented in two attachments

  17. Convention on early notification of a nuclear accident. Convention on assistance in the case of a nuclear accident or radiological emergency

    International Nuclear Information System (INIS)

    1989-08-01

    The document refers to the Convention on early notification of a nuclear accident (INFCIRC-335) and to the Convention on assistance in the case of a nuclear accident or radiological emergency (INFCIRC-336). Part I contains reservations/declarations made upon or following signature and Part II contains reservations/declarations made upon or following deposit of instrument expressing consent to be bound. The status of signature, ratification, acceptance, approval or accession by States or organizations as of 31 July 1989 for the conventions is presented in two attachments

  18. Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes.

    Science.gov (United States)

    Li, Wen; Wang, Xianming; Fan, Wenxia; Zhao, Ping; Chan, Yau-Chi; Chen, Shen; Zhang, Shiqiang; Guo, Xiangpeng; Zhang, Ya; Li, Yanhua; Cai, Jinglei; Qin, Dajiang; Li, Xingyan; Yang, Jiayin; Peng, Tianran; Zychlinski, Daniela; Hoffmann, Dirk; Zhang, Ruosi; Deng, Kang; Ng, Kwong-Man; Menten, Bjorn; Zhong, Mei; Wu, Jiayan; Li, Zhiyuan; Chen, Yonglong; Schambach, Axel; Tse, Hung-Fat; Pei, Duanqing; Esteban, Miguel A

    2012-01-01

    Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation.

  19. Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Abdelaziz, Dalia H A; Ali, Sahar A; Mostafa, Mahmoud M A

    2015-06-01

    In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored. The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats. The aqueous suspension of P. dactylifera seeds (aqPDS) (1 g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase. Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248 ± 42 versus 508 ± 60 mg/dl), urea (32 ± 3.3 versus 48.3 ± 5.6 mg/dl), creatinine (2.2 ± 0.35 versus 3.8 ± 0.37 mg/dl), ALT (29.6 ± 3.9 versus 46.4 ± 5.9 IU/l), and AST (73.3 ± 13 versus 127.8 ± 18.7 IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats. The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.

  20. Effectiveness of a Multi-Stage Networked Organisation for Early Integration of Multiple Perspectives on Emerging and Future Crises

    NARCIS (Netherlands)

    Homberg, M.J.C. van den; Pieneman, R.B.J.; Kuijt, J. van de; Berg, P. van den

    2014-01-01

    In the early phase of the crisis spectrum it is particularly challenging to apply a comprehensive approach. Complexities involve how to reach a shared context and conflict analysis, involve the local perspective, have an explicit Theory of Change and how to deal with political sensitivity. Military

  1. Professionalisation in Early Childhood Education: A Comparative View of Emerging Professional Profiles in Germany (Bremen) and Greece

    Science.gov (United States)

    Vrinioti, Kalliope

    2013-01-01

    In this article, a comparative approach is applied to two programmes of study for the education of early childhood pedagogues. One of the terms of our comparison is the University of Bremen's Bachelor of Arts degree in "subject related educational sciences," while the other is the programme offered by Aristotle University of…

  2. Assessing the socio-cultural impacts of emerging molecular technologies for the early diagnosis of Alzheimer’s disease

    NARCIS (Netherlands)

    Boenink, M.; Cuijpers, Y.M.; Laan, A.L. van der; Lente, H. van; Moors, E.H.M.

    2011-01-01

    Novel technologies for early diagnosis of Alzheimer’s disease (AD) will impact the way society views and deals with AD and ageing. However, such “sociocultural” impacts are hardly acknowledged in standard approaches of technology assessment. In this paper, we outline three steps to assess such

  3. Early emergence of adult-like fear renewal in the developing rat after chronic corticosterone treatment of the dam or the pups.

    Science.gov (United States)

    Callaghan, Bridget L; Richardson, Rick

    2014-10-01

    Early adversity increases the risk of nearly all mental health disorders. Although tractable animal models exist to probe the psychobiology of early adversity, the empirical research has focused largely on adult outcomes. In the current studies we examined how early exposure to the stress hormone corticosterone (CORT) affects the maturation of fear extinction in infant rats. Whereas juvenile and adult rodents exhibit extinction learning that is relapse-prone (i.e., they show renewal and reinstatement of extinguished fear), under typical rearing conditions the extinction system in infant rats appears to be relapse-resistant (i.e., extinction leads to a permanent reduction in conditioned fear). In the current studies we tested the hypothesis that chronically exposing infant rats to CORT, either indirectly (through maternal drinking water) or directly (via insertion of an osmotic pump), leads to an early transition into the adult-like extinction system (i.e., evidence of the renewal effect). Although some differences were observed between the 2 methods of CORT exposure, the data showed that infants exposed to CORT via either method exhibited premature emergence of adult-like extinction learning (i.e., they exhibited the renewal effect). The theoretical implications of these findings for typical and abnormal development of emotion learning systems, as well as their practical applications in the context of prevention and treatment of mental health disorders, are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  4. The induced expression of heat shock proteins as a part of the early cellular response to gamma radiation

    International Nuclear Information System (INIS)

    Stankova, K.; Ivanova, K.; Georgieva, R.; Rupova, I.; Boteva, R.

    2008-01-01

    A variety of stressful stimuli including gamma radiation can induce increase in the synthesis of heat shock proteins (Hsp). This family of molecular chaperones includes members with molecular masses ranging from 10 to 150 kDa and has been identified in all organisms from bacteria to humans. Hsp70 chaperones are very important. The present study aimed to characterize the radiation-induced changes in Hsp70 synthesis in human lymphocytes as a part of the early cellular response to gamma irradiation. The expression of Hsp70 was determined with Western blot and the radiation-induced apoptotic changes were registered by staining with fluorescent dyes. Part of the experiments were performed in the presence of the organic solvent DMSO. At low concentrations this reagent shows antioxidant activity and can reduce the level of the radiation-induced oxidant stress which determines the predominant biological effects of the ionizing radiation. Irradiation with 0.5 to 8 Gy caused statistically significant increase in the synthesis of Hsp70 which was strongest after irradiation with 4 Gy. In the range 0.5-2 Gy the enhancement of the radiation-induced synthesis of Hsp70 reached 60%. Our experimental results characterize changes in the Hsp70 synthesis after gamma irradiation as a part of the early cellular stress response in lymphocytes. (authors)

  5. Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

    Science.gov (United States)

    Zhang, S-X; Huang, F; Gates, M; Shen, X; Holmberg, E G

    2016-11-01

    This is a randomized controlled prospective trial with two parallel groups. The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. This study was conducted in SCS Research Center in Colorado, USA. A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

  6. Clinical roundtable monograph: New data in emerging treatment options for chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Morrow, Gary R; Navari, Rudolph M; Rugo, Hope S

    2014-03-01

    Chemotherapy-induced nausea and vomiting (CINV) has long been one of the most troublesome adverse effects of chemotherapy, leading to significant detriments in quality of life and functioning, increased economic costs, and, in some cases, the discontinuation of effective cancer therapy. The past 2 decades have witnessed a dramatic increase in the number of effective antiemetic agents, with the introduction of the serotonin (5-hydroxytryptamine [5-HT₃]) receptor antagonists (ondansetron, granisetron, and palonosetron), the neurokinin-1 (NK₁) receptor antagonists (aprepitant and fosaprepitant), and the identification of other agents that have demonstrated efficacy against CINV, including corticosteroids. These agents often provide excellent control of emesis. Nausea, however, has proven more intractable, particularly in the days after administration of chemotherapy. Newer antiemetic agents under study may provide additional CINV control, particularly against delayed nausea. New agents undergoing review by the US Food and Drug Administration for the prevention of CINV include the novel NK₁ receptor antagonist rolapitant and a fixed-dose combination consisting of the novel NK₁ receptor antagonist netupitant and palonosetron (NEPA). Adherence to clinical practice guidelines has been shown to significantly improve CINV control. As antiemetic therapy continues to evolve, it will be important for clinicians to stay informed of new developments and changes in guidelines.

  7. New and emerging therapeutic options for the management of chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Schwartzberg, Lee S; Rugo, Hope S; Aapro, Matti S

    2015-03-01

    Chemotherapy-induced nausea and vomiting (CINV) remains one of the most challenging adverse events of chemotherapy, and one that has substantial negative effects on patients, clinicians, and the wider health care system. Use of CINV prophylaxis consistent with clinical practice guidelines is essential for attaining optimal CINV control. In recent years, there has been a dramatic improvement in the control of CINV with the introduction of effective antiemetic agents, including the serotonin (5-hydroxytryptamine [5-HT3]) receptor antagonists (ondansetron, granisetron, and palonosetron) and the neurokinin-1 (NK1) receptor antagonists (aprepitant and fosaprepitant). An important benefit of the newer antiemetic agents is their improved ability to control the delayed CINV that can develop in the days after chemotherapy administration. In October 2014, a fixed-dose oral combination containing the novel NK1 receptor antagonist netupitant and palonosetron (NEPA) received approval from the US Food and Drug Administration. The combination of 2 effective antiemetic agents in a single, oral capsule may help simplify CINV management. Ongoing studies are evaluating new CINV approaches (eg, the novel NK1 receptor antagonist rolapitant), as well as the optimal use of existing therapies. Patient education regarding the timing, prevention, and treatment of CINV is another key component of CINV management.

  8. Perturbation-induced emergence of Poisson-like behavior in non-Poisson systems

    International Nuclear Information System (INIS)

    Akin, Osman C; Grigolini, Paolo; Paradisi, Paolo

    2009-01-01

    The response of a system with ON–OFF intermittency to an external harmonic perturbation is discussed. ON–OFF intermittency is described by means of a sequence of random events, i.e., the transitions from the ON to the OFF state and vice versa. The unperturbed waiting times (WTs) between two events are assumed to satisfy a renewal condition, i.e., the WTs are statistically independent random variables. The response of a renewal model with non-Poisson ON–OFF intermittency, associated with non-exponential WT distribution, is analyzed by looking at the changes induced in the WT statistical distribution by the harmonic perturbation. The scaling properties are also studied by means of diffusion entropy analysis. It is found that, in the range of fast and relatively strong perturbation, the non-Poisson system displays a Poisson-like behavior in both WT distribution and scaling. In particular, the histogram of perturbed WTs becomes a sequence of equally spaced peaks, with intensity decaying exponentially in time. Further, the diffusion entropy detects an ordinary scaling (related to normal diffusion) instead of the expected unperturbed anomalous scaling related to the inverse power-law decay. Thus, an analysis based on the WT histogram and/or on scaling methods has to be considered with some care when dealing with perturbed intermittent systems

  9. Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    2017-08-01

    Full Text Available Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease.The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi, but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness.The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African

  10. Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

    Science.gov (United States)

    Laperchia, Claudia; Tesoriero, Chiara; Seke-Etet, Paul F; La Verde, Valentina; Colavito, Valeria; Grassi-Zucconi, Gigliola; Rodgers, Jean; Montague, Paul; Kennedy, Peter G E; Bentivoglio, Marina

    2017-08-01

    Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis.

  11. A DNA vaccine directed against a rainbow trout rhabdovirus induces early protection against a nodavirus challenge in turbot

    DEFF Research Database (Denmark)

    Sommerset, I.; Lorenzen, Ellen; Lorenzen, Niels

    2003-01-01

    A DNA vaccine encoding the envelope glycoprotein from a fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), has previously been shown to induce both early and long time protection against the virus in rainbow trout. Challenge experiments have revealed that the immunity established shortly...... after vaccination is cross-protective against heterologous fish rhabdoviruses. In this study, we show that the DNA vaccine encoding the VHSV glycoprotein also induces early protection against a non-enveloped, positive-sense RNA vir-us belonging to the Nodavirus family, the Atlantic halibut nodavirus...... (AHNV). In a vaccine. efficacy test using juvenile turbot as model fish, the fish injected with the VHSV vaccine were completely protected against a nodavirus challenge performed 8 days post vaccination, while the cumulative mortality in the control group reached 54%. A DNA vaccine carrying the gene...

  12. Reviewing current and emerging antiemetics for chemotherapy-induced nausea and vomiting prophylaxis.

    Science.gov (United States)

    Natale, James J

    2015-01-01

    This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.

  13. Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury

    OpenAIRE

    Zhang, S-x; Huang, F; Gates, M; Shen, X; Holmberg, E G

    2016-01-01

    Study design: This is a randomized controlled prospective trial with two parallel groups. Objectives: The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. Setting: This study was conducted in SCS Research Center in Colorado, USA. Methods: A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25?-mm height setting in femal...

  14. Tikal, Guatemala, and Emergent Maya Civilization: Excavations reveal evidence of early complex-living at a prime Maya Indian site.

    Science.gov (United States)

    Coe, W R

    1965-03-19

    It would be extravagant to claim that these pages have outlined meaningfully the early evolution of Tikal. Data have been provided largely for one excavation locus at a site which, for all its importance, merely has symptomatic value. We cannot claim to have, at present, sufficient material to document satisfyingly the conditions and products of community-wide living at any point in these early times. Present knowledge of Eb and Tzec ceramics and of all the usual archeological correlates (architecture and so on) is disturbingly incomplete. While we do have a good many data on residence throughout much of Preclassic time, considerably more information is needed before a solid evaluation of Preclassic Tikal society can be achieved. One can only hope that pending excavation programs will provide it. Yet, experience shows that probably only a tiny percentage of early cultural remains, regardless of their grandeur and importance at the time, would have survived the constant quest for construction fills to satisfy a seemingly interminable need to build and revamp.

  15. On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles

    Directory of Open Access Journals (Sweden)

    Carlos A.M. Carvalho

    2017-04-01

    Full Text Available Mayaro virus (MAYV is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell.

  16. Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection—The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress

    Science.gov (United States)

    Quryshi, Nabeel; Norwood Toro, Laura E.; Ait-Aissa, Karima; Kong, Amanda; Beyer, Andreas M.

    2018-01-01

    Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mtDNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects. Telomerase, originally discovered to promote cellular proliferation, has recently emerged as a potential mechanism to counteract mitochondrial defects and restore healthy mitochondrial vascular phenotypes. This review details mechanisms currently used to assess cardiovascular damage, such as C-reactive protein (CRP) and troponin levels, while also unearthing recently researched biomarkers, including circulating mtDNA, telomere length and telomerase activity. Further, we explore a potential role of telomerase in the mitigation of mitochondrial reactive oxygen species and maintenance of mtDNA integrity. Telomerase activity presents a promising indicator for the early detection and treatment of chemotherapy-derived cardiac damage. PMID:29534446

  17. Early postnatal vocalizations predict sociability and spatial memory in C57BL/6J mice: Individual differences in behavioral traits emerge early in development.

    Directory of Open Access Journals (Sweden)

    Kaichi Yoshizaki

    Full Text Available The understanding of individual diversity and its link to brain functions is a fundamental issue in neurobiology. Studies in mice have mainly focused on the investigation of behavior traits in adulthood, whereas longitudinal analyses are largely uninvestigated. Here we have conducted systematic behavior tests in individual mice (C57BL6/J, male, comparing phenotypes at early postnatal stages and in adulthood. Each animal showed different scores in individual behavior tests. However, we observed an inverse correlation between repetitive behavior in the Morris water maze test and sociability in the 3-chamber social interaction test; an increase in repetitive behaviors was associated with poor sociability. In longitudinal analyses, the emission of ultrasonic vocalization during maternal separation at postnatal day 6 in pups was correlated positively with sociability and negatively with spatial memory. Our results show a possibility that individual differences in communication between pups and their mother in infancy is a predictive indicator for sociability and cognitive performance as an adult.

  18. Proteomic responses reveal the differential effects induced by cadmium in mussels Mytilus galloprovincialis at early life stages.

    Science.gov (United States)

    Xu, Lanlan; Peng, Xiao; Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng

    2016-08-01

    Cadmium (Cd) has become an important metal contaminant and posed severe risk on the organisms in the coastal environments of the Bohai Sea. Marine mussel Mytilus galloprovincialis is widely distributed along the Bohai coast and consumed as seafood by local residents. Evidences indicate that the early stages of marine organisms are more sensitive to metal contaminants. In this study, we applied two-dimensional electrophoresis-based proteomics to characterize the biological effects of Cd (50 μg L(-1)) in the early life stages (D-shape larval and juvenile) of mussels. The different proteomic responses demonstrated the differential responsive mechanisms to Cd exposure in these two early life stages of mussels. In details, results indicated that Cd mainly induced immune and oxidative stresses in both D-shape larval and juvenile mussels via different pathways. In addition, the significant up-regulation of triosephosphate isomerase and metallothionein confirmed the enhanced energy demand and mobilized detoxification mechanism in D-shape larval mussels exposed to Cd. In juvenile mussels, Cd exposure also induced clear apoptosis. Overall, this work suggests that Cd is a potential immune toxicant to mussel M. galloprovincialis at early life stages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    International Nuclear Information System (INIS)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa; Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E.; Guo, Lining

    2013-01-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  20. The Emergence of Sex Differences in Personality Traits in Early Adolescence: A Cross-Sectional, Cross-Cultural Study

    Science.gov (United States)

    De Bolle, Marleen; De Fruyt, Filip; McCrae, Robert R.; Löckenhoff, Corinna E.; Costa, Paul T.; Aguilar-Vafaie, Maria E.; Ahn, Chang-kyu; Ahn, Hyun-nie; Alcalay, Lidia; Allik, Jüri; Avdeyeva, Tatyana V.; Bratko, Denis; Brunner-Sciarra, Marina; Cain, Thomas R.; Chan, Wayne; Chittcharat, Niyada; Crawford, Jarret T.; Fehr, Ryan; Ficková, Emília; Gelfand, Michele J.; Graf, Sylvie; Gülgöz, Sami; Hřebíčková, Martina; Jussim, Lee; Klinkosz, Waldemar; Knežević, Goran; de Figueroa, Nora Leibovich; Lima, Margarida P.; Martin, Thomas A.; Marušić, Iris; Mastor, Khairul Anwar; Nakazato, Katsuharu; Nansubuga, Florence; Porrata, Jose; Purić, Danka; Realo, Anu; Reátegui, Norma; Rolland, Jean-Pierre; Schmidt, Vanina; Sekowski, Andrzej; Shakespeare-Finch, Jane; Shimonaka, Yoshiko; Simonetti, Franco; Siuta, Jerzy; Szmigielska, Barbara; Vanno, Vitanya; Wang, Lei; Yik, Michelle; Terracciano, Antonio

    2015-01-01

    Although large international studies have found consistent patterns of sex differences in personality traits among adults (i.e., women scoring higher on most facets), less is known about cross-cultural sex differences in adolescent personality and the role of culture and age in shaping them. The present study examines NEO Personality Inventory-3 (NEO-PI-3, McCrae, Costa, & Martin, 2005) informant ratings of adolescents from 23 cultures (N = 4,850) and investigates culture and age as sources of variability in sex differences of adolescents’ personality. The effect for Neuroticism (with females scoring higher than males) begins to take on its adult form around age 14. Girls score higher on Openness to Experience and Conscientiousness at all ages between 12 and 17 years. A more complex pattern emerges for Extraversion and Agreeableness, although by age 17, sex differences for these traits are highly similar to those observed in adulthood. Cross-sectional data suggest that (1) with advancing age, sex differences found in adolescents increasingly converge towards adult patterns with respect to both direction and magnitude; (2) girls display sex-typed personality traits at an earlier age than boys; and (3) the emergence of sex differences was similar across culture. Practical implications of the present findings are discussed. PMID:25603371

  1. The emergence of sex differences in personality traits in early adolescence: A cross-sectional, cross-cultural study.

    Science.gov (United States)

    De Bolle, Marleen; De Fruyt, Filip; McCrae, Robert R; Löckenhoff, Corinna E; Costa, Paul T; Aguilar-Vafaie, Maria E; Ahn, Chang-Kyu; Ahn, Hyun-Nie; Alcalay, Lidia; Allik, Jüri; Avdeyeva, Tatyana V; Bratko, Denis; Brunner-Sciarra, Marina; Cain, Thomas R; Chan, Wayne; Chittcharat, Niyada; Crawford, Jarret T; Fehr, Ryan; Ficková, Emília; Gelfand, Michele J; Graf, Sylvie; Gülgöz, Sami; Hřebíčková, Martina; Jussim, Lee; Klinkosz, Waldemar; Knežević, Goran; Leibovich de Figueroa, Nora; Lima, Margarida P; Martin, Thomas A; Marušić, Iris; Mastor, Khairul Anwar; Nakazato, Katsuharu; Nansubuga, Florence; Porrata, Jose; Purić, Danka; Realo, Anu; Reátegui, Norma; Rolland, Jean-Pierre; Schmidt, Vanina; Sekowski, Andrzej; Shakespeare-Finch, Jane; Shimonaka, Yoshiko; Simonetti, Franco; Siuta, Jerzy; Szmigielska, Barbara; Vanno, Vitanya; Wang, Lei; Yik, Michelle; Terracciano, Antonio

    2015-01-01

    Although large international studies have found consistent patterns of sex differences in personality traits among adults (i.e., women scoring higher on most facets), less is known about cross-cultural sex differences in adolescent personality and the role of culture and age in shaping them. The present study examines the NEO Personality Inventory-3 (McCrae, Costa, & Martin, 2005) informant ratings of adolescents from 23 cultures (N = 4,850), and investigates culture and age as sources of variability in sex differences of adolescents' personality. The effect for Neuroticism (with females scoring higher than males) begins to take on its adult form around age 14. Girls score higher on Openness to Experience and Conscientiousness at all ages between 12 and 17 years. A more complex pattern emerges for Extraversion and Agreeableness, although by age 17, sex differences for these traits are highly similar to those observed in adulthood. Cross-sectional data suggest that (a) with advancing age, sex differences found in adolescents increasingly converge toward adult patterns with respect to both direction and magnitude; (b) girls display sex-typed personality traits at an earlier age than boys; and (c) the emergence of sex differences was similar across cultures. Practical implications of the present findings are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved). (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  2. Ribosomal genes as early targets of cadmium-induced toxicity in Chironomus riparius larvae

    Energy Technology Data Exchange (ETDEWEB)

    Planello, R. [Biologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, Senda del Rey 9, 28040, Madrid (Spain); Martinez-Guitarte, J.L. [Biologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, Senda del Rey 9, 28040, Madrid (Spain); Morcillo, G. [Biologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, Senda del Rey 9, 28040, Madrid (Spain)]. E-mail: gmorcillo@ccia.uned.es

    2007-02-01

    Cadmium is a widespread environmental pollutant that causes severe impacts in organisms. Although the effects of cadmium on aquatic insects have been studied in terms of their toxicity and changes in developmental parameters, little is known about its molecular and genetic effects. We have investigated the alterations in the pattern of gene expression provoked by acute exposure to cadmium in Chironomus riparius Mg. (Diptera, Chironomidae), a sentinel organism widely used in aquatic toxicity testing. The early cytotoxic effects were evaluated using immunocytochemistry and specific fluorescent probes in fourth instar larvae after 12 h of 10 mM cadmium treatments; under these conditions no significant effect on larvae mortality was detected until after 36 h of exposure. The changes in the pattern of gene expression were analysed by means of DNA/RNA hybrid antibodies in the polytene chromosomes from salivary gland cells. A decrease in the activity of the nucleolus is especially remarkable, accompanied by a significant reduction in size and the modification in nucleolar architecture, as shown by FISH. The inhibition of rDNA transcription was further evaluated by Northern blot analysis, which showed a marked decrease in the level of preribosomal rRNA (54% 45S 12 h). However, the BR genes, whose products are the giant polypeptides that constitute the silk-like secretion for constructing housing tubes, remain active. Simultaneously, decondensation and activation take place at some chromosomal regions, especially at the centromeres. The changes observed in the pattern of gene expression do not resemble those found after heat shock or other cell stressors. These data provide the first evidence that cadmium interacts with ribosomal genes and results in a drastic impairment of the functional activity of the nucleolus, an essential organelle for cellular survival. Therefore, the depletion of ribosomes would be a long-term effect of Cd-induced cellular damage. These findings may

  3. Ribosomal genes as early targets of cadmium-induced toxicity in Chironomus riparius larvae

    International Nuclear Information System (INIS)

    Planello, R.; Martinez-Guitarte, J.L.; Morcillo, G.

    2007-01-01

    Cadmium is a widespread environmental pollutant that causes severe impacts in organisms. Although the effects of cadmium on aquatic insects have been studied in terms of their toxicity and changes in developmental parameters, little is known about its molecular and genetic effects. We have investigated the alterations in the pattern of gene expression provoked by acute exposure to cadmium in Chironomus riparius Mg. (Diptera, Chironomidae), a sentinel organism widely used in aquatic toxicity testing. The early cytotoxic effects were evaluated using immunocytochemistry and specific fluorescent probes in fourth instar larvae after 12 h of 10 mM cadmium treatments; under these conditions no significant effect on larvae mortality was detected until after 36 h of exposure. The changes in the pattern of gene expression were analysed by means of DNA/RNA hybrid antibodies in the polytene chromosomes from salivary gland cells. A decrease in the activity of the nucleolus is especially remarkable, accompanied by a significant reduction in size and the modification in nucleolar architecture, as shown by FISH. The inhibition of rDNA transcription was further evaluated by Northern blot analysis, which showed a marked decrease in the level of preribosomal rRNA (54% 45S 12 h). However, the BR genes, whose products are the giant polypeptides that constitute the silk-like secretion for constructing housing tubes, remain active. Simultaneously, decondensation and activation take place at some chromosomal regions, especially at the centromeres. The changes observed in the pattern of gene expression do not resemble those found after heat shock or other cell stressors. These data provide the first evidence that cadmium interacts with ribosomal genes and results in a drastic impairment of the functional activity of the nucleolus, an essential organelle for cellular survival. Therefore, the depletion of ribosomes would be a long-term effect of Cd-induced cellular damage. These findings may

  4. Early epidemiological assessment of the virulence of emerging infectious diseases: a case study of an influenza pandemic.

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    Full Text Available BACKGROUND: The case fatality ratio (CFR, the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR, using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003 with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1 virus infection in the USA and Canada (2009. Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16-4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.

  5. Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells.

    Science.gov (United States)

    Hahn, Nynke E; Musters, René J P; Fritz, Jan M; Pagano, Patrick J; Vonk, Alexander B A; Paulus, Walter J; van Rossum, Albert C; Meischl, Christof; Niessen, Hans W M; Krijnen, Paul A J

    2014-09-01

    Reactive oxygen species (ROS) produced by different NADPH oxidases (NOX) play a role in cardiomyocyte hypertrophy induced by different stimuli, such as angiotensin II and pressure overload. However, the role of the specific NOX isoforms in phenylephrine (PE)-induced cardiomyocyte hypertrophy is unknown. Therefore we aimed to determine the involvement of the NOX isoforms NOX1, NOX2 and NOX4 in PE-induced cardiomyocyte hypertrophy. Hereto rat neonatal cardiomyoblasts (H9c2 cells) were incubated with 100 μM PE to induce hypertrophy after 24 and 48h as determined via cell and nuclear size measurements using digital imaging microscopy, electron microscopy and an automated cell counter. Digital-imaging microscopy further revealed that in contrast to NOX1 and NOX4, NOX2 expression increased significantly up to 4h after PE stimulation, coinciding and co-localizing with ROS production in the cytoplasm as well as the nucleus. Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Dynamically observing the value of the changes of serum sex hormone levels of early pregnancy after drug-induced abortion

    International Nuclear Information System (INIS)

    Zhao Honggang; Dong Hua; Gu Yan; Zhang Zuncheng

    2009-01-01

    Objective: To observe the value of the changes of serum β-human chorionic gonadotropin (β-HCG), estradiol (E), progesterone (P) Levels of early pregnancy after drug-induced abortion dynamically. Methods: Assessing 55 women proved pregnant by urine or blood HCG retrospecticly, who had terminated their pregnancy by mifepristonr and misoprostol. Meanwhile the serum levels of β-HCG, E, P were monitored dynamically. Results: Among the 55 patients, the levels of β-HCG, E and P had significant decreased (t β-HCG =4.845, t E =7.655, t P =11.390, P E =9.089, P P =2.910, P<0.05). Conclusion: Detectint the serum hormone's levels after drug-induced abortion by chemiluminescent immunoassay, we can assess indirectly the value of administration of mifepristone and misoprostol, predict the prolonged vaginal bleeding after drug-induced abortion, and the outcome of the treatment, which determine wether need another curestage. (authors)

  7. Abdominal emergencies during pregnancy.

    Science.gov (United States)

    Bouyou, J; Gaujoux, S; Marcellin, L; Leconte, M; Goffinet, F; Chapron, C; Dousset, B

    2015-12-01

    Abdominal emergencies during pregnancy (excluding obstetrical emergencies) occur in one out of 500-700 pregnancies and may involve gastrointestinal, gynecologic, urologic, vascular and traumatic etiologies; surgery is necessary in 0.2-2% of cases. Since these emergencies are relatively rare, patients should be referred to specialized centers where surgical, obstetrical and neonatal cares are available, particularly because surgical intervention increases the risk of premature labor. Clinical presentations may be atypical and misleading because of pregnancy-associated anatomical and physiologic alterations, which often result in diagnostic uncertainty and therapeutic delay with increased risks of maternal and infant morbidity. The most common abdominal emergencies are acute appendicitis (best treated by laparoscopic appendectomy), acute calculous cholecystitis (best treated by laparoscopic cholecystectomy from the first trimester through the early part of the third trimester) and intestinal obstruction (where medical treatment is the first-line approach, just as in the non-pregnant patient). Acute pancreatitis is rare, usually resulting from trans-ampullary passage of gallstones; it usually resolves with medical treatment but an elevated risk of recurrent episodes justifies laparoscopic cholecystectomy in the 2nd trimester and endoscopic sphincterotomy in the 3rd trimester. The aim of the present work is to review pregnancy-induced anatomical and physiological modifications, to describe the main abdominal emergencies during pregnancy, their specific features and their diagnostic and therapeutic management. Copyright © 2015. Published by Elsevier Masson SAS.

  8. Death is swallowed up in victory : scenes of death in early Christian art and the emergence of crucifixion iconography

    Directory of Open Access Journals (Sweden)

    McGowan, Felicity Harley

    2011-01-01

    Full Text Available Christianity, and the instrument of Jesus’ death, the cross, remains the pivotal, and universally recognised, symbol of the Christian Church. Yet pictorial representations of the death of Jesus are conspicuously rare in the earliest Christian art. Moreover, the earliest surviving images of Jesus’ Crucifixion do not depict him dead on the cross, but defiantly alive – a visual interpretation of the event that incorporates both the means of his execution and his subsequent victory over death in the Resurrection. This article examines the iconography of a small ivory plaque, carved in Rome in the early fifth century, whereon the Crucifixion is juxtaposed with the suicide of Jesus’ betrayer, Judas Iscariot (Matthew 27 3:5 to effect a powerful visual interpretation of Jesus’ death. As the earliest surviving visual narration of Jesus’ Crucifixion and Resurrection, the ivory will be shown to preserve critical information regarding the interpretation of Christ’s death in the early Christian church - incorporating symbols and visual motifs from pagan funerary sculpture, while illustrating the development of a specifically Christian visual language for the representation of Jesus’ death.

  9. Death is Swallowed Up in Victory: Scenes of Death in Early Christian Art and the Emergence of Crucifixion Iconography

    Directory of Open Access Journals (Sweden)

    Felicity Harley McGowan

    2011-03-01

    Full Text Available Christianity, and the instrument of Jesus’ death, the cross, remains the pivotal, and universally recognised, symbol of the Christian Church. Yet pictorial representations of the death of Jesus are conspicuously rare in the earliest Christian art. Moreover, the earliest surviving images  of Jesus’ Crucifixion do not depict  him dead on the cross, but defiantly alive – a visual interpretation of the event that incorporates both the means of his execution and his subsequent victory over death in the Resurrection. This article examines the iconography of a small ivory plaque, carved in Rome in the early fifth century, whereon the Crucifixion is juxtaposed with the suicide of Jesus’ betrayer, Judas Iscariot (Matthew 27 3:5 to effect a powerful visual interpretation of Jesus’ death. As the earliest surviving visual narration of Jesus’ Crucifixion and Resurrection, the ivory will be shown to preserve critical information regarding the interpretation of Christ’s death in the early Christian church - incorporating symbols and visual motifs from pagan funerary sculpture, while illustrating the development of a specifically Christian visual language for the representation of Jesus’ death.

  10. Interferon-inducible protein 10 (IP-10) is associated with viremia of early HIV-1 infection in Korean patients.

    Science.gov (United States)

    Lee, SoYong; Chung, Yoon-Seok; Yoon, Cheol-Hee; Shin, YoungHyun; Kim, SeungHyun; Choi, Byeong-Sun; Kim, Sung Soon

    2015-05-01

    Cytokines/chemokines play key roles in modulating disease progression in human immunodeficiency virus (HIV) infection. Although it is known that early HIV-1 infection is associated with increased production of proinflammatory cytokines, the relationship between cytokine levels and HIV-1 pathogenesis is not clear. The concentrations of 18 cytokines/chemokines in 30 HIV-1 negative and 208 HIV-1 positive plasma samples from Korean patients were measured by the Luminex system. Early HIV-1 infection was classified according to the Fiebig stage (FS) based on the characteristics of the patients infected with HIV-1. Concentrations of interleukin-12 (IL-12), interferon-inducible protein-10 (IP-10), macrophage inflammatory protein-1α (MIP-1α) and regulated upon activation, normal T cells expressed and secreted (RANTES) were increased significantly during the early stage of HIV-1 infection (FS II-IV) compared with the HIV-1-negative group. Of these cytokines, an elevated level of IP-10 was the only factor to be correlated positively with a higher viral load during the early stages of HIV-1 infection (FS II-IV) in Koreans (R = 0.52, P IP-10 may be an indicator for HIV-1 viremia and associated closely with viral replication in patients with early HIV-1 infection. © 2015 Wiley Periodicals, Inc.

  11. A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Christina Marie Gutierrez

    2015-11-01

    Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.

  12. Federal Financial Incentives to Induce Early Experience Producing Unconventional Liquid Fuels

    National Research Council Canada - National Science Library

    Camm, Frank; Bartis, James T; Bushman, Charles J

    2008-01-01

    ... that is likely to ensure that early CTL production experience occurs cost effectively. Such a relationship yields investor and government behavior that, in turn, generates a set of cash flows to and from...

  13. The Effect of New Collision-Induced Absorption Coefficients on the Early Mars Limit Cycle Hypothesis

    Science.gov (United States)

    Hayworth, B. P.; Payne, R. C.; Kasting, J. F.

    2017-11-01

    Updating the Limit Cycling (LC) Model for early Mars with new absorption coefficients to test for changes to LC behavior and to potentially lower needed concentrations of greenhouse gases. Thought will be given to the effect of LC on habitability.

  14. Federal Financial Incentives to Induce Early Experience Producing Unconventional Liquid Fuels

    National Research Council Canada - National Science Library

    Camm, Frank; Bartis, James T; Bushman, Charles J

    2008-01-01

    This technical report explains an analytic way to design and assess packages of financial incentives that the government can use to cost effectively promote early experience with coal-to-liquids (CTL...

  15. Study on the early and late mutants of radiation induced rice

    International Nuclear Information System (INIS)

    Yang Hefeng; Chen Xiulan; He Zhentian; Gu Shiliang; Xu Chenwu

    1990-12-01

    After three years of consecutive experiments for the irradiated M 2 generations of 53 different varieties of rice, the following results have been obtained: (1) The average of early mutant plant rate is 1.4%. The rate in the early-maturing varieties is lower than that in the late-maturing varieties. It is in proportion to the length of growing period of these varieties tested. The shortened days of growing period of early mutants are 3 to 32 days (the average was 9.5 days), and it is increasing as the growing period increases. (2) In the irradiated M 2 generation of same variety, the early mutants and late mutants could be simultaneously happened, but the rate of the late mutants is 2.67%, which is higher than the rate of early mutants (1.39%). The shortened and prolonged days of growing period are 11.5 and 10.5 days respectively. These early and late mutants have some changes, both good and bad, in agronomical traits such as plant height, weight per kilo-grains and grains number per tassel. In some extent these changes are significant

  16. Early Steroid-Induced Osteonecrosis of Rabbit Femoral Head and Panax notoginseng Saponins: Mechanism and Protective Effects

    Directory of Open Access Journals (Sweden)

    Hui Qiang

    2015-01-01

    Full Text Available Background. This study was aimed at investigating the pathogenesis of oxidative stress in steroid-induced avascular necrosis of the femoral head (SANFH and at exploring the mechanism and protective effects of Panax notoginseng saponins (PNS on early SANFH. Methods. 80 adult New Zealand rabbits were randomly divided into control group, model group, and PNS group. In model group, equine serum was injected into auricular vein; then methylprednisolone was injected into gluteus. In PNS group, PNS was applied for 14 consecutive days before methylprednisolone management. At different time points, serum and femoral heads were prepared for T-AOC, SOD, GSH-PX, ·OH, and MDA determination. Two weeks after steroid management, all femoral heads were assessed with MRI and HE staining. Results. Typical early osteonecrosis symptoms were observed in model group. Our results showed that PNS could significantly ameliorate the decrease of T-AOC level, improve SOD and GSH-PX activity, suppress ·OH ability, and augment MDA level. Besides, PNS improved MRI and pathological changes of the femoral head, markedly reducing the incidence of osteonecrosis. Conclusion. Based on our research, we found oxidative stress played a positive role in the occurrence of SANFH where reactive oxygen species was the direct cause. PNS could protect rabbits against early steroid-induced osteonecrosis of femoral head by its antioxidative effect.

  17. Evolution of herbivore-induced early defense signaling was shaped by genome-wide duplications inNicotiana.

    Science.gov (United States)

    Zhou, Wenwu; Brockmöller, Thomas; Ling, Zhihao; Omdahl, Ashton; Baldwin, Ian T; Xu, Shuqing

    2016-11-04

    Herbivore-induced defenses are widespread, rapidly evolving and relevant for plant fitness. Such induced defenses are often mediated by early defense signaling (EDS) rapidly activated by the perception of herbivore associated elicitors (HAE) that includes transient accumulations of jasmonic acid (JA). Analyzing 60 HAE-induced leaf transcriptomes from closely-related Nicotiana species revealed a key gene co-expression network (M4 module) which is co-activated with the HAE-induced JA accumulations but is elicited independently of JA, as revealed in plants silenced in JA signaling. Functional annotations of the M4 module were consistent with roles in EDS and a newly identified hub gene of the M4 module (NaLRRK1) mediates a negative feedback loop with JA signaling. Phylogenomic analysis revealed preferential gene retention after genome-wide duplications shaped the evolution of HAE-induced EDS in Nicotiana . These results highlight the importance of genome-wide duplications in the evolution of adaptive traits in plants.

  18. Emergence of complex behavior in pili-based motility in early stages of P. aeruginosa surface adaptation

    Science.gov (United States)

    Brill-Karniely, Yifat; Jin, Fan; Wong, Gerard C. L.; Frenkel, Daan; Dobnikar, Jure

    2017-04-01

    Pseudomonas aeruginosa move across surfaces by using multiple Type IV Pili (TFP), motorized appendages capable of force generation via linear extension/retraction cycles, to generate surface motions collectively known as twitching motility. Pseudomonas cells arrive at a surface with low levels of piliation and TFP activity, which both progressively increase as the cells sense the presence of a surface. At present, it is not clear how twitching motility emerges from these initial minimal conditions. Here, we build a simple model for TFP-driven surface motility without complications from viscous and solid friction on surfaces. We discover the unanticipated structural requirement that TFP motors need to have a minimal amount of effective angular rigidity in order for cells to perform the various classes of experimentally-observed motions. Moreover, a surprisingly small number of TFP are needed to recapitulate movement signatures associated with twitching: Two TFP can already produce movements reminiscent of recently observed slingshot type motion. Interestingly, jerky slingshot motions characteristic of twitching motility comprise the transition region between different types of observed crawling behavior in the dynamical phase diagram, such as self-trapped localized motion, 2-D diffusive exploration, and super-diffusive persistent motion.

  19. The emergence of modern type rain forests and mangroves and their traces in the palaeobotanical record during the Late Cretaceous and early Tertiary

    Science.gov (United States)

    Mohr, Barbara; Coiffard, Clément

    2014-05-01

    The origin of modern rain forests is still very poorly known. This ecosystem could have potentially fully evolved only after the development of relatively high numbers of flowering plant families adapted to rain forest conditions. During the early phase of angiosperm evolution in the early Cretaceous the palaeo-equatorial region was located in a seasonally dry climatic belt, so that during this phase, flowering plants often show adaptations to drought, rather than to continuously wet climate conditions. Therefore it is not surprising that except for the Nymphaeales, the most basal members of extant angiosperm families have members that do not necessarily occur in the continuously wet tropics today. However, during the late Early Cretaceous several clades emerged that later would give rise to families that are typically found today mostly in (shady) moist places in warmer regions. This is especially seen among the monocotyledons, a group of the mesangiosperms, that developed in many cases large leaves often with very specific venation patterns that make these leaves very unique and well recognizable. Especially members of three groups are here of interest: the arum family (Araceae), the palms (Arecaceae) and the Ginger and allies (Zingiberales). The earliest fossil of Araceae are restricted to low latitudes during the lower Cretaceous. Arecaceae and Zingiberales do not appear in the fossil record before the early late Cretaceous and occur at mid latitudes. During the Late Cretaceous, Araceae are represented at mid latitudes by non-tropical early diverging members and at low latitudes by derived rainforest members. Palms became widespread during the Late Cretataceous and also Nypa, a typical element of tropical to subtropical mangrove environments evolved during this time period. During the Paleocene Arecaceae appear to be restricted to lower latitudes as well as Zingiberales. All three groups are again widespread during the Eocene, reaching higher latitudes and

  20. Convention of early notification of a nuclear accident. Convention of assistance in the case of a nuclear accident or radiological emergency

    International Nuclear Information System (INIS)

    1988-05-01

    The document refers to the Convention on early notification of a nuclear accident (INFCIRC-335) and to the Convention on assistance in the case of a nuclear accident or radiological emergency (INFCIRC-336). Part I of the document contains reservations/declarations made upon or following signature made by Algeria, Iraq and Thailand. Part II contains reservations/declarations made upon or following deposit of instrument expressing consent to be bound made by Australia, Bulgaria, China, India, Japan, Malaysia, Mongolia, Poland, South Africa, United Arab Emirates and Socialist Republic of Viet Nam. The status of signature, notification, acceptance, approval or accession of the two conventions as of 13 May 1988 is presented in two attachments

  1. A novel emergency department based prevention intervention program for people living with HIV: evaluation of early experiences

    Directory of Open Access Journals (Sweden)

    Trott Alexander T

    2007-10-01

    Full Text Available Abstract Background HIV prevention is increasingly focused on people living with HIV (PLWH and the role of healthcare settings in prevention. Emergency Departments (EDs frequently care for PLWH, but do not typically endorse a prevention mission. We conducted a pilot exploratory evaluation of the first reported ED program to address the prevention needs of PLWH. Methods This retrospective observational cohort evaluation reviewed program records to describe the first six months of participants and programmatic operation. Trained counselors provided a risk assessment and counseling intervention combined with three linkage interventions: i linkage to health care, ii linkage to case management, and iii linkage to partner counseling and referral. Results Of 81 self-identified PLWH who were approached, 55 initially agreed to participate. Of those completing risk assessment, 17/53 (32%, 95 CI 20% to 46% reported unprotected anal/vaginal intercourse or needle sharing in the past six months with a partner presumed to be HIV negative. Counseling was provided to 52/53 (98%. For those requesting services, 11/15 (73% were linked to healthcare, 4/23 (17% were coordinated with case management, and 1/4 (25% completed partner counseling and referral. Conclusion Given base resources of trained counselors, it was feasible to implement a program to address the prevention needs for persons living with HIV in an urban ED. ED patients with HIV often have unmet needs which might be addressed by improved linkage with existing community resources. Healthcare and prevention barriers for PLWH may be attenuated if EDs were to incorporate CDC recommended prevention measures for healthcare providers.

  2. Studies on some agronomic and quality characteristics of 271 induced early mutants of rice (Oryza sativa L. cv. Nizersail)

    International Nuclear Information System (INIS)

    Rahman, Mostafizur; Miah, A.J.; Mansur, M.A.; Kaul, A.K.

    1980-01-01

    Nizersail, the most popular, recommended rice variety in Bangladesh, was subjected to gamma-irradiation (10 - 25 kR) or ethyl methane sulfonate (EMS) (0.75 - 1.50%) treatments to obtain the mutants with stiff straw and early maturity. In the M 2 generation, 29 gamma-ray- and 8 EMS-induced mutants were selected mainly for short culm length and earliness. Further selections were made in the segregating M 3 and M 4 populations, and finally 400 plants with short culm length were obtained. These 400 selections were grown in M 5 lines, and 271 of these lines were analyzed for several characters. Heading time had singificantly shifted towards earliness in 40 lines. Yield per plant, 1,000-kernel weight, the length/breadth ratio of kernels, alkali spreading index value (indicator of amylose content) and dye-binding capacity (indicator of protein content) were significantly higher than those in the mother variety in 10 - 30% of the lines examined. However, no positive correlation among these characters was observed. Significant negative correlations were observed between heading time and 1,000-kernel weight, and between yield per plant and dye-binding capacity. These results suggest that the early heading plants may produce fewer tillers with bolder seeds, and that high yielding types may not simultaneously show high protein content. (Kaihara, S.)

  3. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    Science.gov (United States)

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

  4. Early Life and Postnatal Western Diet Feeding and Susceptibility to Chemically Induced Colonic Aberrant Crypt Foci in Male Rats Offspring.

    Science.gov (United States)

    Lopes, Gisele Aparecida Dionísio; Dias, Marcos Correa; Barbisan, Luís Fernando; Marchesan Rodrigues, Maria Aparecida

    2016-07-01

    The modifying effects of a Western diet (WD) during early life on the susceptibility to colon carcinogenesis induced by dimethylhydrazine (DMH) were examined in male rats as later adults. Three groups were studied: a lifetime control diet-fed group, a test group fed WD since pregnancy from dams until postnatal day (PND) 42, and a group fed WD at adulthood. At PND 70, all groups received the carcinogen DMH and were euthanized 10 wk later. Colonic aberrant crypt foci (ACF) were scored (number and crypt multiplicity) and the altered pattern of β-catenin expression was evaluated in the colonic lesions. ACF multiplicity (≥4 crypts) was significantly higher in the group fed WD at early life than in the group fed the control diet. ACF number, crypt multiplicity, and the number of high-grade dysplastic lesions were significantly higher in the group fed WD at adulthood than in the groupfed the control diet. The number of lesions with altered β-catenin expression was higher in the groups receiving WD at early life or at adulthood than in the lifetime control-diet-fed group. These findings indicate that WD exposure at early life increased the susceptibility to colon carcinogenesis at adulthood.

  5. Cytogenetic analysis of thymocytes during early stages after irradiation in mice with different susceptibilities to radiation-induced lymphomagenesis

    International Nuclear Information System (INIS)

    Chen Ying; Kubo, Eiko; Sado, Toshihiko; Muto, Masahiro.

    1996-01-01

    To investigate the relationship between radiation-induced chromosomal instability and lymphomagenesis, the incidences of chromosome aberrations and of cells with abnormal chromosome complements in the thymuses of B10. Thy 1.1 and STS/A strains which have shown marked differences in susceptibility to radiation-induced lymphomagenesis were compared at an early time (12-33 days) after whole-body X-irradiation (1.61 Gy X 4). Numerical and structural aberrations of chromosome in B10. Thy 1.1 mice were higher than those in STS/A mice. The average incidence of trisomy 15 was 37.5% (12/32 mice) from 12 days to 32 days after irradiation in B10. Thy 1.1 mice, whereas none was found (0/38 mice) in STS/A mice. Frequencies of aberrations in chromosomes 11, 12, 15 of the thymocytes from irradiated B10. Thy 1.1 mice were higher than those from irradiated STS/A mice, and especially, the most frequent translocations occurred in the E-F regions of chromosome 12. Using B10. Thy 1 congenic mice, we found that in many cases (8/13), the chromosome aberrations detected in the thymocytes from B10. Thy 1.1 mice at an early time after irradiation could also be observed in the donor-type (Thy 1.1) lymphomas developed from recipient mice 4-5 months after intrathymic injection, suggesting that these chromosome aberrations have some role in lymphomagenesis. The difference of chromosome instability detected at an early time after irradiation might be due to genetic background with regard to genomic instability induced by radiation. (author)

  6. Early Stage of Origin of Earth (interval after Emergence of Sun, Formation of Liquid Core, Formation of Solid Core)

    Science.gov (United States)

    Pechernikova, G. V.; Sergeev, V. N.

    2017-05-01

    Gravitational collapse of interstellar molecular cloud fragment has led to the formation of the Sun and its surrounding protoplanetary disk, consisting of 5 × 10^5 dust and gas. The collapse continued (1 years. Age of solar system (about 4.57×10^9 years) determine by age calcium-aluminum inclusions (CAI) which are present at samples of some meteorites (chondrites). Subsidence of dust to the central plane of a protoplanetary disk has led to formation of a dust subdisk which as a result of gravitational instability has broken up to condensations. In the process of collisional evolution they turned into dense planetesimals from which the planets formed. The accounting of a role of large bodies in evolution of a protoplanetary swarm in the field of terrestrial planets has allowed to define times of formation of the massive bodies permitting their early differentiation at the expense of short-lived isotopes heating and impacts to the melting temperature of the depths. The total time of Earth's growth is estimated about 10^8 years. Hf geochronometer showed that the core of the Earth has existed for Using W about 3×10^7 Hf geohronometer years since the formation of the CAI. Thus data W point to the formation of the Earth's core during its accretion. The paleomagnetic data indicate the existence of Earth's magnetic field past 3.5×10^9 years. But the age of the solid core, estimated by heat flow at the core-mantle boundary is 1.7×10^9 (0.5 years). Measurements of the thermal conductivity of liquid iron under the conditions that exist in the Earth's core, indicate the absence of the need for a solid core of existence to support the work geodynamo, although electrical resistivity measurements yield the opposite result.

  7. Exploring the Potential of a Global Emerging Contaminant Early Warning Network through the Use of Retrospective Suspect Screening with High-Resolution Mass Spectrometry.

    Science.gov (United States)

    Alygizakis, Nikiforos A; Samanipour, Saer; Hollender, Juliane; Ibáñez, María; Kaserzon, Sarit; Kokkali, Varvara; van Leerdam, Jan A; Mueller, Jochen F; Pijnappels, Martijn; Reid, Malcolm J; Schymanski, Emma L; Slobodnik, Jaroslav; Thomaidis, Nikolaos S; Thomas, Kevin V

    2018-04-13

    A key challenge in the environmental and exposure sciences is to establish experimental evidence of the role of chemical exposure in human and environmental systems. High resolution and accurate tandem mass spectrometry (HRMS) is increasingly being used for the analysis of environmental samples. One lauded benefit of HRMS is the possibility to retrospectively process data for (previously omitted) compounds that has led to the archiving of HRMS data. Archived HRMS data affords the possibility of exploiting historical data to rapidly and effectively establish the temporal and spatial occurrence of newly identified contaminants through retrospective suspect screening. We propose to establish a global emerging contaminant early warning network to rapidly assess the spatial and temporal distribution of contaminants of emerging concern in environmental samples through performing retrospective analysis on HRMS data. The effectiveness of such a network is demonstrated through a pilot study, where eight reference laboratories with available archived HRMS data retrospectively screened data acquired from aqueous environmental samples collected in 14 countries on 3 different continents. The widespread spatial occurrence of several surfactants (e.g., polyethylene glycols ( PEGs ) and C12AEO-PEGs ), transformation products of selected drugs (e.g., gabapentin-lactam, metoprolol-acid, carbamazepine-10-hydroxy, omeprazole-4-hydroxy-sulfide, and 2-benzothiazole-sulfonic-acid), and industrial chemicals (3-nitrobenzenesulfonate and bisphenol-S) was revealed. Obtaining identifications of increased reliability through retrospective suspect screening is challenging, and recommendations for dealing with issues such as broad chromatographic peaks, data acquisition, and sensitivity are provided.

  8. Cholinergic intrapancreatic neurons induce Ca²+ signaling and early-response gene expression in pancreatic acinar cells.

    Science.gov (United States)

    Turner, D J; cowles, R A; Segura, B J; Romanchuk, G; Barnhart, D C; Mulholland, M W

    2000-01-01

    Pancreatic exocrine function has been demonstrated to be under neuronal regulation. The pathways responsible for this effect, and the long-term consequences of such interactions, are incompletely described. The effects of neuronal depolarization on pancreatic acinar cells were studied to determine whether calcium signaling and c-fos expression were activated. In pancreatic lobules, which contain both neurons and acinar cells, agonists that selectively stimulated neurons increased intracellular calcium in acinar cells. Depolarization also led to the expression of c-fos protein in 24% +/- 4% of the acinar cells. In AR42J pancreatic acinar cells, cholinergic stimulation demonstrated an average increase of 398 +/- 19 nmol/L in intracellular calcium levels, and induced c-fos expression that was time and dose dependent. The data indicate that intrapancreatic neurons induce Ca²+ signaling and early-response gene expression in pancreatic acinar cells.

  9. Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

    DEFF Research Database (Denmark)

    Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

    2008-01-01

    ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice. METHODS: COMP......-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti......-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay. RESULTS: COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were...

  10. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

    Directory of Open Access Journals (Sweden)

    Cristina Herrera

    2016-04-01

    Full Text Available The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM and other extracellular matrix (ECM proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

  11. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

    Science.gov (United States)

    Herrera, Cristina; Macêdo, Jéssica Kele A; Feoli, Andrés; Escalante, Teresa; Rucavado, Alexandra; Gutiérrez, José María; Fox, Jay W

    2016-04-01

    The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM) and other extracellular matrix (ECM) proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs) or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

  12. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  13. Short-Term Second Language and Music Training Induces Lasting Functional Brain Changes in Early Childhood

    Science.gov (United States)

    Moreno, Sylvain; Lee, Yunjo; Janus, Monika; Bialystok, Ellen

    2015-01-01

    Immediate and lasting effects of music or second-language training were examined in early childhood using event-related potentials. Event-related potentials were recorded for French vowels and musical notes in a passive oddball paradigm in thirty-six 4- to 6-year-old children who received either French or music training. Following training, both…

  14. Photo-induced toxicity in early life stage fiddler crab (Uca longisignalis) following exposure to Deepwater Horizon oil.

    Science.gov (United States)

    Damare, Leigh M; Bridges, Kristin N; Alloy, Matthew M; Curran, Thomas E; Soulen, Brianne K; Forth, Heather P; Lay, Claire R; Morris, Jeffrey M; Stoeckel, James A; Roberts, Aaron P

    2018-02-20

    The 2010 explosion of the Deepwater Horizon (DWH) oil rig led to the release of millions of barrels of oil in the Gulf of Mexico. Oil in aquatic ecosystems exerts toxicity through multiple mechanisms, including photo-induced toxicity following co-exposure with UV radiation. The timing and location of the spill coincided with both fiddler crab reproduction and peak yearly UV intensities, putting early life stage fiddler crabs at risk of injury due to photo-induced toxicity. The present study assessed sensitivity of fiddler crab larvae to photo-induced toxicity during co-exposure to a range of environmentally relevant dilutions of high-energy water accommodated fractions of DWH oil, and either filters that allowed for variable UV penetration. Solar exposures (duration: 7-h per day) were conducted for two consecutive days, with a dark recovery period (duration: 17-h) in between. Survival was significantly decreased in treatments the presence of >10% UV and relatively low concentrations of oil. Results of the present study indicate fiddler crab larvae are sensitive to photo-induced toxicity in the presence of DWH oil. These results are of concern, as fiddler crabs play an important role as ecosystem engineers, modulating sediment biogeochemical processes via burrowing action. Furthermore, they occupy an important place in the food web in the Gulf of Mexico.

  15. Chronic morphine treatment enhances sciatic nerve stimulation-induced immediate early gene expression in the rat dorsal horn.

    Science.gov (United States)

    Bojovic, Ognjen; Bramham, Clive R; Tjølsen, Arne

    2015-01-01

    Synaptic plasticity is a property of neurons that can be induced by conditioning electrical stimulation (CS) of afferent fibers in the spinal cord. This is a widely studied property of spinal cord and hippocampal neurons. CS has been shown to trigger enhanced expression of immediate early gene proteins (IEGPs), with peak increases observed 2 hour post stimulation. Chronic morphine treatment has been shown to promoteinduce opioid-induced hyperalgesia, and also to increase CS-induced central sensitization in the dorsal horn. As IEGP expression may contribute to development of chronic pain states, we aimed to determine whether chronic morphine treatment affects the expression of IEGPs following sciatic nerve CS. Changes in expression of the IEGPs Arc, c-Fos or Zif268 were determined in cells of the lumbar dorsal horn of the spinal cord. Chronic Morphine pretreatment over 7 days led to a significant increase in the number of IEGP positive cells observed at both 2 h and 6 h after CS. The same pattern of immunoreactivity was obtained for all IEGPs, with peak increases occurring at 2 h post CS. In contrast, morphine treatment alone in sham operated animals had no effect on IEGP expression. We conclude that chronic morphine treatment enhances stimulus-induced expression of IEGPs in the lumbar dorsal horn. These data support the notion that morphine alters gene expression responses linked to nociceptive stimulation and plasticity.

  16. Perillyl Alcohol Protects against Fe-NTA-Induced Nephrotoxicity and Early Tumor Promotional Events in Rat Experimental Model

    Directory of Open Access Journals (Sweden)

    Tamanna Jahangir

    2007-01-01

    Full Text Available Plants have been widely used as protective agents against a wide variety of processes and compounds that damage tissues via free radical mechanisms. Perillyl alcohol (PA is a naturally occurring monoterpene found in the essential oils of numerous species of plants including mints, cherries and celery seeds. This monocyclic monoterpene has shown antioxidant and therapeutic activity in various studies against various xenobiotics. In this study, we have analyzed the effects of PA against single intraperitoneal dose of ferric nitrilotriacetate (Fe-NTA (9 mg iron per kg body weight-induced nephrotoxicity and early tumor promotional events. The pretreatment of Fe-NTA-treated rats with 0.5% per kg body weight dose and 1% per kg body weight dose of PA for seven consecutive days significantly reversed the Fe-NTA-induced malondialdehyde formation, xanthine oxidase activity (P < 0.001, ornithine decarboxylase activity (P < 0.001 and 3[H]thymidine incorporation in renal DNA (P < 0.001 with simultaneous significant depletion in serum toxicity markers blood urea nitrogen and creatinine (P < 0.001. Significant restoration at both the doses was recorded in depleted renal glutathione content, and its dependent enzymes with prophylactic treatment of PA. Present results suggest that PA potentially attenuates against Fe-NTA-induced oxidative damage and tumor promotional events that preclude its development as a future drug to avert the free radical-induced toxicity.

  17. Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Streb

    2011-04-01

    Full Text Available Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β in cultured smooth muscle cells (SMC as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall.

  18. Combined determination of highly sensitive troponin T and copeptin for early exclusion of acute myocardial infarction: first experience in an emergency department of a general hospital

    Directory of Open Access Journals (Sweden)

    Lotze U

    2011-08-01

    Full Text Available Ulrich Lotze1, Holger Lemm2, Anke Heyer2, Karin Müller31Department of Internal Medicine, German Red Cross Hospital Sondershausen, Sondershausen, 2Department of Internal Medicine, 3Department of Laboratory Medicine, Saale-Unstrut Hospital Naumburg, Naumburg, GermanyBackground: The purpose of this observational study was to test the diagnostic performance of the Elecsys® troponin T high-sensitive system combined with copeptin measurement for early exclusion of acute myocardial infarction (MI in clinical practice.Methods: Troponin T high-sensitive (diagnostic cutoff: <14 pg/mL and copeptin (diagnostic cutoff: <14 pmol/L levels were determined at admission in addition to other routine laboratory parameters in patients with suspected acute MI presenting to the emergency department of a general hospital over a period of five months.Results: Data from 142 consecutive patients (mean age 71.2 ± 13.5 years, 76 men were analyzed. Final diagnoses were acute MI in 13 patients (nine ST elevation MI, four non-ST elevation MI, 9.2% unstable angina pectoris in three (2.1%, cardiac symptoms not primarily associated with myocardial ischemia in 79 (55.6%, and noncardiac disease in 47 patients (33.1%. The patients with acute MI were younger and had higher troponin T high-sensitive and copeptin values than patients without acute MI. Seventeen patients had very high copeptin values (>150 pmol/L, one of whom had a level of >700 pmol/L and died of pulmonary embolism. A troponin T high-sensitive level of <14 pg/mL in combination with copeptin <14 pmol/L at initial presentation ruled out acute MI in 45 of the 142 patients (31.7%, each with a sensitivity and negative predictive value of 100%.Conclusion: According to this early experience, a single determination of troponin T high-sensitive and copeptin may enable early and accurate exclusion of acute MI in one third of patients, even in an emergency department of a general hospital.Keywords: highly sensitive troponin T

  19. TLR 9 involvement in early protection induced by immunization with rPb27 against Paracoccidioidomycosis.

    Science.gov (United States)

    Morais, Elis Araujo; Chame, Daniela Ferreira; Melo, Eliza Mathias; de Carvalho Oliveira, Junnia Alvarenga; de Paula, Ana Cláudia Chagas; Peixoto, Andiara Cardoso; da Silva Santos, Lílian; Gomes, Dawidson Assis; Russo, Remo Castro; de Goes, Alfredo Miranda

    2016-02-01

    Paracoccidioidomycosis is caused by fungi of the Paracoccidioides genus and constitutes the most prevalent deep mycosis in Latin America. Toll-like receptors promote immune response against infectious agents. Recently, it was reported that TLR9 is crucial for mice survival during the first 48 h of P. brasiliensis infection. In this study, we used CPG oligodeoxynucleotide motif as an adjuvant with and without rPb27 to immunize mice against Paracoccidioidomycosis. CPG adjuvant induced differential recruitment of lymphocytes in the inflammatory process and a lower recruitment of neutrophils. In addition, CPG induced the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IL-6 and IL-12; increased phagocytic ability and microbicidal activity by macrophages; and induced differential production of lgG2a and lgG2b, subtypes of Ig. Knockout mice for TLR9 and IL-12 showed higher fungal loads and rates of mortality compared to control mice after 30 days of infection. The association between CPG and rPb27 induced a high level of protection against Paracoccidioidomycosis after the first 30 days of infection but not at 60 days. Our findings demonstrate that TLR 9 plays a role in the protection induced by immunization with rPb27 and confirms the importance of TLR9 in the initial protection against Paracoccidioidomycosis. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. Loss of Roquin induces early death and immune deregulation but not autoimmunity

    Science.gov (United States)

    Bertossi, Arianna; Aichinger, Martin; Sansonetti, Paola; Lech, Maciej; Neff, Frauke; Pal, Martin; Wunderlich, F. Thomas; Anders, Hans-Joachim; Klein, Ludger

    2011-01-01

    The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell–intrinsic and –extrinsic mechanisms, which itself was not sufficient to break self-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector–like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism. PMID:21844204

  1. Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.

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    Johan L M Björkegren

    2014-02-01

    Full Text Available Plasma cholesterol lowering (PCL slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80% and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-Apob (100/100 Mttp (flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions.

  2. The H-Impairment Index (HII): a standardized assessment of alcohol-induced impairment in the Emergency Department.

    Science.gov (United States)

    Hack, Jason B; Goldlust, Eric J; Gibbs, Frantz; Zink, Brian

    2014-03-01

    Emergency Departments (EDs) care for thousands of alcohol-intoxicated patients annually. No clinically relevant bedside measures currently exist to describe degree of impairment. To assess a group of bedside tests ("Hack's Impairment Index [HII] score") that applies a numerical value to the degree of alcohol-induced impairment in ED patients. A six-month retrospective review of HII score data was performed in a convenience sample of 293 intoxicated ED patients. Patients were scored 0-4 on five tasks, divided by the maximum score (20 if all tasks completed), every 2 hours; and classified by the number of visits: Low-frequency (1 visit); Medium-frequency (2 visits); High-frequency (≥3 visits). Correlations were assessed between HII score, healthcare provider judgment of intoxication, and measured alcohol levels. Study patients had 513 visits; 236 were low-frequency, 26 middle-frequency and 31 high-frequency. Clinical assessment and HII score were strongly correlated (Spearman's rho = 0.82, p < 0.001); clinical assessment and alcohol level less strongly so (rho = 0.49, p < 0.001). Among low-frequency patients, HII score and alcohol level were weakly correlated (r = 0.324, p < 0.001), with no such correlation among high-frequency visitors (r = -0.04, p = 0.89). The mean decline between serial HII scores was 0.126 (95% CI: 0.098-0.154). This pilot study shows the HII score can be performed at the bedside of alcohol-intoxicated patients. The HII declines in a reasonably predictable manner over time; and applies a quantitative, objective assessment of alcohol impairment.

  3. Early vessel destabilization mediated by Angiopoietin-2 and subsequent vessel maturation via Angiopoietin-1 induce functional neovasculature after ischemia.

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    Di Qin

    Full Text Available BACKGROUND: We assessed whether Angiopoietin-2 (Ang2, a Tie2 ligand and partial antagonist of Angiopoietin-1 (Ang1, is required for early vessel destabilization during postischemic angiogenesis, when combined with vascular growth factors. METHODS: In vitro, matrigel co-cultures assessed endothelial-cell tube formation and pericyte recruitment after stimulation of VEGF-A, Apelin (APLN, Ang1 with or without Ang2. In a murine hindlimb ischemia model, adeno-associated virus (rAAV, 3×10(12 virusparticles transduction of VEGF-A, APLN and Ang1 with or without Ang2 (continuous or early expression d0-3 was performed intramuscularly (d-14. Femoral artery ligation was performed at d0, followed by laser doppler perfusion meassurements (LDI 7 and 14. At d7 (early timepoint and d14 (late timepoint, histological analysis of capillary/muscle fiber ratio (CMF-R, PECAM-1 and pericyte/capillary ratio (PC-R, NG2 was performed. RESULTS: In vitro, VEGF-A, APLN and Ang1 induced ring formation, but only APLN and Ang1 recruited pericytes. Ang2 did not affect tube formation by APLN, but reduced pericyte recruitment after APLN or Ang1 overexpression. In vivo, rAAV.VEGF-A did not alter LDI-perfusion at d14, consistent with an impaired PC-R despite a rise in CMF-R. rAAV.APLN improved perfusion at d14, with or without continuous Ang2, increasing CMF-R and PC-R. rAAV.Ang1 improved perfusion at d14, when combined with rAAV.Ang2 (d0-3, accompanied by an increased CMF-R and PC-R. CONCLUSION: The combination of early vessel destabilization (Ang2 d0-3 and continuous Ang1 overexpression improves hindlimb perfusion, pointing to the importance of early vessel destabilization and subsequent vessel maturation for enhanced therapeutic neovascularization.

  4. Early anti-inflammatory intervention ameliorates axial disease in the proteoglycan-induced spondylitis mouse model of ankylosing spondylitis.

    Science.gov (United States)

    Tseng, Hsu-Wen; Glant, Tibor T; Brown, Matthew A; Kenna, Tony J; Thomas, Gethin P; Pettit, Allison R

    2017-05-30

    Ankylosing spondylitis (AS) is characterised by immune-mediated arthritis and osteoproliferation, ultimately leading to joint ankylosis. Whether inflammation is necessary for osteoproliferation is controversial, fuelled by the unclear efficacy of anti-inflammatory treatments on radiographic progression. In proteoglycan-induced spondylitis (PGISp), a mouse model of AS, inflammation is the prerequisite for osteoproliferation as osteoproliferation was only observed following inflammation-driven intervertebral disc (IVD) destruction. We hypothesised that early intervention with a potent anti-inflammatory therapy would protect IVD integrity and consequently alter disease progression. PGISp mice received vehicle or a combination of etanercept (ETN) plus prednisolone (PRD) therapy for 2 or 6 weeks initiated at an early disease stage. Peripheral arthritis was scored longitudinally. Spinal disease was assessed using a semi-quantitative histological scoring regimen including inflammation, joint destruction and excessive tissue formation. ETN + PRD therapy significantly delayed the onset of peripheral arthritis. IVD integrity was significantly protected when treatment was commenced in early disease. Six-weeks of treatment resulted in trends towards reductions in intervertebral joint damage and excessive tissue formation. IVD score distribution was dichotomized, likely reflecting the extent of axial disease at initiation of therapy. In the sub-group of mice with high IVD destruction scores, ETN + PRD treatment significantly reduced IVD destruction severity, inflammation and bone erosion and reduced cartilage damage and excessive tissue formation. Early intervention with anti-inflammatory treatment not only improved inflammatory symptoms but also ameliorated structural damage of spine in PGISp mice. This preclinical observation suggests that early anti-inflammatory intervention may slow radiographic progression in AS patients.

  5. Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat

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    S.S. Hu

    2014-03-01

    Full Text Available Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc and the early growth response gene-1 (Egr-1, appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC and auditory cortex (AC, in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

  6. High-frequency stimulation induces gradual immediate early gene expression in maturing adult-generated hippocampal granule cells.

    Science.gov (United States)

    Jungenitz, Tassilo; Radic, Tijana; Jedlicka, Peter; Schwarzacher, Stephan W

    2014-07-01

    Increasing evidence shows that adult neurogenesis of hippocampal granule cells is advantageous for learning and memory. We examined at which stage of structural maturation and age new granule cells can be activated by strong synaptic stimulation. High-frequency stimulation of the perforant pathway in urethane-anesthetized rats elicited expression of the immediate early genes c-fos, Arc, zif268 and pCREB133 in almost 100% of mature, calbindin-positive granule cells. In contrast, it failed to induce immediate early gene expression in immature doublecortin-positive granule cells. Furthermore, doublecortin-positive neurons did not react with c-fos or Arc expression to mild theta-burst stimulation or novel environment exposure. Endogenous expression of pCREB133 was increasingly present in young cells with more elaborated dendrites, revealing a close correlation to structural maturation. Labeling with bromodeoxyuridine revealed cell age dependence of stimulation-induced c-fos, Arc and zif268 expression, with only a few cells reacting at 21 days, but with up to 75% of cells activated at 35-77 days of cell age. Our results indicate an increasing synaptic integration of maturing granule cells, starting at 21 days of cell age, but suggest a lack of ability to respond to activation with synaptic potentiation on the transcriptional level as long as immature cells express doublecortin. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Two coffins and a funeral: early or late caspase activation determines two types of apoptosis induced by DNA damaging agents.

    Science.gov (United States)

    Oropesa-Ávila, Manuel; de la Cruz-Ojeda, Patricia; Porcuna, Jesús; Villanueva-Paz, Marina; Fernández-Vega, Alejandro; de la Mata, Mario; de Lavera, Isabel; Rivero, Juan Miguel Suarez; Luzón-Hidalgo, Raquel; Álvarez-Córdoba, Mónica; Cotán, David; Zaderenko, Ana Paula; Cordero, Mario D; Sánchez-Alcázar, José A

    2017-03-01

    Cell cytoskeleton makes profound changes during apoptosis including the organization of an Apoptotic Microtubule Network (AMN). AMN forms a cortical structure which plays an important role in preserving plasma membrane integrity during apoptosis. Here, we examined the cytoskeleton rearrangements during apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1α cells. Using fixed and living cell imaging, we showed that CPT induced two dose- and cell cycle-dependent types of apoptosis characterized by different cytoskeleton reorganizations, time-dependent caspase activation and final apoptotic cell morphology. In the one referred as "slow" (~h) or round-shaped, apoptosis was characterized by a slow contraction of the actinomyosin ring and late caspase activation. In "slow" apoptosis the γ-tubulin complexes were not disorganized and microtubules were not depolymerized at early stages. In contrast, "fast" (~min) or irregular-shaped apoptosis was characterized by early caspase activation followed by full contraction of the actinomyosin ring. In fast apoptosis γ-tubulin complexes were disorganized and microtubules were initially depolymerized. However, after actinomyosin contraction, microtubules were reformed adopting a cortical but irregular disposition near plasma membrane. In addition to distinctive cytoskeleton reorganization kinetics, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocytes response. Our results suggest that the knowledge and modulation of the type of apoptosis promoted by genotoxic agents may be important for deciding a better therapeutic option and predicting the immune response in cancer treatment.

  8. Early radiation-induced changes evaluated by intravoxel incoherent motion in the major salivary glands.

    Science.gov (United States)

    Marzi, Simona; Forina, Chiara; Marucci, Laura; Giovinazzo, Giuseppe; Giordano, Carolina; Piludu, Francesca; Landoni, Valeria; Spriano, Giuseppe; Vidiri, Antonello

    2015-04-01

    To investigate the potential of intravoxel incoherent motion (IVIM) MRI for early evaluation of irradiated major salivary glands. Thirty-four patients with head-neck cancer were included in a prospective study. All patients underwent three serial IVIM-MRI: before, half-way through, and at the end of radiotherapy (RT). Apparent diffusion coefficient (ADC), ADClow derived in the low b-value range, perfusion fraction f, and pure diffusion coefficient D were estimated. Pretreatment values and early changes of diffusion parameters were correlated with parotid mean dose (Dmean ) and volume reduction after RT. Changes in diffusion parameters over time were all significant (P salivary glands can be noninvasively evaluated by IVIM-MRI. Perfusion-related coefficients in conjunction with dosimetric information increase our capability to predict the change in parotid volume and hence, if further validated, guide treatment strategy in RT. © 2014 Wiley Periodicals, Inc.

  9. Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

    Science.gov (United States)

    Zhang, Jin-Bao; Chen, Ling; Lv, Zhu-Man; Niu, Xue-Yuan; Shao, Can-Can; Zhang, Chan; Pruski, Michal; Huang, Ying; Qi, Cong-Cong; Song, Ning-Ning; Lang, Bing; Ding, Yu-Qiang

    2016-12-13

    Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.

  10. Early diagnosis of melanotic melanoma based on laser-induced melanin fluorescence

    Science.gov (United States)

    Eichhorn, Reinhold; Wessler, Gerd; Scholz, Matthias; Leupold, Dieter; Stankovic, Goran; Buder, Susanne; Stücker, Markus; Hoffmann, Klaus

    2009-05-01

    Because of the increasing incidence of skin cancer, interest in using the autofluorescence of skin tissue as a noninvasive tool for early diagnosis is enforced. Focus is especially on malignant melanotic melanoma. On the basis of a newly developed method to selectively excite melanin fluorescence of skin tissue by stepwise two-photon excitation with nanosecond laser pulses at 810 nm, we have investigated information from this melanin fluorescence with respect to the differentiation of pigmented lesions. A distinct difference in the melanin fluorescence spectrum of malignant melanoma (including melanoma in situ) when compared to that of benign melanocytic lesions (i.e., common nevi) has been found for freshly excised samples as well as for histopathological samples. There is also specific fluorescence from dysplastic nevi. In this way, early detection of malignant melanoma is possible.

  11. The origin of early age expansions induced in cementitious materials containing shrinkage reducing admixtures

    International Nuclear Information System (INIS)

    Sant, Gaurav; Lothenbach, Barbara; Juilland, Patrick; Le Saout, Gwenn; Weiss, Jason; Scrivener, Karen

    2011-01-01

    Studies on the early-age shrinkage behavior of cement pastes, mortars, and concretes containing shrinkage reducing admixtures (SRAs) have indicated these mixtures frequently exhibit an expansion shortly after setting. While the magnitude of the expansion has been noted to be a function of the chemistry of the cement and the admixture dosage; the cause of the expansion is not clearly understood. This investigation uses measurements of autogenous deformation, X-ray diffraction, pore solution analysis, thermogravimetry, and scanning electron microscopy to study the early-age properties and describe the mechanism of the expansion in OPC pastes made with and without SRA. The composition of the pore solution indicates that the presence of the SRA increases the portlandite oversaturation level in solution which can result in higher crystallization stresses which could lead to an expansion. This observation is supported by deformation calculations for the systems examined.

  12. Evaluating the forced oscillation technique in the detection of early smoking-induced respiratory changes

    OpenAIRE

    Faria, Alvaro CD; Lopes, Agnaldo J; Jansen, Jos? M; Melo, Pedro L

    2009-01-01

    Abstract Background Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD). The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system. The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD i...

  13. Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood

    Directory of Open Access Journals (Sweden)

    Kely ede Picoli Souza

    2015-04-01

    Full Text Available We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system is expressed and functional in the white adipose tissue (WAT and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass or saline, starting at the first day of life until the age of 16 days. Between days 90th and 180th, a group of these animals received high fat diet (HFD. Molecular, biochemical, histological and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY and cocaine- and amphetamine-regulated transcript (CART gene expression in hypothalamus, fatty acid synthase (FAS and hormone-sensitive lipase (HSL gene expression in retroperitoneal WAT and decreases peroxixome proliferators-activated receptor (PPAR γ, PPARα, uncoupling protein (UCP 2 and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood.

  14. Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat

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    Cristina A Ghiani

    2011-10-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  15. Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children

    Directory of Open Access Journals (Sweden)

    Sarah E. Cusick

    2018-02-01

    Full Text Available Iron deficiency is the most common micronutrient deficiency in the world. Women of reproductive age and young children are particularly vulnerable. Iron deficiency in late prenatal and early postnatal periods can lead to long-term neurobehavioral deficits, despite iron treatment. This may occur because screening and treatment of iron deficiency in children is currently focused on detection of anemia and not neurodevelopment. Anemia is the end-stage state of iron deficiency. The brain becomes iron deficient before the onset of anemia due to prioritization of the available iron to the red blood cells (RBCs over other organs. Brain iron deficiency, independent of anemia, is responsible for the adverse neurological effects. Early diagnosis and treatment of impending brain dysfunction in the pre-anemic stage is necessary to prevent neurological deficits. The currently available hematological indices are not sensitive biomarkers of brain iron deficiency and dysfunction. Studies in non-human primate models suggest that serum proteomic and metabolomic analyses may be superior for this purpose. Maternal iron supplementation, delayed clamping or milking of the umbilical cord, and early iron supplementation improve the iron status of at-risk infants. Whether these strategies prevent iron deficiency-induced brain dysfunction has yet to be determined. The potential for oxidant stress, altered gastrointestinal microbiome and other adverse effects associated with iron supplementation cautions against indiscriminate iron supplementation of children in malaria-endemic regions and iron-sufficient populations.

  16. Application of Laser Induced Breakdown Spectroscopy in Early Detection of Red Palm Weevil: (Rhynchophorus ferrugineus) Infestation in Date Palm

    Science.gov (United States)

    A. Farooq, W.; G. Rasool, K.; Walid, Tawfik; S. Aldawood, A.

    2015-11-01

    The Kingdom of Saudi Arabia is one of the leading date producing countries. Unfortunately, this important fruit crop is under great threat from the red palm weevil (RPW) (Rhynchophorus ferrugineus), which is a highly invasive pest. Several techniques, including visual inspection, acoustic sensors, sniffer dogs, and pheromone traps have been tried to detect the early stages of a RPW infestation; however, each method has suffered certain logistical and implementation issues. We have applied laser induced breakdown spectroscopy (LIBS) for the early detection of RPW infestation. Through the analysis of the observed LIBS spectra of different infested and healthy samples, we have found presence of Ca, Mg, Na, C, K elements and OH, CN molecules. The spectra also reveal that with the population growth of the pest, the intensity of Mg and Ca atomic lines in LIBS spectra increases rapidly. Similar behavior is observed in the molecular lines of LIBS spectra. The obtained results indicate that the LIBS technique can be used for the early detection of RPW infestation without damaging the date palms.

  17. Hypoxia-inducible factor-1α activation improves renal oxygenation and mitochondrial function in early chronic kidney disease.

    Science.gov (United States)

    Thomas, Joanna L; Pham, Hai; Li, Ying; Hall, Elanore; Perkins, Guy A; Ali, Sameh S; Patel, Hemal H; Singh, Prabhleen

    2017-08-01

    The pathophysiology of chronic kidney disease (CKD) is driven by alterations in surviving nephrons to sustain renal function with ongoing nephron loss. Oxygen supply-demand mismatch, due to hemodynamic adaptations, with resultant hypoxia, plays an important role in the pathophysiology in early CKD. We sought to investigate the underlying mechanisms of this mismatch. We utilized the subtotal nephrectomy (STN) model of CKD to investigate the alterations in renal oxygenation linked to sodium (Na) transport and mitochondrial function in the surviving nephrons. Oxygen delivery was significantly reduced in STN kidneys because of lower renal blood flow. Fractional oxygen extraction was significantly higher in STN. Tubular Na reabsorption was significantly lower per mole of oxygen consumed in STN. We hypothesized that decreased mitochondrial bioenergetic capacity may account for this and uncovered significant mitochondrial dysfunction in the early STN kidney: higher oxidative metabolism without an attendant increase in ATP levels, elevated superoxide levels, and alterations in mitochondrial morphology. We further investigated the effect of activation of hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular hypoxia response. We observed significant improvement in renal blood flow, glomerular filtration rate, and tubular Na reabsorption per mole of oxygen consumed with HIF-1α activation. Importantly, HIF-1α activation significantly lowered mitochondrial oxygen consumption and superoxide production and increased mitochondrial volume density. In conclusion, we report significant impairment of renal oxygenation and mitochondrial function at the early stages of CKD and demonstrate the beneficial role of HIF-1α activation on renal function and metabolism.

  18. pH regulation in early endosomes and interferon-inducible transmembrane proteins control avian retrovirus fusion.

    Science.gov (United States)

    Desai, Tanay M; Marin, Mariana; Mason, Caleb; Melikyan, Gregory B

    2017-05-12

    Enveloped viruses infect host cells by fusing their membranes with those of the host cell, a process mediated by viral glycoproteins upon binding to cognate host receptors or entering into acidic intracellular compartments. Whereas the effect of receptor density on viral infection has been well studied, the role of cell type-specific factors/processes, such as pH regulation, has not been characterized in sufficient detail. Here, we examined the effects of cell-extrinsic factors (buffer environment) and cell-intrinsic factors (interferon-inducible transmembrane proteins, IFITMs), on the pH regulation in early endosomes and on the efficiency of acid-dependent fusion of the avian sarcoma and leukosis virus (ASLV), with endosomes. First, we found that a modest elevation of external pH can raise the pH in early endosomes in a cell type-dependent manner and thereby delay the acid-induced fusion of endocytosed ASLV. Second, we observed a cell type-dependent delay between the low pH-dependent and temperature-dependent steps of viral fusion, consistent with the delayed enlargement of the fusion pore. Third, ectopic expression of IFITMs, known to potently block influenza virus fusion with late compartments, was found to only partially inhibit ASLV fusion with early endosomes. Interestingly, IFITM expression promoted virus uptake and the acidification of endosomal compartments, resulting in an accelerated fusion rate when driven by the glycosylphosphatidylinositol-anchored, but not by the transmembrane isoform of the ASLV receptor. Collectively, these results highlight the role of cell-extrinsic and cell-intrinsic factors in regulating the efficiency and kinetics of virus entry and fusion with target cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Anorectal emergencies

    Science.gov (United States)

    Lohsiriwat, Varut

    2016-01-01

    Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up. PMID:27468181

  20. Radiation and chemotherapy bystander effects induce early genomic instability events: Telomere shortening and bridge formation coupled with mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gorman, Sheeona; Tosetto, Miriam [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); Lyng, Fiona; Howe, Orla [Radiation and Environmental Science Centre, Dublin Institute of Technology and St. Luke' s Hospital, Dublin (Ireland); Sheahan, Kieran; O' Donoghue, Diarmuid; Hyland, John; Mulcahy, Hugh [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); O' Sullivan, Jacintha, E-mail: jacintha.osullivan@ucd.ie [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland)

    2009-10-02

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2 Gy, 5 Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0 Gy) at 24 h. There was no significant difference between 2 Gy and 5 Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2 Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p = 0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p = 0.02) and mitochondrial membrane potential increased (p = 0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring

  1. Early Zn2+-induced effects on membrane potential account for primary heavy metal susceptibility in tolerant and sensitive Arabidopsis species

    Science.gov (United States)

    Kenderešová, Lucia; Staňová, Andrea; Pavlovkin, Ján; Ďurišová, Eva; Nadubinská, Miriam; Čiamporová, Milada; Ovečka, Miroslav

    2012-01-01

    Background and Aims Uptake of heavy metals by plant root cells depends on electro-physiological parameters of the plasma membrane. In this study, responses of the plasma membrane in root cells were analysed where early reactions to the metal ion-induced stress are localized. Three different Arabidopsis species with diverse strategies of their adaptation to heavy metals were compared: sensitive Arabidopsis thaliana and tolerant A. halleri and A. arenosa. Methods Plants of A. thaliana Col-0 ecotype and plants of A. arenosa and A. halleri originating from natural metallicolous populations were exposed to high concentrations of Zn2+. Plants were tested for root growth rate, cellular tolerance, plant morphology and cell death in the root apex. In addition, the membrane potential (EM) of mature cortical root cells and changes in the pH of the liquid culture media were measured. Key Results Primary roots of A. halleri and A. arenosa plants grew significantly better at increased Zn2+ concentrations than A. thaliana plants. Elevated Zn2+ concentrations in the culture medium induced rapid changes in EM. The reaction was species-specific and concentration-dependent. Arabidopsis halleri revealed the highest insensitivity of the plasma membrane and the highest survival rate under prolonged treatment with extra-high concentrations. Plants were able to effectively adjust the pH in the control, but much less at Zn2+-induced lower pH. Conclusions The results indicate a similar mode of early reaction to Zn2+, but with different extent in tolerant and sensitive species of Arabidopsis. The sensitivity of A. thaliana and a high tolerance of A. halleri and A. arenosa were demonstrated. Plasma membrane depolarization was lowest in the hyperaccumulator A. halleri and highest in A. thaliana. This indicates that rapid membrane voltage changes are an excellent tool to monitor the effects of heavy metals. PMID:22645116

  2. Radiation and chemotherapy bystander effects induce early genomic instability events: telomere shortening and bridge formation coupled with mitochondrial dysfunction.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2Gy, 5Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0Gy) at 24h. There was no significant difference between 2Gy and 5Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p=0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p=0.02) and mitochondrial membrane potential increased (p=0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring mitochondrial

  3. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation

    DEFF Research Database (Denmark)

    Barbatelli, G.; Murano, I.; Madsen, Lise

    2010-01-01

    The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT after cold acclimatization have a mixed morphology (paucilocular adipocytes). These cells also had...... for C/EBP (an antimitotic protein), whereas Ccna1 expression (related to cell proliferation) was unchanged. Overall, our data strongly suggest that the cold-induced emergence of brown adipocytes in WAT predominantly reflects ß3-adrenoceptor-mediated transdifferentiation....

  4. Early events induced by the toxin deoxynivalenol lead to programmed cell death in Nicotiana tabacum cells.

    Science.gov (United States)

    Yekkour, Amine; Tran, Daniel; Arbelet-Bonnin, Delphine; Briand, Joël; Mathieu, Florence; Lebrihi, Ahmed; Errakhi, Rafik; Sabaou, Nasserdine; Bouteau, François

    2015-09-01

    Deoxynivalenol (DON) is a mycotoxin affecting animals and plants. This toxin synthesized by Fusarium culmorum and Fusarium graminearum is currently believed to play a decisive role in the fungal phytopathogenesis as a virulence factor. Using cultured cells of Nicotiana tabacum BY2, we showed that DON-induced programmed cell death (PCD) could require transcription and translation processes, in contrast to what was observed in animal cells. DON could induce different cross-linked pathways involving (i) reactive oxygen species (ROS) generation linked, at least partly, to a mitochondrial dysfunction and a transcriptional down-regulation of the alternative oxidase (Aox1) gene and (ii) regulation of ion channel activities participating in cell shrinkage, to achieve PCD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Raquel R Bartz

    Full Text Available Acute kidney injury (AKI contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control, 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection.

  6. External gamma irradiation-induced effects in early-life stages of zebrafish, Danio rerio

    International Nuclear Information System (INIS)

    Gagnaire, B.; Cavalié, I.; Pereira, S.; Floriani, M.; Dubourg, N.; Camilleri, V.; Adam-Guillermin, C.

    2015-01-01

    Highlights: • The present study aimed to evaluate the effects of gamma rays on zebrafish larvae. • Different techniques were used: gene expression, biochemistry, microscopy and macroscopical observations. • The results showed that gamma irradiation can alter embryo-larval development at several levels of organization. - Abstract: In the general context of validation of tools useful for the characterization of ecological risk linked to ionizing radiation, the effects of an external gamma irradiation were studied in zebrafish larvae irradiated for 96 h with two dose rates: 0.8 mGy/d, which is close to the level recommended to protect ecosystems from adverse effects of ionizing radiation (0.24 mGy/d) and a higher dose rate of 570 mGy/d. Several endpoints were investigated, such as mortality, hatching, and some parameters of embryo-larval development, immunotoxicity, apoptosis, genotoxicity, neurotoxicity and histological alterations. Results showed that an exposure to gamma rays induced an acceleration of hatching for both doses and a decrease of yolk bag diameter for the highest dose, which could indicate an increase of global metabolism. AChE activity decreased with the low dose rate of gamma irradiation and alterations were also shown in muscles of irradiated larvae. These results suggest that gamma irradiation can induce damages on larval neurotransmission, which could have repercussions on locomotion. DNA damages, basal ROS production and apoptosis were also induced by irradiation, while ROS stimulation index and EROD biotransformation activity were decreased and gene expression of acetylcholinesterase, choline acetyltransferase, cytochrome p450 and myeloperoxidase increased. These results showed that ionizing radiation induced an oxidative stress conducting to DNA damages. This study characterized further the modes of action of ionizing radiation in fish.

  7. External gamma irradiation-induced effects in early-life stages of zebrafish, Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Gagnaire, B., E-mail: beatrice.gagnaire@irsn.fr [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France); Cavalié, I. [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France); Pereira, S. [Neolys Diagnostics, Lyon 69373 (France); Floriani, M.; Dubourg, N.; Camilleri, V.; Adam-Guillermin, C. [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France)

    2015-12-15

    Highlights: • The present study aimed to evaluate the effects of gamma rays on zebrafish larvae. • Different techniques were used: gene expression, biochemistry, microscopy and macroscopical observations. • The results showed that gamma irradiation can alter embryo-larval development at several levels of organization. - Abstract: In the general context of validation of tools useful for the characterization of ecological risk linked to ionizing radiation, the effects of an external gamma irradiation were studied in zebrafish larvae irradiated for 96 h with two dose rates: 0.8 mGy/d, which is close to the level recommended to protect ecosystems from adverse effects of ionizing radiation (0.24 mGy/d) and a higher dose rate of 570 mGy/d. Several endpoints were investigated, such as mortality, hatching, and some parameters of embryo-larval development, immunotoxicity, apoptosis, genotoxicity, neurotoxicity and histological alterations. Results showed that an exposure to gamma rays induced an acceleration of hatching for both doses and a decrease of yolk bag diameter for the highest dose, which could indicate an increase of global metabolism. AChE activity decreased with the low dose rate of gamma irradiation and alterations were also shown in muscles of irradiated larvae. These results suggest that gamma irradiation can induce damages on larval neurotransmission, which could have repercussions on locomotion. DNA damages, basal ROS production and apoptosis were also induced by irradiation, while ROS stimulation index and EROD biotransformation activity were decreased and gene expression of acetylcholinesterase, choline acetyltransferase, cytochrome p450 and myeloperoxidase increased. These results showed that ionizing radiation induced an oxidative stress conducting to DNA damages. This study characterized further the modes of action of ionizing radiation in fish.

  8. Cross-fostering reduces obesity induced by early exposure to monosodium glutamate in male rats.

    Science.gov (United States)

    Miranda, Rosiane Aparecida; da Silva Franco, Claudinéia Conationi; de Oliveira, Júlio Cezar; Barella, Luiz Felipe; Tófolo, Laize Peron; Ribeiro, Tatiane Aparecida; Pavanello, Audrei; da Conceição, Ellen Paula Santos; Torrezan, Rosana; Armitage, James; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar; de Freitas Mathias, Paulo Cezar; Vieira, Elaine

    2017-01-01

    Maternal obesity programmes a range of metabolic disturbances for the offspring later in life. Moreover, environmental changes during the suckling period can influence offspring development. Because both periods significantly affect long-term metabolism, we aimed to study whether cross-fostering during the lactation period was sufficient to rescue a programmed obese phenotype in offspring induced by maternal obesity following monosodium L-glutamate (MSG) treatment. Obesity was induced in female Wistar rats by administering subcutaneous MSG (4 mg/g body weight) for the first 5 days of postnatal life. Control and obese female rats were mated in adulthood. The resultant pups were divided into control second generation (F 2 ) (CTLF 2 ), MSG-treated second generation (F 2 ) (MSGF 2 ), which suckled from their CTL and MSG biological dams, respectively, or CTLF 2 -CR, control offspring suckled by MSG dams and MSGF 2 -CR, MSG offspring suckled by CTL dams. At 120 days of age, fat tissue accumulation, lipid profile, hypothalamic leptin signalling, glucose tolerance, glucose-induced, and adrenergic inhibition of insulin secretion in isolated pancreatic islets were analysed. Maternal MSG-induced obesity led to an obese phenotype in male offspring, characterized by hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, dyslipidaemia, and impaired leptin signalling, suggesting central leptin resistance, glucose intolerance, impaired glucose-stimulated, and adrenergic inhibition of insulin secretion. Cross-fostering normalized body weight, food intake, leptin signalling, lipid profiles, and insulinaemia, but not glucose homeostasis or insulin secretion from isolated pancreatic islets. Our findings suggest that alterations during the lactation period can mitigate the development of obesity and prevent the programming of adult diseases.

  9. Mechanism study of laser cochleostomy-induced early hearing loss in a rat model.

    Science.gov (United States)

    Ye, Qing; Geng, Yang; Zhang, Xian-Zeng; Chen, Wen-Lie; Tian, Tian-Jie; Xie, Shu-Sen; Huang, Zheng

    2014-03-01

    Hearing loss following laser-assisted ear surgery has been reported. However, the mechanism responsible for the hearing loss remains largely speculative. The aim of this study was to investigate the correlation between laser-induced hearing loss and changes in the number of hair cell ribbon synapses and ultrastructure in the cochlea. Laser cochleostomy was performed with a superpulsed carbon dioxide (CO2) laser at 2 and 5 W in Sprague-Dawley rats. Auditory brainstem responses (ABRs) were measured preoperatively and 2 days after surgery. The synapse numbers in apical and middle cochlear turns were quantified. Transmission electron microscopy was employed to further examine the subcellular changes in the cochlea. Click and tonal ABR threshold shifts in both 2 and 5-W groups displayed a frequency-dependent loss within the frequency range measured. Laser cochleostomy induced a significant decrease of synapse numbers in the middle turn in both groups (p laser-caused hearing loss even under low-energy laser cochleostomy. The high-energy laser-induced hearing loss was associated with more reduction of synapse number.

  10. Early emergence of entecavir-resistant hepatitis B virus in a patient with hepatitis B virus/human immunodeficiency virus coinfection.

    Science.gov (United States)

    Kanada, Aimi; Takehara, Tetsuo; Ohkawa, Kazuyoshi; Kato, Michio; Tatsumi, Tomohide; Miyagi, Takuya; Sakamori, Ryotaro; Yamaguchi, Shinjiro; Uemura, Akio; Kohga, Keisuke; Sasakawa, Akira; Hikita, Hayato; Kawamura, Kiyomi; Kanto, Tatsuya; Hiramatsu, Naoki; Hayashi, Norio

    2008-06-01

    The efficacy of entecavir for patients with hepatitis B virus/human immunodeficiency virus coinfection has not been fully elucidated. Here we examined a patient coinfected with both viruses in whom entecavir-resistant hepatitis B virus appeared. The 60-year-old Japanese male with the coinfection received antiretroviral therapy including lamivudine. The therapy initially suppressed replication of both viruses, followed by reactivation of the hepatitis B virus alone by 2 years of therapy. He subsequently received entecavir therapy in addition to the antiretroviral regimen. After entecavir administration, the hepatitis B virus DNA level was slightly reduced, but then increased after 6 months of entecavir therapy. In the sequencing analysis of hepatitis B virus, no drug resistance-associated amino acid substitutions were observed in the reverse transcriptase (rt) domain before antiretroviral therapy. The lamivudine-resistant amino acid substitutions at rt173, rt180 and rt204 were detected before entecavir administration, and further the entecavir-resistant rt202 substitution was observed after 6 months of entecavir therapy. The full-length hepatitis B sequences showed that the viral strain derived from the patient belonged to genotype H. In summary, this report describes a patient with hepatitis B virus/human immunodeficiency virus coinfection who received entecavir therapy in addition to an antiretroviral regimen and showed the early emergence of entecavir-resistance hepatitis B virus. In entecavir therapy for patients infected with both viruses, great care should be taken with respect to the emergence of entecavir-resistant hepatitis B virus, especially in patients with pre-existing lamivudine-resistant virus.

  11. Efficacy and acceptability of a mifepristone-misoprostol combined regimen for early induced abortion among women in Mexico City.

    Science.gov (United States)

    Peña, Melanie; Dzuba, Ilana G; Smith, Patricio Sanhueza; Mendoza, Luis Jorge Arellano; Bousiéguez, Manuel; Martínez, María Laura García; Polanco, Ranulfo Ríos; Villalón, Antonio Eduardo Flores; Winikoff, Beverly

    2014-10-01

    To evaluate the experience of women receiving mifepristone-misoprostol for early induced abortion in public sector facilities in the Federal District of Mexico City. An open-label prospective study was conducted with 1000 pregnant women who sought induced abortion with a pregnancy of up to 63days of gestation, as measured from the date of their last menstrual period. The study was conducted in three public sector healthcare facilities: two secondary level hospitals and one primary care clinic. Women ingested 200mg mifepristone on day 1, followed by 800μg buccal misoprostol 24hours later, and they returned for follow-up on day 8. The primary outcome was complete abortion without recourse to surgical intervention. A total of 971 women received mifepristone-misoprostol and were included in the analysis for efficacy of treatment. The overall efficacy of the combined medical abortion regimen studied was 97.3% (n=945); the success rate did not vary significantly by gestational age (95.9%-100%; P=0.449). Most women (n=922, 95.0%) had a successful induced abortion with only one dose of misoprostol. The combined mifepristone and buccal misoprostol regimen was found to be highly effective and acceptable among Mexican women. www.ClinicalTrials.gov: NCT00386282. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Ethosuximide-induced Stevens-Johnson syndrome: Beneficial effect of early intervention with high-dose corticosteroid therapy.

    Science.gov (United States)

    Tachibana, Kota; Hamada, Toshihisa; Tsuchiya, Hiroki; Shibata, Takashi; Fujii, Kazuyasu; Kobayashi, Katsuhiro; Iwatsuki, Keiji

    2018-02-11

    We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens-Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients. © 2018 Japanese Dermatological Association.

  13. Amphetamine and Dopamine-Induced Immediate Early Gene Expression in Striatal Neurons Depends on Postsynaptic NMDA Receptors and Calcium

    Science.gov (United States)

    Konradi, Christine; Leveque, Jean-Christophe; Hyman, Steven E.

    2014-01-01

    Amphetamine and cocaine induce the expression of both immediate early genes (IEGs) and neuropeptide genes in rat striatum. Despite the demonstrated dependence of these effects on D1 dopamine receptors, which activate the cyclic AMP pathway, there are several reports that amphetamine and cocaine-induced IEG expression can be inhibited in striatum in vivo by NMDA receptor antagonists. We find that in vivo, the NMDA receptor antagonist MK-801 inhibits amphetamine induction of c-fos acutely and also prevents downregulation of IEG expression with chronic amphetamine administration. Such observations raise the question of whether dopamine/glutamate interactions occur at the level of corticostriatal and mesostriatal circuitry or within striatal neurons. Therefore, we studied dissociated striatal cultures in which midbrain and cortical presynaptic inputs are removed. In these cultures, we find that dopamine- or forskolin-mediated IEG induction requires Ca2+ entry via NMDA receptors but not via L-type Ca2+ channels. Moreover, blockade of NMDA receptors diminishes the ability of dopamine to induce phosphorylation of the cyclic AMP responsive element binding protein CREB. Although these results do not rule out a role for circuit-level dopamine/glutamate interactions, they demonstrate a requirement at the cellular level for interactions between the cyclic AMP and NMDA receptor pathways in dopamine-regulated gene expression in striatal neurons. PMID:8753884

  14. DELLA-induced early transcriptional changes during etiolated development in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Javier Gallego-Bartolomé

    Full Text Available The hormones gibberellins (GAs control a wide variety of processes in plants, including stress and developmental responses. This task largely relies on the activity of the DELLA proteins, nuclear-localized transcriptional regulators that do not seem to have DNA binding capacity. The identification of early target genes of DELLA action is key not only to understand how GAs regulate physiological responses, but also to get clues about the molecular mechanisms by which DELLAs regulate gene expression. Here, we have investigated the global, early transcriptional response triggered by the Arabidopsis DELLA protein GAI during skotomorphogenesis, a developmental program tightly regulated by GAs. Our results show that the induction of GAI activity has an almost immediate effect on gene expression. Although this transcriptional regulation is largely mediated by the PIFs and HY5 transcription factors based on target meta-analysis, additional evidence points to other transcription factors that would be directly involved in DELLA regulation of gene expression. First, we have identified cis elements recognized by Dofs and type-B ARRs among the sequences enriched in the promoters of GAI targets; and second, an enrichment in additional cis elements appeared when this analysis was extended to a dataset of early targets of the DELLA protein RGA: CArG boxes, bound by MADS-box proteins, and the E-box CACATG that links the activity of DELLAs to circadian transcriptional regulation. Finally, Gene Ontology analysis highlights the impact of DELLA regulation upon the homeostasis of the GA, auxin, and ethylene pathways, as well as upon pre-existing transcriptional networks.

  15. Computational chemistry approach for the early detection of drug-induced idiosyncratic liver toxicity.

    Science.gov (United States)

    Cruz-Monteagudo, Maykel; Cordeiro, M Natália D S; Borges, Fernanda

    2008-03-01

    Idiosyncratic drug toxicity (IDT), considered as a toxic host-dependent event, with an apparent lack of dose response relationship, is usually not predictable from early phases of clinical trials, representing a particularly confounding complication in drug development. Albeit a rare event (usually approach proposed in the present study, can play an important role in addressing IDT in early drug discovery. We report for the first time a systematic evaluation of classification models to predict idiosyncratic hepatotoxicity based on linear discriminant analysis (LDA), artificial neural networks (ANN), and machine learning algorithms (OneR) in conjunction with a 3D molecular structure representation and feature selection methods. These modeling techniques (LDA, feature selection to prevent over-fitting and multicollinearity, ANN to capture nonlinear relationships in the data, as well as the simple OneR classifier) were found to produce QSTR models with satisfactory internal cross-validation statistics and predictivity on an external subset of chemicals. More specifically, the models reached values of accuracy/sensitivity/specificity over 84%/78%/90%, respectively in the training series along with predictivity values ranging from ca. 78 to 86% of correctly classified drugs. An LDA-based desirability analysis was carried out in order to select the levels of the predictor variables needed to trigger the more desirable drug, i.e. the drug with lower potential for idiosyncratic hepatotoxicity. Finally, two external test sets were used to evaluate the ability of the models in discriminating toxic from nontoxic structurally and pharmacologically related drugs and the ability of the best model (LDA) in detecting potential idiosyncratic hepatotoxic drugs, respectively. The computational approach proposed here can be considered as a useful tool in early IDT prognosis.

  16. THE EMERGENCE OF EARLY KINDOMS IN SOUTH SULAWESI: A Preliminary Remark on Governmental Contracts from the Thirteenth to the Fifteenth Century

    Directory of Open Access Journals (Sweden)

    Andi` Zainal Abidin

    2014-07-01

    Full Text Available Pactum subjectionis or governmental contract is a covenant or compact between the ruler and the ruled envisaging their mutual rights and responsibilities [Abidin 1971:159; Harvey 1974:18; Riekerk quoting Catlin 1969:12]. Among the early states discussed by various scholars, e.g., Claesen and Skalnik (1978, Geertz (1979, Selo Soemardjan (1978, Coedes (1967, Hall and Whitmore (Aeusrivongse 1979, Reid and Castles (Macknight 1975, none subscribed to the practice of governmental contracts, except Bone in South Sulawesi. Despite its uniqueness, to my knowledge nothing has been written on the pactum subjectionis of early kingdoms on South Sulawesi, nor has any research been undertaken on this subject. This paper discusses the formation of main kingdoms in South Sulawesi and especially the governmental contract in the so-called Cappagalae (he big three–Luwu’, Bone and Gowa; two members of Tellumpoccoe (the three allied kingdoms in 1592, that is, Wajo’ and Soppeng; and a petty kingdom already known in the I La Galigo Epic Cycle, Cina, later called Pammana. Examples of such govermental contract are found at the beginning sections of historical chronicles (Lontara’ attoriolong. Usually the very first parts of the chronicles contain a political myth which explains the origin of a dynasty as founded by a king or queen descending from heaven. Thus prior to the emergence of kingdoms in South Sulawesi, the first king called To Manurung (lit. He who came from the sky had to make a contract with the representatives of the people called Ulu Anang or Matoa (BugisorKasuwiang(Makassar.

  17. Psychological and psychobiological responses to immediate early intervention in the emergency department: Case report of one-session exposure therapy for the prevention of PTSD.

    Science.gov (United States)

    Post, Loren M; Michopoulos, Vasiliki; Stevens, Jennifer S; Reddy, Renuka; Maples, Jessica L; Morgan, Jessica R; Rothbaum, Alex O; Jovanovic, Tanja; Ressler, Kerry J; Rothbaum, Barbara O

    2017-01-01

    Research suggests that exposure therapy provided in the hours immediately following trauma exposure may prevent PTSD development. This case report presents data on an at-risk for PTSD participant involved in a motor-vehicle crash that caused her severe distress. She received one session of exposure therapy in the emergency department (ED) as part of an ongoing randomized controlled study examining the optimal dose of exposure therapy in the immediate aftermath of trauma. PTSD and depression measures were collected at pre-treatment assessment and one- and three-month follow-up. Potential PTSD biomarkers were also examined. Psychophysiological reactions were measured using skin conductance data measured on an iPad during the exposure therapy session and the follow-up assessments. A fear-potentiated startle paradigm and an functional magnetic resonance imaging (fMRI) behavioral inhibition task were used at follow-up. The participant demonstrated subjective and psychophysiological extinction from pre- to post-imaginal exposure. At follow-up, she did not meet DSM-IV criteria for PTSD or demonstrate hyperarousal to trauma reminders and showed robust fear extinction and the ability to inhibit responses in an fMRI behavioral inhibition task. In line with previous early intervention for the prevention of PTSD studies, this case report supports the need for ongoing empirical research investigating the possibility that one session of exposure therapy in the ED may attenuate risk for PTSD. Furthermore, the current findings demonstrate psychophysiological extinction serving as a prognostic indicator of treatment response for PTSD early intervention to be an exciting avenue to explore in future systematic research.

  18. Psychological and psychobiological responses to immediate early intervention in the emergency department: Case report of one-session exposure therapy for the prevention of PTSD

    Science.gov (United States)

    Post, Loren M.; Michopoulos, Vasiliki; Stevens, Jennifer S.; Reddy, Renuka; Maples, Jessica L.; Morgan, Jessica R.; Rothbaum, Alex O.; Jovanovic, Tanja; Ressler, Kerry J.; Rothbaum, Barbara O.

    2017-01-01

    Research suggests that exposure therapy provided in the hours immediately following trauma exposure may prevent PTSD development. This case report presents data on an at-risk for PTSD participant involved in a motor-vehicle crash that caused her severe distress. She received one session of exposure therapy in the emergency department (ED) as part of an ongoing randomized controlled study examining the optimal dose of exposure therapy in the immediate aftermath of trauma. PTSD and depression measures were collected at pre-treatment assessment and one- and three-month follow-up. Potential PTSD biomarkers were also examined. Psychophysiological reactions were measured using skin conductance data measured on an iPad during the exposure therapy session and the follow-up assessments. A fear-potentiated startle paradigm and an functional magnetic resonance imaging (fMRI) behavioral inhibition task were used at follow-up. The participant demonstrated subjective and psychophysiological extinction from pre- to post-imaginal exposure. At follow-up, she did not meet DSM-IV criteria for PTSD or demonstrate hyperarousal to trauma reminders and showed robust fear extinction and the ability to inhibit responses in an fMRI behavioral inhibition task. In line with previous early intervention for the prevention of PTSD studies, this case report supports the need for ongoing empirical research investigating the possibility that one session of exposure therapy in the ED may attenuate risk for PTSD. Furthermore, the current findings demonstrate psychophysiological extinction serving as a prognostic indicator of treatment response for PTSD early intervention to be an exciting avenue to explore in future systematic research. PMID:28993816

  19. Early spring, severe frost events, and drought induce rapid carbon loss in high elevation meadows.

    Directory of Open Access Journals (Sweden)

    Chelsea Arnold

    Full Text Available By the end of the 20th century, the onset of spring in the Sierra Nevada mountain range of California has been occurring on average three weeks earlier than historic records. Superimposed on this trend is an increase in the presence of highly anomalous "extreme" years, where spring arrives either significantly late or early. The timing of the onset of continuous snowpack coupled to the date at which the snowmelt season is initiated play an important role in the development and sustainability of mountain ecosystems. In this study, we assess the impact of extreme winter precipitation variation on aboveground net primary productivity and soil respiration over three years (2011 to 2013. We found that the duration of snow cover, particularly the timing of the onset of a continuous snowpack and presence of early spring frost events contributed to a dramatic change in ecosystem processes. We found an average 100% increase in soil respiration in 2012 and 2103, compared to 2011, and an average 39% decline in aboveground net primary productivity observed over the same time period. The overall growing season length increased by 57 days in 2012 and 61 days in 2013. These results demonstrate the dependency of these keystone ecosystems on a stable climate and indicate that even small changes in climate can potentially alter their resiliency.

  20. Early visual evoked potentials are modulated by eye position in humans induced by whole body rotations

    Directory of Open Access Journals (Sweden)

    Petit Laurent

    2004-09-01

    Full Text Available Abstract Background To reach and grasp an object in space on the basis of its image cast on the retina requires different coordinate transformations that take into account gaze and limb positioning. Eye position in the orbit influences the image's conversion from retinotopic (eye-centered coordinates to an egocentric frame necessary for guiding action. Neuroimaging studies have revealed eye position-dependent activity in extrastriate visual, parietal and frontal areas that is along the visuo-motor pathway. At the earliest vision stage, the role of the primary visual area (V1 in this process remains unclear. We used an experimental design based on pattern-onset visual evoked potentials (VEP recordings to study the effect of eye position on V1 activity in humans. Results We showed that the amplitude of the initial C1 component of VEP, acknowledged to originate in V1, was modulated by the eye position. We also established that putative spontaneous small saccades related to eccentric fixation, as well as retinal disparity cannot explain the effects of changing C1 amplitude of VEP in the present study. Conclusions The present modulation of the early component of VEP suggests an eye position-dependent activity of the human primary visual area. Our findings also evidence that cortical processes combine information about the position of the stimulus on the retinae with information about the location of the eyes in their orbit as early as the stage of primary visual area.

  1. Early diagnosis of tongue malignancy using laser induced fluorescence spectroscopy technique

    Science.gov (United States)

    Patil, Ajeetkumar; Unnikrishnan V., K.; Ongole, Ravikiran; Pai, Keerthilatha M.; Kartha, V. B.; Chidangil, Santhosh

    2015-07-01

    Oral cancer together with pharyngeal cancer is the sixth most common malignancy reported worldwide and one with high mortality ratio among all malignancies [1]. Worldwide 450,000 new cases are estimated in 2014[2]. About 90% are a type of cancer called squamous cell carcinoma (SCC). SCC of the tongue is the most common oral malignancy accounting for approximately 40% of all oral carcinomas. One of the important factors for successful therapy of any malignancy is early diagnosis. Although considerable progress has been made in understanding the cellular and molecular mechanisms of tumorigenesis, lack of reliable diagnostic methods for early detection leading to delay in therapy is an important factor responsible for the increase in the mortality rate in various types of cancers. Spectroscopy techniques are extremely sensitive for the analysis of biochemical changes in cellular systems. These techniques can provide a valuable information on alterations that occur during the development of cancer. This is especially important in oral cancer, where "tumor detection is complicated by a tendency towards field cancerization, leading to multi-centric lesions" and "current techniques detect malignant change too late" [3], and "biopsies are not representative of the whole premalignant lesion". [4

  2. Early warning of orographically induced floods and landslides in Western Norway

    Science.gov (United States)

    Leine, Ann-Live; Wang, Thea; Boje, Søren

    2017-04-01

    In Western Norway, landslides and debris flows are commonly initiated by short-term orographic rainfall or intensity peaks during a prolonged rainfall event. In recent years, the flood warning service in Norway has evolved from being solely a flood forecasting service to also integrating landslides into its early warning systems. As both floods and landslides are closely related to the same hydrometeorological processes, particularly in small catchments, there is a natural synergy between monitoring flood and landslide risk. The Norwegian Flood and Landslide Hazard Forecasting and Warning Service issues regional landslide hazard warnings based on hydrological models, threshold values, observations and weather forecasts. Intense rainfall events and/or orographic precipitation that, under certain topographic conditions, significantly increase the risk of debris avalanches and debris floods are lately receiving more research focus from the Norwegian warning service. Orographic precipitation is a common feature in W-Norway, when moist and relatively mild air arrives from the Atlantic. Steep mountain slopes covered by glacial till makes the region prone to landslides, as well as flooding. The operational early warning system in Norway requires constant improvement, especially with the enhanced number of intense rainfall events that occur in a warming climate. Here, we examine different cases of intense rainfall events which have lead to landslides and debris flows, as well as increased runoff in fast responding small catchments. The main objective is to increase the understanding of the hydrometeorological conditions related to these events, in order to make priorities for the future development of the warning service.

  3. Repeated electroconvulsive seizure treatment in rats reduces inducibility of early growth response genes and hyperactivity in response to cocaine administration.

    Science.gov (United States)

    Park, Hong Geun; Kim, Se Hyun; Kim, Han Soo; Ahn, Yong Min; Kang, Ung Gu; Kim, Yong Sik

    2011-06-01

    Regulated expression of immediate early genes (IEGs) in the brain reflects neuronal activity in response to various stimuli and recruits specific gene programs involved in long-term neuronal modification and behavioral alterations. Repeated electroconvulsive seizure (ECS) treatment reduces the expression level of several IEGs, such as c-fos, which play important roles in psychostimulant-induced behavioral changes. In this study, we investigated the effects of repeated ECS treatment on the basal expression level of IEGs and its effects on cocaine-induced activation of IEGs and locomotor activity in rats. Repeated ECS treatment for 10days (E10×) reduced Egr1, Egr2, Egr3, and c-fos mRNA and protein levels in the rat frontal cortex at 24h after the last ECS treatment, and these changes were evident in the neuronal cells of the prefrontal cortex. In particular, downregulation of Egr1 and c-fos was evident until 5days after the last ECS treatment. Moreover, E10× pretreatment attenuated the cocaine-induced increase in Egr1, Egr2, and c-fos expression in the rat frontal cortex, whereas phosphorylation of ERK1/2, one of the representative upstream activators of these genes, increased significantly following cocaine treatment. Additionally, E10× pretreatment attenuated the increase in locomotor activity in response to a cocaine injection. In conclusion, repeated ECS treatment reduced the expression and inducibility of Egrs and c-fos, which could attenuate the response of the brain to psychostimulants. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Emergence, development, and maturity of the gonad of two species of chitons "sea cockroach" (Mollusca: Polyplacophora through the early life stages.

    Directory of Open Access Journals (Sweden)

    Omar Hernando Avila-Poveda

    Full Text Available This study describes and recognises, using histological and microscopical examinations on a morphometrical basis, several gonad traits through the early life stages of Chiton articulatus and C. albolineatus. Gonadal ontogenesis, gonad development stages, sexual differentiation, onset of the first sexual maturity, and growth sequences or "early life stages" were determined. In addition, allometry between lengths and body weight pooled for both sexes per each chiton were calculated using equation Y = aX(b . A total of 125 chitons (4≤TL≤40 mm, in total length "TL" were used. All allometric relations showed a strong positive correlation (r, close to 1, with b-values above three, indicating an isometric growth. Gonadal ontogenesis and gonad development stages were categorised into three periods ("Pw" without gonad, "Pe" gonad emergence, and "Pf" gonadal sac formed and four stages ("S0" gametocytogenesis, "S1" gametogenesis, "S2" mature, and "S3" spawning, respectively. Compound digital images were attained for each process. Periods and stages are overlapped among them and between species, with the following overall confidence intervals in TL: Pw 6.13-14.32 mm, Pe 10.32-16.93 mm, Pf 12.99-25.01 mm, S0 16.08-24.34 mm (females and 19.51-26.60 mm (males, S1 27.15-35.63 mm (females and 23.45-32.27 mm (males, S2 24.48-40.24 mm (females and 25.45-32.87 mm (males. Sexual differentiation (in S0 of both chitons occurs first as a female then as a male; although, males reach the onset of the first sexual maturity earlier than females, thus for C. articulatus males at 17 mm and females at 32 mm, and for C. albolineatus males at 23.5 mm and females at 28 mm, all in TL. Four early life stages (i.e., subjuvenile, juvenile, subadult, and adult are described and proposed to distinguish growth sequences. Our results may be useful to diverse disciplines, from developmental biology to fisheries management.

  5. Emergence, development, and maturity of the gonad of two species of chitons "sea cockroach" (Mollusca: Polyplacophora) through the early life stages.

    Science.gov (United States)

    Avila-Poveda, Omar Hernando; Abadia-Chanona, Quetzalli Yasú

    2013-01-01

    This study describes and recognises, using histological and microscopical examinations on a morphometrical basis, several gonad traits through the early life stages of Chiton articulatus and C. albolineatus. Gonadal ontogenesis, gonad development stages, sexual differentiation, onset of the first sexual maturity, and growth sequences or "early life stages" were determined. In addition, allometry between lengths and body weight pooled for both sexes per each chiton were calculated using equation Y = aX(b) . A total of 125 chitons (4≤TL≤40 mm, in total length "TL") were used. All allometric relations showed a strong positive correlation (r), close to 1, with b-values above three, indicating an isometric growth. Gonadal ontogenesis and gonad development stages were categorised into three periods ("Pw" without gonad, "Pe" gonad emergence, and "Pf" gonadal sac formed) and four stages ("S0" gametocytogenesis, "S1" gametogenesis, "S2" mature, and "S3" spawning), respectively. Compound digital images were attained for each process. Periods and stages are overlapped among them and between species, with the following overall confidence intervals in TL: Pw 6.13-14.32 mm, Pe 10.32-16.93 mm, Pf 12.99-25.01 mm, S0 16.08-24.34 mm (females) and 19.51-26.60 mm (males), S1 27.15-35.63 mm (females) and 23.45-32.27 mm (males), S2 24.48-40.24 mm (females) and 25.45-32.87 mm (males). Sexual differentiation (in S0) of both chitons occurs first as a female then as a male; although, males reach the onset of the first sexual maturity earlier than females, thus for C. articulatus males at 17 mm and females at 32 mm, and for C. albolineatus males at 23.5 mm and females at 28 mm, all in TL. Four early life stages (i.e., subjuvenile, juvenile, subadult, and adult) are described and proposed to distinguish growth sequences. Our results may be useful to diverse disciplines, from developmental biology to fisheries management.

  6. MRI to quantify early radiation-induced changes in the salivary glands.

    Science.gov (United States)

    Houweling, Antonetta C; Schakel, Tim; van den Berg, Cornelis A T; Philippens, Marielle E P; Roesink, Judith M; Terhaard, Chris H J; Raaijmakers, Cornelis P J

    2011-09-01

    We investigated radiation-induced changes in the salivary glands, 6 weeks after RT, using MRI. Eighteen oropharyngeal cancer patients were treated with salivary gland sparing IMRT. All patients received a 3T MRI exam before and 6 weeks after the end of RT, including a T(1)-weighted (T(1)w), a T(2)-weighted (T(2)w), and a dynamic contrast-enhanced (DCE) MRI. For both time points separately, the parotid and submandibular glands were delineated on the MR images. Differences in median signal intensity and signal variation within the glands were tested for significance. Correlations were studied between the MR changes and the planned RT dose. The volume of the glands reduced significantly by 25%. The T(1)w signal decreased by 10% and the T(2)w signal increased by 23%. The k(ep) value decreased, while the v(e) increased. A correlation of the changes in T(2)w signal with the mean dose was found in both glands. Overall radiation-induced changes and volume loss were observed in the parotid and submandibular gland using MR. The observed differences indicated an increased water content such as found in oedema. The overall changes could be related to the mean dose, with a slightly greater impact in the high dose area. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Single Silver Nanoparticle Instillation Induced Early and Persisting Moderate Cortical Damage in Rat Kidneys

    Directory of Open Access Journals (Sweden)

    Elisa Roda

    2017-10-01

    Full Text Available The potential toxic effects of silver nanoparticles (AgNPs, administered by a single intratracheal instillation (i.t, was assessed in a rat model using commercial physico-chemical characterized nanosilver. Histopathological changes, overall toxic response and oxidative stress (kidney and plasma protein carbonylation, paralleled by ultrastructural observations (TEM, were evaluated to examine renal responses 7 and 28 days after i.t. application of a low AgNP dose (50 µg/rat, compared to an equivalent dose of ionic silver (7 µg AgNO3/rat. The AgNPs caused moderate renal histopathological and ultrastructural alteration, in a region-specific manner, being the cortex the most affected area. Notably, the bulk AgNO3, caused similar adverse effects with a slightly more marked extent, also triggering apoptotic phenomena. Specifically, 7 days after exposure to both AgNPs and AgNO3, dilatation of the intercapillary and peripheral Bowman’s space was observed, together with glomerular shrinkage. At day 28, these effects still persisted after both treatments, accompanied by an additional injury involving the vascular component of the mesangium, with interstitial micro-hemorrhages. Neither AgNPs nor AgNO3 induced oxidative stress effects in kidneys and plasma, at either time point. The AgNP-induced moderate renal effects indicate that, despite their benefits, novel AgNPs employed in consumer products need exhaustive investigation to ensure public health safety.

  8. Fatal Abdominal Compartment Syndrome Due to Severe Triglyceride-Induced Pancreatitis in Early Pregnancy.

    Science.gov (United States)

    Chibber, Tamanna; Gibson, Paul S

    2017-10-03

    Serum levels of maternal lipids rise physiologically in normal pregnancy, and women with underlying hypertriglyceridemia may experience dramatic elevations which place them at risk for pancreatitis. We describe the case of a woman with severe familial hypertriglyceridemia and prior pancreatitis who discontinued her lipid-lowering therapy early in pregnancy. She promptly developed severe abdominal pain and was hospitalized with acute pancreatitis during the late first trimester. Despite aggressive medical treatment and critical care monitoring, she developed abdominal compartment syndrome (ACS) with associated acute renal failure, which progressed to cardiorespiratory failure and was ultimately fatal. ACS is an alarming complication of acute pancreatitis that has been poorly studied in pregnancy. Copyright © 2017 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

  9. Early life history and habitat ecology of estuarine fishes: responses to natural and human induced change

    Directory of Open Access Journals (Sweden)

    Kenneth Able

    2015-12-01

    Full Text Available Our understanding of the early life history of fishes and their habitats has proceeded from basic natural history to ecology, but we often need to return to natural history to address deficiencies in conceptual and quantitative models of ecosystems. This understanding is further limited by the complex life history of fishes and the lack of appreciation of shifting baselines in estuaries. These inadequacies are especially evident when we try to address the effects of human influences, e.g. fishing, urbanization, and climate change. Often our baselines are inadequate or inaccurate. Our work has detected these along the coasts of the U.S. in extensive time series of larval fish ingress into estuaries, studies of the effects of urbanization, and responses to catastrophes such as the BP oil spill. Long-term monitoring, especially, continues to provide critical insights

  10. Florfenicol induces early embryonic death in eggs collected from treated hens.

    Science.gov (United States)

    Al-Shahrani, S; Naidoo, V

    2015-08-18

    Florfenicol, a commonly used veterinary antibiotic, was reported to have caused a severe drop in egg hatchability following its off-label use on a broiler breeder farm in South Africa. According to the pharmacovigilance report, hatchability dropped by 80 % for up to a week following a five day course at 10 mg/kg (both males and females treated metaphylactically) to manage an Escherichia coli infection. While mammalian toxicity studies indicate the potential for early embryonic death in utero or testicular damage, no literature is available on the avian toxicity of florfenicol. For this study we investigated the effects of florfenicol at various doses from 10 to 90 mg/kg on the egg hatchability in a breeder flock we kept and established under controlled conditions, with the same cockerels and hens being exposed in a phased manner. Following five days of oral exposure, no toxic signs were evident in any of the cockerels or hens treated at doses up to 90 mg/kg. Treatment of only the cockerels had no effect on egg hatchability, while treatment of only the hens at doses of 60 and 90 mg/kg resulted in decreased hatchability of 0 % in comparison to 70 % of the control as early 24 h after treatment. In all cases, decreased hatchability was associated with embryonic death at 5 days of development. The toxic effects of florfenicol were completely reversible with comparable hatchability being present by day 4 post-treatment withdrawal. Toxicity correlated with total egg florfenicol concentrations with an LC50 of 1.07 μg/g. Florfenicol appears to be toxic to the developing chick embryo at around day 5 of incubation, in the absence of related toxicity in the hen or cockerel.

  11. Early Signs of Oxidative Stress Induced by Environmental Pollutants and Radiation Exposure in Rats

    International Nuclear Information System (INIS)

    Noaman, E.; Gharib, O.A.

    2005-01-01

    The current study examines the early effects of whole body y-radiation exposure with single dose of (6.5 Gy) and acute single dose (2250 mg/Kg b. wt.) of 1,4-dioxane, which is considered the most common environmental contaminants used. Rats were sacrificed after one and twenty-four h after radiation exposure and/or 1,4-dioxane administration. The significant elevation in lipid peroxidation concentration, measured as malonaldehydoyl (MDA) was observed only after 24 h in radiation/1,4-dioxane group. The results showed that Glutathione (GSH) concentration was significantly decreased after 1 h followed by enhancement significantly after 24 h in radiation/1,4-dioxane group. Elevation in superoxide dismutase (SOD) activity was detected early (after 1 h) and continued elevation after twenty-four h recorded highly significant increase in radiation and/or 1,4-dioxane groups. The hematological parameters revealed more or less non-significant changes in red blood cells (RBCs) counts, hemoglobin concentration (Hbg) and haematocrit value (PVC), while significant increase in white blood cell counts (WBCs) count after one and 24 h post irradiation with or without 1,4-dioxane administration were recorded. In general 1,4-dioxane acted as a debilitator, which enhanced the overall effect of ionizing radiation when applied as the second insult. Antioxidants are the body's primary defense against free radicals and reactive oxygen species (ROS). Free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membrane, nucleotides, in DNA and critical sulfhydryl bonds in protein. The over production of ROS in both intra-and extra cellular spaces upon exposure of living subjects to certain chemicals, radiation or local tissue inflammation, results in oxidative stress defined as the imbalance between pro- oxidation and antioxidants

  12. Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-α and prevents early alcohol-induced liver injury in mice

    DEFF Research Database (Denmark)

    Ge, Xiadong; Leung, Tung-Ming; Arriazu, Elena

    2014-01-01

    , tumor necrosis factor-α (TNFα) production, and liver injury. Since OPN is protective for the intestinal mucosa, we postulated that enhancing OPN expression in the liver and consequently in the blood and/or in the gut could protect from early alcohol-induced liver injury. Wild-type (WT), OPN knockout...... score, and the number of macrophages and TNFα+ cells. To establish if OPN could limit LPS availability and its noxious effects in the liver, binding studies were performed. OPN showed binding affinity for LPS which prevented macrophage activation, reactive oxygen, and nitrogen species generation...... by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining, and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower alanine aminotransferase (ALT) activity, hepatocyte ballooning degeneration, LPS levels, the inflammation...

  13. Early infancy-onset stimulation-induced myoclonic seizures in three siblings with inherited glycosylphosphatidylinositol (GPI) anchor deficiency.

    Science.gov (United States)

    Mogami, Yukiko; Suzuki, Yasuhiro; Murakami, Yoshiko; Ikeda, Tae; Kimura, Sadami; Yanagihara, Keiko; Okamoto, Nobuhiko; Kinoshita, Taroh

    2018-02-01

    Inherited glycosylphosphatidylinositol anchor deficiency causes a variety of clinical symptoms, including epilepsy, however, little information is available regarding seizures as a symptom. We report three siblings with inherited glycosylphosphatidylinositol anchor deficiency with PIGL gene mutations. The phenotypes of the subjects were not consistent with CHIME syndrome or Mabry syndrome, as reported in previous studies. All shared some clinical manifestations, including transient apnoea as neonates, dysmorphic facial features, and intellectual disability. Between one week and 3 months of life, all patients developed myoclonic seizures. Myoclonic jerks were easily evoked by sudden unexpected acoustic or tactile stimuli. None showed elevation of serum alkaline phosphatase. Vitamin B 6 was given to one of the three siblings, but failed to suppress seizures. The presence of early infancy-onset stimulation-induced myoclonic seizures combined with dysmorphic facial features should lead physicians to consider the possibility of inherited glycosylphosphatidylinositol anchor deficiency.

  14. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model.

    Science.gov (United States)

    Li, Jian; Niu, Jian-Zhao; Wang, Ji-Feng; Li, Yu; Tao, Xiao-Hua

    2005-11-07

    To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-mum thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, Pportal vein were significantly higher in model group than those in the control group. Plasma HA (129.97+/-16.10 vs 73.09+/-2.38 ng/mL, Pmodel group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased remarkably and perisinusoids were almost surrounded by ColIII. Immunohistochemical staining showed that ColIV protein level (0.130+/-0.007 vs 0.032+/-0.004, Pprotein level (0.152+/-0.005 vs 0.029+/-0.005, Pmodel group. MMP-2 protein expression (2.306+/-1.089 vs 0.612+/-0.081, Pprotein expression (3.015+/-1.364 vs 0.446+/-0.009, Pmodel group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, Pportal hypertension in rats.

  15. Alterations in gene expression during fasting-induced atresia of early secondary ovarian follicles of coho salmon, Oncorhynchus kisutch.

    Science.gov (United States)

    Yamamoto, Yoji; Luckenbach, J Adam; Young, Graham; Swanson, Penny

    2016-11-01

    Molecular processes that either regulate ovarian atresia or are consequences of atresia are poorly understood in teleost fishes. We hypothesized that feed restriction that perturbs normal ovarian growth and induces follicular atresia would alter ovarian gene expression patterns. Previtellogenic, two-year old coho salmon (Oncorhynchus kisutch) were subjected to prolonged fasting to induce atresia or maintained on a normal feeding schedule that would promote continued ovarian development. To identify genes that were specifically up- or down-regulated during oocyte growth in healthy, growing fish compared to fasted fish, reciprocal suppression subtractive hybridization (SSH) cDNA libraries were generated using ovaries from fed and fasted animals. Differential expression of genes identified by SSH was confirmed with quantitative PCR. The SSH library representing genes elevated in ovaries of fed fish relative to those of fasted fish contained steroidogenesis-related genes (e.g., hydroxy-delta-5-steroid dehydrogenase), Tgf-beta superfamily members (e.g., anti-Mullerian hormone) and cytoskeletal intermediate filament proteins (e.g., type I keratin s8). Overall, these genes were associated with steroid production, cell proliferation and differentiation, and ovarian epithelialization. The library representing genes elevated in ovaries of fasted fish relative to fed fish contained genes associated with apoptosis (e.g., programmed cell death protein 4), cortical alveoli (e.g., alveolin), the zona pellucida (e.g., zona pellucida protein c), and microtubules (e.g., microtubule associated protein tau). Elevated expression of this suite of genes was likely associated with the initiation of atresia and/or a reduced rate of follicle development in response to fasting. This study revealed ovarian genes involved in normal early secondary oocyte growth and potential early markers of atresia. Published by Elsevier Inc.

  16. Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring.

    Science.gov (United States)

    Mao, Zhenxing; Xia, Wei; Chang, Huailong; Huo, Wenqian; Li, Yuanyuan; Xu, Shunqing

    2015-11-04

    Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Broberg, Brian V; Madsen, Kristoffer H; Plath, Niels

    2013-01-01

    Better animal models are needed to aid the development of new medications to alleviate the cognitive deficits associated with schizophrenia. Growing evidence suggests neurodevelopmental insults and disturbances in NMDA receptor (NMDAR) signaling to be involved in the schizophrenia etiology. Acute...... administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20mg/kg PCP on postnatal days 7, 9, and 11 (neo......PCP), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain...

  18. Laser Induced Breakdown Spectroscopy of meteorites as a probe of the early solar system

    Science.gov (United States)

    Dell'Aglio, M.; De Giacomo, A.; Gaudiuso, R.; De Pascale, O.; Longo, S.

    2014-11-01

    This paper presents an evaluation of Laser Induced Breakdown Spectroscopy (LIBS) as a technique for gathering data relevant to Solar System geophysics. Two test cases were demonstrated: elemental analysis of chondrules in a chondrite meteorite, and space- resolved analysis of the interface between kamacite and taenite crystals in an octahedrite iron meteorite. In particular most major and minor elements (Fe, Mg, Si, Ti, Al, Cr, Mn, Ca, Fe, Ni, Co) in Sahara 98222 (chondrite) and its chondrules, as well as the profile of Ni content in Toluca (iron meteorite), were determined with the Calibration Free (CF) method. A special attention was devoted to exploring the possibilities offered by variants of the basic technique, such as the use of Fe I Boltzmann distribution as an intensity calibration method of the spectroscopic system, and the use of spatially resolved analysis.

  19. Algal Toxin Azaspiracid-1 Induces Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry

    Directory of Open Access Journals (Sweden)

    Linda V. Hjørnevik

    2015-12-01

    Full Text Available Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to most cells and cell lines, little is known about its biological target(s. A rat PC12 cell line, commonly used as a model for the peripheral nervous system, was used to study the neurotoxicological effects of azaspiracid-1. Azaspiracid-1 induced differentiation-related morphological changes followed by a latter cell death. The differentiated phenotype showed peripherin-labelled neurite-like processes simultaneously as a specific isoform of peripherin was down-regulated. The precise mechanism behind this down-regulation remains uncertain. However, this study provides new insights into the neurological effects of azaspiracid-1 and into the biological significance of specific isoforms of peripherin.

  20. Myxoviruses do not induce non-specific alterations in membrane permeability early on in infection

    International Nuclear Information System (INIS)

    Foster, K.A.; Micklem, K.J.; Bogomolova, N.N.; Boriskin, Y.S.; Pasternak, C.A.

    1983-01-01

    The permeability characteristics of cells infected with myxoviruses have been studied by measuring the concentrative uptake of nutrients, the concentration of intracellular K + , and the maintenance of the Na + gradient across the plasma membrane. Cells either show no change at all (Sendai virus-infected BHK cells and measles virus-infected Vero cells) or they show a decreased ability to concentrate nutrients, while intracellular K + and the Na + gradient remain unchanged (Sendai and influenza virus-infected L-1210 cells, measles virus-infected lymphocytes and mumps virus-infected L-41 cells). In no case, therefore, was a change observed that resembles the non-specific increase in membrane permeability induced by haemolytic paramyxoviruses (35, 42) or the non-specific membrane leakiness postulated to take place in infected cells (8, 9). A preliminary account of some of these findings has been presented (39)

  1. Menses resumption after cancer treatment-induced amenorrhea occurs early or not at all.

    Science.gov (United States)

    Jacobson, Melanie H; Mertens, Ann C; Spencer, Jessica B; Manatunga, Amita K; Howards, Penelope P

    2016-03-01

    To identify factors associated with cancer treatment-induced amenorrhea and time to return of menses. Population-based cohort study. Not applicable. Female cancer survivors who were diagnosed with cancer between the ages of 20 and 35 and were at least 2 years postdiagnosis at the time of recruitment (median = 7 years; interquartile range, 5-11). None. Amenorrhea (≥6 months without menses) and resumption of menses. After excluding women with hysterectomies before cancer diagnosis, 1,043 women were eligible for analysis. Amenorrhea occurred in 31.6% of women. Among women treated with chemotherapy (n = 596), older age at diagnosis (30-35 vs. 20-24 years: adjusted odds ratio [aOR] = 2.37; 95% confidence interval [CI], 1.30, 4.30) and nulligravidity (vs. gravid: aOR = 1.50; 95% CI, 1.02, 2.21) were risk factors for amenorrhea. Among amenorrheic women, menses resumed in most (70.0%), and resumption occurred within 2 years of treatment for 90.0% of women. Survivors of breast cancer were more likely to resume menses at times greater than 1 year compared with lymphoma and pelvic-area cancers. Women diagnosed at older ages, those exposed to chemotherapy, and those exposed to any radiation experienced longer times to return of menses. Women who were older at diagnosis were more likely to have irregular cycles when menses returned. Treatment-induced amenorrhea is common in cancer survivors, although most women resume menses within 2 years. However, once resumed, older women are more likely to have irregular cycles. Age at diagnosis and pregnancy history affect the risk of amenorrhea. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Early cardiac changes induced by a hypercaloric Western-type diet in "subclinical" obesity.

    Science.gov (United States)

    Gonçalves, Nádia; Silva, Ana Filipa; Rodrigues, Patrícia Gonçalves; Correia, Eugénia; Moura, Cláudia; Eloy, Catarina; Roncon-Albuquerque, Roberto; Falcão-Pires, Inês; Leite-Moreira, Adelino F

    2016-03-15

    "Obesity cardiomyopathy" effects have been widely described; however, the specific contribution of metabolic changes and altered adipokine secretion are still uncharacterized. Moreover, a diagnosis based on body mass index might not be the most accurate to identify increased adiposity and its outcomes. In this study, we aimed to determine the impact of a Western-type diet [hypercaloric diet (HCD)] ingestion on biventricular structure and function, as well as the metabolic and endocrine changes that occur before the establishment of overt obesity. Wistar rats were fed for 6 wk with a regular diet or HCD. At the end of the protocol, metabolic tests, cardiac structure, and functional evaluation were performed, and blood and tissue samples collected to perform histological, molecular biology, and functional studies. The animals that ingested the HCD presented increased adiposity and larger adipocyte cross-sectional area, but similar body weight compared with the regular diet group. At the cardiac level, HCD induced biventricular cardiomyocyte hypertrophy, fibrosis, increased stiffness, and impaired relaxation. Galectin-3 plasma expression was likewise elevated in the same animals. The nutritional modulation also altered the secretory pattern of the adipose tissue, originating a proinflammatory systemic environment. In this study, we observed that before "clinical" overweight or frank obesity is established, the ingestion of a HCD-induced cardiac remodeling manifests by increased biventricular stiffness and diastolic dysfunction. The mechanism triggering the cardiac alterations appears to be the proinflammatory environment promoted by the adipose tissue dysfunction. Furthermore, galectin-3, a profibrotic molecule, might be a potential biomarker for the myocardial alterations promoted by the HCD before overweight or obesity. Copyright © 2016 the American Physiological Society.

  3. Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice.

    Science.gov (United States)

    Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Sly, Peter D; Larcombe, Alexander N

    2016-01-01

    Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.

  4. Investigations of hormones during early abortion induced by prostaglandin Fsub(2α) and 15(S)-methyl-PGFsub(2α)

    International Nuclear Information System (INIS)

    Seifert, B.; Liedtke, M.P.; Brockmann, J.; Beissert, M.; Gstoettner, H.; Alexander, H.; Herter, U.

    1978-01-01

    In early pregnancy up the 7th week of pregnancy PGFsub(2α) was infused and 15(S)-methyl-PGFsub(2α) was applied i.m. to induce menstruation in 20 or 19 cases, respectively. In the tested form of application 15(S)-methyl-PGFsub(2α) is effective in 89 per cent of the cases and in 74 per cent complete abortion was achieved. PGFsub(2α) produced bleeding in 80 per cent only and complete abortion in 55 per cent. The differences in these two groups were not statistically significant. The steroid hormones estradiol and progesterone decrease in a successful application of PGs for induction of abortion and reach a value of 75 per cent at the onset of bleeding. The LH concentration in plasma becomes smaller too. In some cases there is a temporary increase in hormones shortly after starting treatment. The results could indicate that the considerable decrease in hormones before the onset of bleeding might be caused by an alteration of the corpus luteum, which is effective during early pregnangy. (author)

  5. Asymmetric distribution of hypoxia-inducible factor α regulates dorsoventral axis establishment in the early sea urchin embryo.

    Science.gov (United States)

    Chang, Wei-Lun; Chang, Yi-Cheng; Lin, Kuan-Ting; Li, Han-Ru; Pai, Chih-Yu; Chen, Jen-Hao; Su, Yi-Hsien

    2017-08-15

    Hypoxia signaling is an ancient pathway by which animals can respond to low oxygen. Malfunction of this pathway disturbs hypoxic acclimation and can result in various diseases, including cancers. The role of hypoxia signaling in early embryogenesis remains unclear. Here, we show that in the blastula of the sea urchin Strongylocentrotus purpuratus , hypoxia-inducible factor α (HIFα), the downstream transcription factor of the hypoxia pathway, is localized and transcriptionally active on the future dorsal side. This asymmetric distribution is attributable to its oxygen-sensing ability. Manipulations of the HIFα level entrained the dorsoventral axis, as the side with the higher level of HIFα tends to develop into the dorsal side. Gene expression analyses revealed that HIFα restricts the expression of nodal to the ventral side and activates several genes encoding transcription factors on the dorsal side. We also observed that intrinsic hypoxic signals in the early embryos formed a gradient, which was disrupted under hypoxic conditions. Our results reveal an unprecedented role of the hypoxia pathway in animal development. © 2017. Published by The Company of Biologists Ltd.

  6. Evaluation of early changes induced by diuron in the rat urinary bladder using different processing methods for scanning electron microscopy.

    Science.gov (United States)

    Fava, Rafaela Marono; Ferragut Cardoso, Ana Paula; da Rocha, Mitscheli Sanches; Nascimento E Pontes, Merielen Garcia; de Camargo, João Lauro Viana; de Oliveira, Maria Luiza Cotrim Sartor

    2015-07-03

    Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide carcinogenic to the rat urinary bladder at high dietary levels. The suggested non-genotoxic mode of action (MOA) of diuron encompasses cytotoxicity and necrosis followed by regenerative hyperplasia. Prenecrotic swollen cells as observed under scanning electron microscopy (SEM) have been reported as early morphological alterations, putatively related to diuron cytotoxicity. However, these changes were not observed in a previous SEM study conducted in this laboratory. This study evaluated whether these early alterations are actually due to diuron cytotoxicity or artifacts related to different processing methods used for SEM analysis. Male Wistar rats were fed ad libitum with basal diet, 7.1% sodium saccharin (NaS) or 2.500ppm diuron for seven days or 15 weeks. The urinary bladders were processed for histological and labeling indices examinations and for SEM using two different processing methods. The incidence of simple hyperplasia after 15 weeks of exposure to diuron or to NaS was significantly increased. By SEM, the incidences and severity of lesions were significantly increased in the diuron group independently of exposure time. The different SEM processing methods used allowed for visualization of swollen superficial cells after seven days of diuron exposure. Probably the absence these cells in a previous study was due to the use very few animals. Our results support the hypothesis that the swollen cell is an early key event due to diuron-induced cytotoxicity and is the result of a degenerative process involved in the non-genotoxic carcinogenic mode of action of high doses of diuron. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Evaluation of early changes induced by diuron in the rat urinary bladder using different processing methods for scanning electron microscopy

    International Nuclear Information System (INIS)

    Fava, Rafaela Marono; Ferragut Cardoso, Ana Paula; Sanches da Rocha, Mitscheli; Nascimento e Pontes, Merielen Garcia; Viana de Camargo, João Lauro; Cotrim Sartor de Oliveira, Maria Luiza

    2015-01-01

    Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide carcinogenic to the rat urinary bladder at high dietary levels. The suggested non-genotoxic mode of action (MOA) of diuron encompasses cytotoxicity and necrosis followed by regenerative hyperplasia. Prenecrotic swollen cells as observed under scanning electron microscopy (SEM) have been reported as early morphological alterations, putatively related to diuron cytotoxicity. However, these changes were not observed in a previous SEM study conducted in this laboratory. This study evaluated whether these early alterations are actually due to diuron cytotoxicity or artifacts related to different processing methods used for SEM analysis. Male Wistar rats were fed ad libitum with basal diet, 7.1% sodium saccharin (NaS) or 2.500 ppm diuron for seven days or 15 weeks. The urinary bladders were processed for histological and labeling indices examinations and for SEM using two different processing methods. The incidence of simple hyperplasia after 15 weeks of exposure to diuron or to NaS was significantly increased. By SEM, the incidences and severity of lesions were significantly increased in the diuron group independently of exposure time. The different SEM processing methods used allowed for visualization of swollen superficial cells after seven days of diuron exposure. Probably the absence these cells in a previous study was due to the use very few animals. Our results support the hypothesis that the swollen cell is an early key event due to diuron-induced cytotoxicity and is the result of a degenerative process involved in the non-genotoxic carcinogenic mode of action of high doses of diuron

  8. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Wyrobek, Andrew J.

    2009-01-18

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

  9. Meteorite Impact-Induced Rapid NH3 Production on Early Earth: Ab Initio Molecular Dynamics Simulation

    Science.gov (United States)

    Shimamura, Kohei; Shimojo, Fuyuki; Nakano, Aiichiro; Tanaka, Shigenori

    2016-12-01

    NH3 is an essential molecule as a nitrogen source for prebiotic amino acid syntheses such as the Strecker reaction. Previous shock experiments demonstrated that meteorite impacts on ancient oceans would have provided a considerable amount of NH3 from atmospheric N2 and oceanic H2O through reduction by meteoritic iron. However, specific production mechanisms remain unclear, and impact velocities employed in the experiments were substantially lower than typical impact velocities of meteorites on the early Earth. Here, to investigate the issues from the atomistic viewpoint, we performed multi-scale shock technique-based ab initio molecular dynamics simulations. The results revealed a rapid production of NH3 within several picoseconds after the shock, indicating that shocks with greater impact velocities would provide further increase in the yield of NH3. Meanwhile, the picosecond-order production makes one expect that the important nitrogen source precursors of amino acids were obtained immediately after the impact. It was also observed that the reduction of N2 proceeded according to an associative mechanism, rather than a dissociative mechanism as in the Haber-Bosch process.

  10. Probing the early stages of shock-induced chondritic meteorite formation at the mesoscale

    Science.gov (United States)

    Rutherford, Michael E.; Chapman, David J.; Derrick, James G.; Patten, Jack R. W.; Bland, Philip A.; Rack, Alexander; Collins, Gareth S.; Eakins, Daniel E.

    2017-05-01

    Chondritic meteorites are fragments of asteroids, the building blocks of planets, that retain a record of primordial processes. Important in their early evolution was impact-driven lithification, where a porous mixture of millimetre-scale chondrule inclusions and sub-micrometre dust was compacted into rock. In this Article, the shock compression of analogue precursor chondrite material was probed using state of the art dynamic X-ray radiography. Spatially-resolved shock and particle velocities, and shock front thicknesses were extracted directly from the radiographs, representing a greatly enhanced scope of data than could be measured in surface-based studies. A statistical interpretation of the measured velocities showed that mean values were in good agreement with those predicted using continuum-level modelling and mixture theory. However, the distribution and evolution of wave velocities and wavefront thicknesses were observed to be intimately linked to the mesoscopic structure of the sample. This Article provides the first detailed experimental insight into the distribution of extreme states within a shocked powder mixture, and represents the first mesoscopic validation of leading theories concerning the variation in extreme pressure-temperature states during the formation of primordial planetary bodies.

  11. MMP-2 Plays an Important Role During the Early Acute Developmental Phase of Oligofructose-Induced Equine Laminitis

    Directory of Open Access Journals (Sweden)

    Li Xinran

    2015-04-01

    Full Text Available The study was conducted on 24 Mongolian horses, with oligofructose-induced equine laminitis (10 g/kg b.w.. The objective of the study was to investigate the relationships among matrix metalloproteinase 2 (MMP-2, P38 mitogen-activated protein kinases (P38 MAPK, tissue inhibitor of metalloproteinase 2 (TIMP-2, lipopolysaccharides (LPS, and tumour necrosis factor-α (TNF-α during acute developmental phase of laminitis, and to determine whether there are any characteristic tendencies. Moreover, plasma concentrations of LPS and TNF-α were measured in order to determine the time of leukocytes’ activation. Eleven of the 12 horses showed clinical signs of laminitis. The contents of MMP-2 and P38 MAPK increased significantly from 8 h to 64 h, and the content of TIMP-2 decreased significantly at the same time. Plasma LPS concentrations increased significantly between 8 h and 20 h and reached a peak of 0.024 ± 0.009 EU/mL (equivalent to 3.04 ± 1.19 pg/mL at 12 h. TNF-α concentration increased between 20 h and 36 h. This data indicates that MMP-2 plays an important role during the early acute developmental phase of oligofructose-induced equine laminitis.

  12. Induced Genome-Wide Binding of Three Arabidopsis WRKY Transcription Factors during Early MAMP-Triggered Immunity.

    Science.gov (United States)

    Birkenbihl, Rainer P; Kracher, Barbara; Somssich, Imre E

    2017-01-01

    During microbial-associated molecular pattern-triggered immunity (MTI), molecules derived from microbes are perceived by cell surface receptors and upon signaling to the nucleus initiate a massive transcriptional reprogramming critical to mount an appropriate host defense response. WRKY transcription factors play an important role in regulating these transcriptional processes. Here, we determined on a genome-wide scale the flg22-induced in vivo DNA binding dynamics of three of the most prominent WRKY factors, WRKY18, WRKY40, and WRKY33. The three WRKY factors each bound to more than 1000 gene loci predominantly at W-box elements, the known WRKY binding motif. Binding occurred mainly in the 500-bp promoter regions of these genes. Many of the targeted genes are involved in signal perception and transduction not only during MTI but also upon damage-associated molecular pattern-triggered immunity, providing a mechanistic link between these functionally interconnected basal defense pathways. Among the additional targets were genes involved in the production of indolic secondary metabolites and in modulating distinct plant hormone pathways. Importantly, among the targeted genes were numerous transcription factors, encoding predominantly ethylene response factors, active during early MTI, and WRKY factors, supporting the previously hypothesized existence of a WRKY subregulatory network. Transcriptional analysis revealed that WRKY18 and WRKY40 function redundantly as negative regulators of flg22-induced genes often to prevent exaggerated defense responses. © 2016 American Society of Plant Biologists. All rights reserved.

  13. Translational control of InsP3-induced chromatin condensation during the early cell cycles of sea urchin embryos.

    Science.gov (United States)

    Twigg, J; Patel, R; Whitaker, M

    1988-03-24

    The cycles of DNA synthesis and chromatin condensation in dividing cells are controlled by signals from the cytoplasm. Changes in the concentration of free calcium (Cai) in the cytoplasm control a variety of cellular functions and it has thus been suggested that observed variations in Cai during the cell cycle may be the cytoplasmic signal that co-ordinates nuclear and cytoplasmic division. We show here that increases in Cai induced by the calcium-releasing second messenger inositol 1,4,5-triphosphate (Ins(1,4,5)P3), or by calcium buffers, cause premature chromatin condensation and breakdown of the nuclear envelope in sea urchin (Lytechinus pictus) early embryos. Both natural and induced chromatin condensation are prevented by calcium chelators. The nucleus becomes sensitive to the Cai signal 45 min after fertilization, but remains insensitive if protein synthesis is prevented. Our experiments demonstrate that Cai regulates the behaviour of the nucleus during the cell cycle, suggest that Ins(1,4,5)P3 is a cell cycle messenger and indicate that there is an interaction between the protein and ionic signals that control the state of chromatin during the cell cycle.

  14. Early-life exposure to bisphenol a induces liver injury in rats involvement of mitochondria-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Wei Xia

    Full Text Available Exposure to bisphenol A (BPA, a monomer widely used to manufacture polycarbonate plastics, has been reported to be associated with abnormalities of liver function and hepatic damage. However, the molecular mechanism under the pathogenesis of hepatic injury is unclear. In this study, the effect of perinatal exposure to BPA at the reference dose of 50 µg/kg/day on the apoptotic index in the liver of rat offspring was investigated. Increased levels of ALT and enhanced cell apoptosis were observed in the liver of rat offspring at 15 and 21 weeks, and significantly increased activity of caspase-3 and caspase-9 and elevated levels of cytochrome c were also confirmed. In addition, significant change in the expression levels of Bcl-2 and Bax were found in BPA-treated offspring at 21 weeks. For in vitro experiments, liver mitochondria were isolated from neonatal rats and were treated with BPA. BPA treatment led to a significant increase in mitochondrial permeability transition. Moreover, the supernatant from BPA-treated mitochondria significantly increased apoptotic changes in nuclei isolated from liver tissue. In conclusion, the study demonstrates that BPA induces mitochondria-mediated apoptosis in hepatic cells, which may contribute to long-term hepatotoxicity induced by early-life exposure to BPA.

  15. Hematologic emergencies

    Directory of Open Access Journals (Sweden)

    Daniele Vallisa

    2012-01-01

    Full Text Available In recent years, the surprising progress made in other areas of hematology (advances in the understanding of leukemogenesis, improved transplant techniques has been conspicuously absent in the management of hematologic emergencies. And yet, every step toward greater knowledge, every new treatment option will be of little value unless we are able to manage the acute complications of hematologic diseases. These complications are better defined as hematologic emergencies, and they are characterized by a high rate of mortality. This review is based on a search of the literature that was initially confined to articles published in the journal Hematology from 2000 to 2009. The search was then extended to the Cochrane Library and to Pub Med in February 2010 with the following Keywords emergencies; urgencies; hematology. The same key words were employed in a search of the archives of Blood and the New England Journal of Medicine from 2000 to 2010. The results confirm that hematologic emergencies can be caused by hematologic malignancies as well as by non-neoplastic hematologic diseases. Within the former category; this review examines the causes; manifestations; treatment and prevention of disseminated intravascular coagulation; superior vena caval syndrome; spinal cord compression; tumor lysis syndrome; hyperleukocytosis; and hypercalcemia. We also review emergency situations associated with non-neoplatic haematological diseases; such as thrombotic thrombocytopenic purpura; drug-induced hemolytic anemia; and acute sickle-cell crisis.

  16. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  17. Imaging plant cell death: GFP-Nit1 aggregation marks an early step of wound and herbicide induced cell death

    Directory of Open Access Journals (Sweden)

    Somerville Chris R

    2005-03-01

    Full Text Available Abstract Background A great deal is known about the morphological endpoints of plant cell death, but relatively little is known about its sequence of events and / or its execution at the biochemical level. Live cell imaging using GFP-tagged markers is a powerful way to provide dynamic portraits of a cellular process that can in turn provide a descriptive foundation valuable for future biochemical and genetic investigations. Results While characterizing a collection of random GFP-protein fusion markers we discovered that mechanical wounding induces rapid aggregation of a GFP-Nitrilase 1 fusion protein in Arabidopsis cells directly abutting wound sites. Time-lapse imaging of this response shows that the aggregation occurs in cells that subsequently die 30 – 60 minutes post-wounding, indicating that GFP-Nit1 aggregation is an early marker of cell death at wound sites. Time-lapse confocal imaging was used to characterize wound-induced cell death using GFP-Nit1 and markers of the nucleus and endoplasmic reticulum. These analyses provide dynamic portraits of well-known death-associated responses such as nuclear contraction and cellular collapse and reveal novel features such as nuclear envelope separation, ER vesiculation and loss of nuclear-lumen contents. As a parallel system for imaging cell death, we developed a chemical method for rapidly triggering cell death using the herbicides bromoxynil or chloroxynil which cause rapid GFP-Nit1 aggregation, loss of nuclear contents and cellular collapse, but not nuclear contraction, separating this response from others during plant cell death. Conclusion Our observations place aggregation of Nitrilase 1 as one of the earliest events associated with wound and herbicide-induced cell death and highlight several novel cellular events that occur as plant cells die. Our data create a detailed descriptive framework for future investigations of plant cell death and provide new tools for both its cellular and

  18. Imaging plant cell death: GFP-Nit1 aggregation marks an early step of wound and herbicide induced cell death

    Science.gov (United States)

    Cutler, Sean R; Somerville, Chris R

    2005-01-01

    Background A great deal is known about the morphological endpoints of plant cell death, but relatively little is known about its sequence of events and / or its execution at the biochemical level. Live cell imaging using GFP-tagged markers is a powerful way to provide dynamic portraits of a cellular process that can in turn provide a descriptive foundation valuable for future biochemical and genetic investigations. Results While characterizing a collection of random GFP-protein fusion markers we discovered that mechanical wounding induces rapid aggregation of a GFP-Nitrilase 1 fusion protein in Arabidopsis cells directly abutting wound sites. Time-lapse imaging of this response shows that the aggregation occurs in cells that subsequently die 30 – 60 minutes post-wounding, indicating that GFP-Nit1 aggregation is an early marker of cell death at wound sites. Time-lapse confocal imaging was used to characterize wound-induced cell death using GFP-Nit1 and markers of the nucleus and endoplasmic reticulum. These analyses provide dynamic portraits of well-known death-associated responses such as nuclear contraction and cellular collapse and reveal novel features such as nuclear envelope separation, ER vesiculation and loss of nuclear-lumen contents. As a parallel system for imaging cell death, we developed a chemical method for rapidly triggering cell death using the herbicides bromoxynil or chloroxynil which cause rapid GFP-Nit1 aggregation, loss of nuclear contents and cellular collapse, but not nuclear contraction, separating this response from others during plant cell death. Conclusion Our observations place aggregation of Nitrilase 1 as one of the earliest events associated with wound and herbicide-induced cell death and highlight several novel cellular events that occur as plant cells die. Our data create a detailed descriptive framework for future investigations of plant cell death and provide new tools for both its cellular and biochemical analysis. PMID

  19. Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Justin Chapman

    2010-11-01

    Full Text Available Insulin resistance is manifested in muscle, adipose tissue, and liver and is associated with adipose tissue inflammation. The cellular components and mechanisms that regulate the onset of diet-induced insulin resistance are not clearly defined.We initially observed osteopontin (OPN mRNA over-expression in adipose tissue of obese, insulin resistant humans and rats which was normalized by thiazolidinedione (TZD treatment in both species. OPN regulates inflammation and is implicated in pathogenic maladies resulting from chronic obesity. Thus, we tested the hypothesis that OPN is involved in the early development of insulin resistance using a 2-4 week high fat diet (HFD model. OPN KO mice fed HFD for 2 weeks were completely protected from the severe skeletal muscle, liver and adipose tissue insulin resistance that developed in wild type (WT controls, as determined by hyperinsulinemic euglycemic clamp and acute insulin-stimulation studies. Although two-week HFD did not alter body weight or plasma free fatty acids and cytokines in either strain, HFD-induced hyperleptinemia, increased adipose tissue inflammation (macrophages and cytokines, and adipocyte hypertrophy were significant in WT mice and blunted or absent in OPN KO mice. Adipose tissue OPN protein isoform expression was significantly altered in 2- and 4-week HFD-fed WT mice but total OPN protein was unchanged. OPN KO bone marrow stromal cells were more osteogenic and less adipogenic than WT cells in vitro. Interestingly, the two differentiation pathways were inversely affected by HFD in WT cells in vitro.The OPN KO phenotypes we report reflect protection from insulin resistance that is associated with changes in adipocyte biology and adipose tissue inflammatory status. OPN is a key component in the development of HFD-induced insulin resistance.

  20. White spot syndrome virus induces metabolic changes resembling the warburg effect in shrimp hemocytes in the early stage of infection.

    Science.gov (United States)

    Chen, I-Tung; Aoki, Takashi; Huang, Yun-Tzu; Hirono, Ikuo; Chen, Tsan-Chi; Huang, Jiun-Yan; Chang, Geen-Dong; Lo, Chu-Fang; Wang, Han-Ching

    2011-12-01

    The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection.

  1. Early TBI-induced cytokine alterations are similarly detected by two distinct methods of multiplex assay.

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    Sanjib eMukherjee

    2011-09-01

    Full Text Available Annually, more than a million persons experience traumatic brain injury (TBI in the US and a substantial proportion of this population develop debilitating neurological disorders, such as, paralysis, cognitive deficits and epilepsy. Despite the long-standing knowledge of the risks associated with TBI, no effective biomarkers or interventions exist. Recent evidence suggests a role for inflammatory modulators in TBI-induced neurological impairments. Current technological advances allow for the simultaneous analysis of the precise spatial and temporal expression patterns of numerous proteins in single samples which ultimately can lead to the development of novel treatments. Thus, the present study examined 23 different cytokines, including chemokines, in the ipsi and contralateral cerebral cortex of rats at 24 hours after a Fluid Percussion Injury (FPI. Furthermore, the estimation of cytokines were performed in a newly developed multiplex assay instrument, MAGPIX (Luminex Corp and compared with an established instrument, Bio-Plex (Bio-Rad, in order to validate the newly developed instrument. The results show numerous inflammatory changes in the ipsi and contralateral side after FPI that were consistently reported by both technologies.

  2. Edge transport and fluctuation induced turbulence characteristics in early SST-1 plasma

    Energy Technology Data Exchange (ETDEWEB)

    Kakati, B., E-mail: bharat.kakati@ipr.res.in; Pradhan, S., E-mail: pradhan@ipr.res.in; Dhongde, J.; Semwal, P.; Yohan, K.; Banaudha, M.

    2017-02-15

    Highlights: • Anomalous particle transport during the high MHD activity at SST-1. • Electrostatic turbulence is modulated by MHD activity at SST-1 tokamak. • Edge floating potential fluctuations shows poloidal long-range cross correlation. - Abstract: Plasma edge transport characteristics are known to be heavily influenced by the edge fluctuation induced turbulences. These characteristics play a critical role towards the confinement of plasma column in a Tokamak. The edge magnetic fluctuations and its subsequent effect on electrostatic fluctuations have been experimentally investigated for the first time at the edge of the SST-1 plasma column. This paper reports the correlations that exist and is experimentally been observed between the edge densities and floating potential fluctuations with the magnetic fluctuations. The edge density and floating potential fluctuations have been measured with the help of poloidally separated Langmuir probes, whereas the magnetic fluctuations have been measured with poloidally spaced Mirnov coils. Increase in magnetic fluctuations associated with enhanced MHD activities has been found to increase the floating potential and ion saturation current. These observations indicate electrostatic turbulence getting influenced with the MHD activities and reveal the edge anomalous particle transport during SST-1 tokamak discharge. Large-scale coherent structures have been observed in the floating potential fluctuations, indicating long-distance cross correlation in the poloidal directions. From bispectral analysis, a strong nonlinear coupling among the floating potential fluctuations is observed in the low-frequency range about 0–15 kHz.

  3. Induced spawning and early ontogeny in hatchery-reared catfish Zungaro jahu (Siluriformes: Pimelodidae

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    Lorena B. Nogueira

    Full Text Available Hatchery-kept catfish jahus Zungaro jahu (Ihering, 1898 were induced to spawn with carp pituitary extract. The telolecithal eggs were round (1.6 ± 0.1 mm in diameter, demersal, free, and covered with a 0.4 mm-thick jelly coat. The gonadosomatic index of 2.8 was comparable to that of other Pimelodidae. The number of eggs x g of ova-1 was 804 ± 144. Hatching occurred 14.5 h after fertilization, at a temperature of 27.3 ± 0.4º C. The newly-hatched embryos measured 3.9-4.3 mm of total length (TL. At 18 h post-hatching (HPH; 5.3 ± 0.1 mm TL, the retina was pigmented, the mouth opened and dorsoflexion of the notochord had initiated. At 36 HPH (6.4 ± 0.2 mm TL, fusiform chromatophores were vertically arranged in the primordial fin fold and the notochord was dorsoflexed. The yolk sac was almost exhausted by 48 HPH (7.3 ± 0.2 mm TL. At 128 HPH (8.6 ± 0.6 mm TL the pectoral, dorsal, adipose, caudal, anal, and pelvic fins were readily observable whereas the primordial fin fold was no longer visible. At 224 HPH (16.6 ± 2.5 mm TL, the metamorphosis was completed and the larvae had acquired the juvenile appearance.

  4. Amplification of oncogenes in early-stage, radiation-induced rat skin tumours

    International Nuclear Information System (INIS)

    Ashkenazi-Kimmel, T.

    1989-10-01

    The effect of gene amplification on tumour size and growth was investigated in 39 samples collected from 23 radiation-induced rat skin tumours. The relationships of both the time from irradiation and the time from first appearance of the tumour to gene amplification were also examined. DNA from each tumour sample was extracted and probed for abl, fos, c-myc, N-myc, H-ras, and K-ras, and amplification of all but N-myc was detected. A single amplified gene was observed in 8 of 39 samples; multiple amplified genes were found in an additional 7. The amplification of c-myc, H-ras, or K-ras was found to be associated with increase in tumour size. c-myc amplification was also associated with an increase in growth rate. Amplification of c-myc was found to occur as a late-stage event in these tumours. The results suggest that both myc and ras genes play unique roles in the growth and development of radiation tumours, and they provide new information on the temporal aspects of c-myc activation. 77 refs., 26 figs., 11 tabs

  5. No difference in emergence time and early cognitive function between sevoflurane-fentanyl and propofol-remifentanil in patients undergoing craniotomy for supratentorial intracranial surgery.

    Science.gov (United States)

    Magni, G; Baisi, F; La Rosa, I; Imperiale, C; Fabbrini, V; Pennacchiotti, M L; Rosa, G

    2005-07-01

    Balanced anesthesia with sevoflurane-fentanyl has been widely accepted as anesthetic management for neurosurgery. Propofol-remifentanil regimen has been successfully used in various surgical settings, but a comprehensive comparison of sevoflurane-fentanyl and propofol-remifentanil anesthesia in patients undergoing craniotomy for supratentorial intracranial surgery has not yet been done. The aim of this prospective, randomized, open-label clinical trial was to compare clinical properties of sevoflurane-fentanyl with propofol-remifentanil anesthesia in patients undergoing supratentorial intracranial surgery. The primary endpoint was to compare early postoperative recovery and cognitive functions within the two groups; we also evaluated hemodynamic events, vomiting, shivering, and pain. One hundred twenty patients (64 males; age 15-75 years) were randomized to either total intravenous anesthesia (group T) or sevoflurane anesthesia (group S). Emergence and extubation times and cognitive function (Short Orientation Memory Concentration Test [SOMCT]) were compared in the two groups. Brain swelling, incidence of hypotensive and hypertensive episodes, postoperative vomiting, shivering, and pain were also analyzed. The mean emergence time (12.2 +/- 4.9 minutes for group S versus 12.3 +/- 6.1 minutes for group T; P = 0.92) and extubation time (18.2 +/- 2.3 minutes for group S versus 18.3 +/- 2.1 minutes for group T; P = 0.80) were similar in the two groups. Average SOMCT scores, both 15 minutes after extubation (25.6 +/- 4.9 in group S versus 23.9 +/- 7.5 in group T; P = 0.14) and 45 minutes after extubation (27.3 +/- 2.2 in group S versus 26.0 +/- 5.1 in group T; P = 0.07) were also comparable. Brain swelling was present in seven and five patients in groups S and T, respectively (P = 0.76). Hypotension was present in 12% (group S) and 28% (group T) of patients (P = 0.02). Hypertension was present in 17% of patients in group S and 40% of patients in group T (P = 0

  6. Early activation of wheat polyamine biosynthesis during Fusarium head blight implicates putrescine as an inducer of trichothecene mycotoxin production

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    Rusu Anca

    2010-12-01

    Full Text Available Abstract Background The fungal pathogen Fusarium graminearum causes Fusarium Head Blight (FHB disease on wheat which can lead to trichothecene mycotoxin (e.g. deoxynivalenol, DON contamination of grain, harmful to mammalian health. DON is produced at low levels under standard culture conditions when compared to plant infection but specific polyamines (e.g. putrescine and agmatine and amino acids (e.g. arginine and ornithine are potent inducers of DON by F. graminearum in axenic culture. Currently, host factors that promote mycotoxin synthesis during FHB are unknown, but plant derived polyamines could contribute to DON induction in infected heads. However, the temporal and spatial accumulation of polyamines and amino acids in relation to that of DON has not been studied. Results Following inoculation of susceptible wheat heads by F. graminearum, DON accumulation was detected at two days after inoculation. The accumulation of putrescine was detected as early as one day following inoculation while arginine and cadaverine were also produced at three and four days post-inoculation. Transcripts of ornithine decarboxylase (ODC and arginine decarboxylase (ADC, two key biosynthetic enzymes for putrescine biosynthesis, were also strongly induced in heads at two days after inoculation. These results indicated that elicitation of the polyamine biosynthetic pathway is an early response to FHB. Transcripts for genes encoding enzymes acting upstream in the polyamine biosynthetic pathway as well as those of ODC and ADC, and putrescine levels were also induced in the rachis, a flower organ supporting DON production and an important route for pathogen colonisation during FHB. A survey of 24 wheat genotypes with varying responses to FHB showed putrescine induction is a general response to inoculation and no correlation was observed between the accumulation of putrescine and infection or DON accumulation. Conclusions The activation of the polyamine biosynthetic

  7. Early activation of wheat polyamine biosynthesis during Fusarium head blight implicates putrescine as an inducer of trichothecene mycotoxin production.

    Science.gov (United States)

    Gardiner, Donald M; Kazan, Kemal; Praud, Sebastien; Torney, Francois J; Rusu, Anca; Manners, John M

    2010-12-30

    The fungal pathogen Fusarium graminearum causes Fusarium Head Blight (FHB) disease on wheat which can lead to trichothecene mycotoxin (e.g. deoxynivalenol, DON) contamination of grain, harmful to mammalian health. DON is produced at low levels under standard culture conditions when compared to plant infection but specific polyamines (e.g. putrescine and agmatine) and amino acids (e.g. arginine and ornithine) are potent inducers of DON by F. graminearum in axenic culture. Currently, host factors that promote mycotoxin synthesis during FHB are unknown, but plant derived polyamines could contribute to DON induction in infected heads. However, the temporal and spatial accumulation of polyamines and amino acids in relation to that of DON has not been studied. Following inoculation of susceptible wheat heads by F. graminearum, DON accumulation was detected at two days after inoculation. The accumulation of putrescine was detected as early as one day following inoculation while arginine and cadaverine were also produced at three and four days post-inoculation. Transcripts of ornithine decarboxylase (ODC) and arginine decarboxylase (ADC), two key biosynthetic enzymes for putrescine biosynthesis, were also strongly induced in heads at two days after inoculation. These results indicated that elicitation of the polyamine biosynthetic pathway is an early response to FHB. Transcripts for genes encoding enzymes acting upstream in the polyamine biosynthetic pathway as well as those of ODC and ADC, and putrescine levels were also induced in the rachis, a flower organ supporting DON production and an important route for pathogen colonisation during FHB. A survey of 24 wheat genotypes with varying responses to FHB showed putrescine induction is a general response to inoculation and no correlation was observed between the accumulation of putrescine and infection or DON accumulation. The activation of the polyamine biosynthetic pathway and putrescine in infected heads prior to

  8. Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.

    Science.gov (United States)

    Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz

    2015-06-01

    There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus. © The Author(s) 2015.

  9. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Gao, Xiugong; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-01-01

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds

  10. Identification of early biomarkers during acetaminophen-induced hepatotoxicity by fourier transform infrared microspectroscopy.

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    Rekha Gautam

    Full Text Available Acetaminophen is a widely prescribed drug used to relieve pain and fever; however, it is a leading cause of drug-induced liver injury and a burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing of acetaminophen was investigated using liver and sera samples with Fourier Transform Infrared microspectroscopy. The infrared spectra of acetaminophen treated livers in BALB/c mice show decrease in glycogen, increase in amounts of cholesteryl esters and DNA respectively. Rescue experiments using L-methionine demonstrate that depletion in glycogen and increase in DNA are abrogated with pre-treatment, but not post-treatment, with L-methionine. This indicates that changes in glycogen and DNA are more sensitive to the rapid depletion of glutathione. Importantly, analysis of sera identified lowering of glycogen and increase in DNA and chlolesteryl esters earlier than increase in alanine aminotransferase, which is routinely used to diagnose liver damage. In addition, these changes are also observed in C57BL/6 and Nos2(-/- mice. There is no difference in the kinetics of expression of these three molecules in both strains of mice, the extent of damage is similar and corroborated with ALT and histological analysis. Quantification of cytokines in sera showed increase upon APAP treatment. Although the levels of Tnfα and Ifnγ in sera are not significantly affected, Nos2(-/- mice display lower Il6 but higher Il10 levels during this acute model of hepatotoxicity. Overall, this study reinforces the growing potential of Fourier Transform Infrared microspectroscopy as a fast, highly sensitive and label-free technique for non-invasive diagnosis of liver damage. The combination of Fourier Transform Infrared microspectroscopy and cytokine analysis is a powerful tool to identify multiple biomarkers, understand differential host responses and evaluate therapeutic regimens during liver damage and, possibly, other diseases.

  11. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-08-15

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.

  12. Effect of early treatment with transcutaneous electrical diaphragmatic stimulation (TEDS on pulmonary inflammation induced by bleomycin

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    Laisa A. Santos

    2013-12-01

    Full Text Available BACKGROUND : Bleomycin (B is an antineoplastic drug that has pulmonary fibrosis as a side effect. There are few experimental studies about the effects of physical therapy treatment in this case. OBJECTIVE: The objective was to study rat lungs treated with B and precocious intervention by transcutaneous electrical diaphragmatic stimulation (TEDS. METHOD : Wistar rats were divided into 4 groups (n=5: a control group (C; a stimulated group (TEDS; a group treated with a single dose of B (intratracheally, 2.5 mg/kg (B; and a group treated with B and electric stimulation (B + TEDS. After the B instillation, the electrical stimulation was applied for 7 days, for a duration of 20 minutes. Lung fragments were histologically processed with hematoxylin and eosin (HE and 8-isoprostane-PGF2α (8-iso-PGF2α. The density of the alveolar area was determined by planimetry, the inflammatory profile was defined by the number of cells, and the level of oxidative stress in the pulmonary tissue was evaluated by 8-iso-PGF2α. For statistical analysis of the data, the Shapiro-Wilk test was used, followed by a one-way ANOVA with the post-hoc Bonferroni test (p≤0.05. RESULTS : The B group exhibited a significant reduction in the area density, and the acute treatment with B + TEDS prevented this reduction. There were increased numbers of fibroblasts, leukocytes, and macrophages in the B group, as well as increased lipid peroxidation, which was observed only in this group. CONCLUSION : B promoted a reduction in the alveolar density area, thereby inducing the inflammatory process and increasing the production of free radicals. These effects were minimized by the application of TEDS at the initial treatment stage.

  13. NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout

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    Carlos Henríquez-Olguín

    2016-07-01

    Full Text Available Reactive oxygen species (ROS participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2 in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB. Moreover, exercise significantly increased NOX2 complex assembly (p47phox-gp91phox interaction demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD, glutathione peroxidase (GPx, citrate synthase (CS, mitochondrial transcription factor A (tfam and interleukin-6 (IL-6 in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p<0.001. These results were corroborated using gp91-dstat in an in-vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

  14. Trastuzumab interruption and treatment-induced cardiotoxicity in early HER2-positive breast cancer

    Science.gov (United States)

    Yu, Anthony F.; Yadav, Nandini U.; Lung, Betty Y.; Eaton, Anne A.; Thaler, Howard T.; Hudis, Clifford A.; Dang, Chau T.; Steingart, Richard M.

    2016-01-01

    Trastuzumab improves outcomes among patients with HER2-positive breast cancer but is associated with a risk of treatment-induced cardiotoxicity (TIC). It is unclear how frequently TIC leads to trastuzumab interruption outside of prospective trials, and how TIC is managed in clinical practice. Patients with HER2-postive breast cancer receiving adjuvant trastuzumab from 2005 to 2010 were identified (n = 608). We evaluated the incidence, risk factors, and management of trastuzumab interruption due to TIC. In total, 488 (80 %) patients were treated with anthracycline prior to trastuzumab. Trastuzumab was interrupted in 108 (18 %) patients. Cumulative trastuzumab dose was lower in the interrupted group (median 86 vs. 108 mg/kg, p<0.0001). The most common reason for interruption was TIC (66 of 108 patients): 20 had symptomatic heart failure and 46 had asymptomatic left ventricular ejection fraction (LVEF) decline. Patients with trastuzumab interruption for TIC were older (54 vs. 50 years, p = 0.014) with lower LVEF before anthracycline (63 vs. 67 %, p<0.0001) and trastuzumab (62 vs. 67 %, p<0.0001) therapy. Mean LVEF at baseline, TIC diagnosis, and follow-up after trastuzumab interruption was 63, 45, and 55 %, respectively. Thirty-three of 66 patients with TIC were re-challenged with trastuzumab, and five patients had recurrent LVEF decline. In clinical practice, trastuzumab interruption is common and most often due to TIC, with most patients receiving anthracycline prior to trastuzumab. Cardiac dysfunction improves after trastuzumab interruption but may not fully recover to baseline. Strategies to minimize cardiotoxicity and treatment interruption should be investigated to prevent persistent left ventricular dysfunction in affected patients. PMID:25552363

  15. Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control.

    Directory of Open Access Journals (Sweden)

    Christina Bächle

    Full Text Available This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control.In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9 for symptoms of depression and severity of depressive symptoms (PHQ-9 score. Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c.A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation was 5.3 (4.4 among women and 3.9 (3.6 among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (βwomen 3.8, p<0.001. However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (βmen 0.14, p=0.006.Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes.

  16. Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control.

    Science.gov (United States)

    Bächle, Christina; Lange, Karin; Stahl-Pehe, Anna; Castillo, Katty; Scheuing, Nicole; Holl, Reinhard W; Giani, Guido; Rosenbauer, Joachim

    2015-01-01

    This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control. In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9) for symptoms of depression and severity of depressive symptoms (PHQ-9 score). Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c. A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation) was 5.3 (4.4) among women and 3.9 (3.6) among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (βwomen 3.8, peating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (βmen 0.14, p=0.006). Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes.

  17. EGS in sedimentary basins: sensitivity of early-flowback tracer signals to induced-fracture parameters