WorldWideScience

Sample records for late cns risks

  1. Oral Session 03: CNS Risk

    International Nuclear Information System (INIS)

    Narici, Livio; Nelson, Gregory A.

    2014-01-01

    Exposure to space radiation may have impacts on brain function, either during or following missions. It is most important to determine how low doses of protons and high-LET irradiation elicit changes in brain function. Within this framework, the role of oxidative stress should also be assessed, as well as other possible interaction mechanisms involving, e.g., genetic, environmental, and sex-dependent risk factors. The hippocampus is particularly susceptible to radiation. It plays an essential role in memory formation and consolidation and is one of the most investigated brain components for its responses to radiation. The hippocampus is also one of the first brain structures to be damaged in the pathogenesis of Alzheimer's disease, an important potential late impairment following irradiation. In ‘Section 3: CNS risk’, six papers have been presented focused on these issues. For details the reader is directed to the specific papers. Here a very short summary follows

  2. Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

    Science.gov (United States)

    Cucinotta, Francis A.; Ponomarev, Artem

    2009-01-01

    A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

  3. Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

    International Nuclear Information System (INIS)

    Trigg, M.E.; Makuch, R.; Glaubiger, D.

    1985-01-01

    Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

  4. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    Science.gov (United States)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  5. Risk management and post-marketing surveillance of CNS drugs.

    Science.gov (United States)

    Henningfield, Jack E; Schuster, Charles R

    2009-12-01

    Drugs affecting the central nervous system span a broad range of chemical entities, dosage forms, indications, and risks. Unintended consequences include potential abuse and overdose in non-patient drug abusers, deliberate tampering of drug dosage forms, and criminal behavior associated with diversion. Regulators must consider diverse factors to find the appropriate conditions of approval to minimize unintended consequences while enabling a level of access desired by health care providers and patients. This commentary appears as part of a special issue of Drug and Alcohol Dependence that focuses on risk management and post-marketing surveillance and addresses key issues that pose real-world challenges to pharmaceutical sponsors and regulators in particular. For example, in the U.S., Controlled Substances Act drug scheduling can be considered a risk management strategy but its legal authorities and administrative processes are independent from those of risk management (including Risk Evaluation and Mitigation Strategies or REMS); better harmonization of these approaches is vital from drug development and regulatory perspectives. Risk management would ideally be implemented on a strong science foundation demonstrating that the tools employed to mitigate risks and ensure safe use are effective. In reality, research and evaluation of tools in this area is in its infancy and will necessarily be an evolutionary process; furthermore, there is little precedent for linking interventions and program evolution to unintended consequences such as regional outbreaks of abuse and diversion. How such issues are resolved has the potential to stimulate or stifle innovations in drug development and advance or imperil health care.

  6. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Directory of Open Access Journals (Sweden)

    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  7. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Science.gov (United States)

    Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

    2014-12-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  8. Commercial viability of CNS drugs: balancing the risk/reward profile.

    Science.gov (United States)

    Johnson, Ginger S

    2014-01-01

    CNS has historically been a formidable therapeutic area in which to innovate owing to biological (e.g., complex neurobiology, difficulty reaching the target), as well as clinical (e.g., subjective clinical endpoints, high placebo response, lack of biomarkers) challenges. In the current market where many of the larger diseases are dominated by a generic standard of care, commercial challenges now make the triple threat of scientific-clinical-commercial risk too much for many players to tackle. However, opportunities do exist for smaller biotech companies to concentrate on narrowly focused patient populations associated with high unmet need for which risk can be tightly defined. In CNS, there are two major areas to balance the risk/reward profile and create commercially viable opportunities: To realize value, all companies (start-ups and big players) must define, measure and quantify clear and meaningful value to all stakeholders: physicians, patients, caregivers and payers. © 2013.

  9. Decreased Cognitive/CNS Function in Young Adults at Risk for Hypertension: Effects of Sleep Deprivation

    Directory of Open Access Journals (Sweden)

    James A. McCubbin

    2012-01-01

    Full Text Available Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed.

  10. Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection

    OpenAIRE

    Campbell, Jennifer H.; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J.; Tse, Samantha; Miller, Andrew D.; González, R. Gilberto; Salemi, Marco; Burdo, Tricia H.; Williams, Kenneth C.

    2014-01-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages a...

  11. LATE-BREAKING ABSTRACT: Early relapse of non-small cell lung cancer (NSCLC) found after CNS-symptoms

    DEFF Research Database (Denmark)

    Hansen, Niels-Chr. G.; Laursen, Christian B.; Jeppesen, Stefan S.

    2016-01-01

    whether the introduction in 2010 of follow-up by CT of thorax and upper abdomen every three months has reduced the incidence of relapse suspected from CNS-symptoms.Results: All 827 NSCLC patients from Funen completing curative treatment from 2005 to 2013 were included. The total number of relapses found...... or III were found.Conclusion: CT-based follow-up has not reduced the incidence of relapse suspected from CNS-symptoms in stage II-IV, and therefore we suggest routine MR of the brain before curative treatment for this group of patients.Number, fractions(%), and [95%CI]Jan. 2005 - June 2010July 2010 - Dec...... after symptoms within 24 months decreased in the 3½ years after the introduction of CT-based follow-up, p < 0,001 (table), but the total fraction presenting with CNS-symptoms did not change, p = 0.296. Relapses after stage I cancer decreased (p = 0.025), while no differences or changes for stages II...

  12. Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study

    NARCIS (Netherlands)

    Chellapandian, Deepak; Shaikh, Furqan; van den Bos, Cor; Somers, Gino R.; Astigarraga, Itziar; Jubran, Rima; Degar, Barbara; Carret, Anne-Sophie; Mandel, Karen; Belletrutti, Mark; Dix, David; Visser, Johannes; Abuhadra, Nour; Chang, Tiffany; Rollins, Barret; Whitlock, James; Weitzman, Sheila; Abla, Oussama

    2015-01-01

    Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or

  13. Space Radiation Cancer, Circulatory Disease and CNS Risks for Near Earth Asteroid and Mars Missions: Uncertainty Estimates for Never-Smokers

    Science.gov (United States)

    Cucinotta, Francis A.; Chappell, Lori J.; Wang, Minli; Kim, Myung-Hee

    2011-01-01

    The uncertainties in estimating the health risks from galactic cosmic rays (GCR) and solar particle events (SPE) are a major limitation to the length of space missions and the evaluation of potential risk mitigation approaches. NASA limits astronaut exposures to a 3% risk of exposure induced cancer death (REID), and protects against uncertainties in risks projections using an assessment of 95% confidence intervals after propagating the error from all model factors (environment and organ exposure, risk coefficients, dose-rate modifiers, and quality factors). Because there are potentially significant late mortality risks from diseases of the circulatory system and central nervous system (CNS) which are less well defined than cancer risks, the cancer REID limit is not necessarily conservative. In this report, we discuss estimates of lifetime risks from space radiation and new estimates of model uncertainties are described. The key updates to the NASA risk projection model are: 1) Revised values for low LET risk coefficients for tissue specific cancer incidence, with incidence rates transported to an average U.S. population to estimate the probability of Risk of Exposure Induced Cancer (REIC) and REID. 2) An analysis of smoking attributable cancer risks for never-smokers that shows significantly reduced lung cancer risk as well as overall cancer risks from radiation compared to risk estimated for the average U.S. population. 3) Derivation of track structure based quality functions depends on particle fluence, charge number, Z and kinetic energy, E. 4) The assignment of a smaller maximum in quality function for leukemia than for solid cancers. 5) The use of the ICRP tissue weights is shown to over-estimate cancer risks from SPEs by a factor of 2 or more. Summing cancer risks for each tissue is recommended as a more accurate approach to estimate SPE cancer risks. 6) Additional considerations on circulatory and CNS disease risks. Our analysis shows that an individual s

  14. CNS role evolution.

    Science.gov (United States)

    Payne, J L; Baumgartner, R G

    1996-01-01

    THE CNS ROLE has been actualized in a variety of ways. Flexibility-inherent in the role-and the revolution in health care consciousness tend to place the CNS at risk for criticism regarding value to the organization. At Vanderbilt University Medical Center, a CNS task force evaluated the current reality of CNS practice and recommended role changes to include the financial analysis of patient care. After incorporating a financial perspective into our present practice, we have embarked on an interesting journey of post-Master's degree study, that of the tertiary care nurse practitioner. This practice option could elevated the clinical and financial aspects of providing cost-effective health care to a more autonomous role form; however, the transition has been challenging. Since 1990, the American Nurses Association has recommended that nursing school curricula change to meet the needs of the health care environment and provide increased career flexibility through creating one advanced degree incorporating both CNS and NP functions. Swiftly moving past differences and toward similarities will bridge the gap for advanced practice nurses in the future.

  15. Dose-dense chemoimmunotherapy and CNS prophylaxis in patients with high-risk DLBCL: a comparison of Nordic CRY-04 and CHIC studies

    DEFF Research Database (Denmark)

    Leppä, Sirpa; Jørgensen, Judit Meszaros; Brown, Peter De Nully

    Background: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression relatively high. We investigated the efficacy of dose-dense chemoimmunotherapy and systemic CNS prophylaxis in two completed Nordic trials...... including patients less than 65 years with high-risk DLBCL. We combined individual patient data from these studies to compare clinical outcome and prognostic factors in patients treated with CNS prophylaxis given in the beginning (CHIC) vs at the end (CRY-04) of therapy. Patients and methods: Inclusion...... proliferation index (Ki67 expression available PET data, Deauville score 5 at the end of treatment was associated with increased rate of progression and death in both trials (p=0.012). Only one out of 17 biopsies from PET positive...

  16. Sleep disorders in children after treatment for a CNS tumour.

    Science.gov (United States)

    Verberne, Lisa M; Maurice-Stam, Heleen; Grootenhuis, Martha A; Van Santen, Hanneke M; Schouten-Van Meeteren, Antoinette Y N

    2012-08-01

    The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8±2.8 versus 7.5±2.7; Psleep. No specific risk factors were identified for a sleep disorder in CNS tumour patients, but their excessive somnolence was correlated with lower fatigue related quality of life (QoL) (r=-0.78, Psleep quality and diminish fatigue. © 2011 European Sleep Research Society.

  17. The transition from day-to-night activity is a risk factor for the development of CNS oxygen toxicity in the diurnal fat sand rat (Psammomys obesus).

    Science.gov (United States)

    Eynan, Mirit; Biram, Adi; Mullokandov, Michael; Kronfeld-Schor, Noga; Paz-Cohen, Rotem; Menajem, Dvir; Arieli, Yehuda

    2017-01-01

    Performance and safety are impaired in employees engaged in shift work. Combat divers who use closed-circuit oxygen diving apparatus undergo part of their training during the night hours. The greatest risk involved in diving with such apparatus is the development of central nervous system oxygen toxicity (CNS-OT). We investigated whether the switch from day-to-night activity may be a risk factor for the development of CNS-OT using a diurnal animal model, the fat sand rat (Psammomys obesus). Animals were kept on a 12:12 light-dark schedule (6 a.m. to 6 p.m. at 500 lx). The study included two groups: (1) Control group: animals were kept awake and active during the day, between 09:00 and 15:00. (2) Experimental group: animals were kept awake and active during the night, between 21:00 and 03:00, when they were exposed to dim light in order to simulate the conditions prevalent during combat diver training. This continued for a period of 3 weeks, 5 days a week. On completion of this phase, 6-sulphatoxymelatonin (6-SMT) levels in urine were determined over a period of 24 h. Animals were then exposed to hyperbaric oxygen (HBO). To investigate the effect of acute melatonin administration, melatonin (50 mg/kg) or its vehicle was administered to the animals in both groups 20 min prior to HBO exposure. After the exposure, the activity of superoxide dismutase, catalase and glutathione peroxidase was measured, as were the levels of neuronal nitric oxide synthase (nNOS) and overall nitrotyrosylation in the cortex and hippocampus. Latency to CNS-OT was significantly reduced after the transition from day-to-night activity. This was associated with alterations in the level of melatonin metabolites secreted in the urine. Acute melatonin administration had no effect on latency to CNS-OT in either of the groups. Nevertheless, the activity of superoxide dismutase and catalase, as well as nitrotyrosine and nNOS levels, were altered in the hippocampus following melatonin

  18. Daytime activity and risk factors for late-life insomnia.

    Science.gov (United States)

    Morgan, Kevin

    2003-09-01

    Laboratory evidence linking exercise with improved sleep quality raises the possibility that the lower levels of physical activity characteristic of older age groups may contribute to late-life insomnia. While support for this hypothesis appears to come from epidemiological surveys, few such studies have distinguished satisfactorily between social and physical activities which differ widely in terms of energy cost and theoretical significance. The present analyses were, therefore, designed to assess the independent influence of physical and social activity levels on the prevalence and natural history of late-life insomnia. Survivors from a nationally representative UK sample (n = 1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n = 690) and 1993 (n = 410). Detailed assessments of physical and social activities, mental and physical health status, and sleep quality were made at each survey wave. Logistic regression models, adjusted for age, sex and health status, were used to assess relationships between activity levels and the prevalence, remission/persistence, and incidence of late-life insomnia. Lower physical health, depressed mood and lower physical (but not social) activity levels consistently emerged as significant risk factors for prevalent, persistent and incident insomnia. Age was unrelated to insomnia variables in all the cross-sectional models, but did emerge as a significant risk for cumulative 4-8-year insomnia incidence. These findings suggest that, independent of those activities more closely associated with social engagement, higher levels of customary physical activity per se appear to be protective against incident and chronic late-life insomnia.

  19. Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup Phase III BIG 02-98 Trial

    DEFF Research Database (Denmark)

    Pestalozzi, B.C.; Francis, P.; Quinaux, E.

    2008-01-01

    BACKGROUND: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. PATIENTS AND METHODS: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG...

  20. 2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

    Science.gov (United States)

    2014-01-01

    The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

  1. What predictors matter: Risk factors for late adolescent outcomes.

    Science.gov (United States)

    Wall-Wieler, Elizabeth; Roos, Leslie L; Chateau, Dan G; Rosella, Laura C

    2016-06-27

    A life course approach and linked Manitoba data from birth to age 18 were used to facilitate comparisons of two important outcomes: high school graduation and Attention-Deficit/Hyperactivity Disorder (ADHD). With a common set of variables, we sought to answer the following questions: Do the measures predicting high school graduation differ from those that predict ADHD? Which factors are most important? How well do the models fit each outcome? Administrative data from the Population Health Research Data Repository at the Manitoba Centre for Health Policy were used to conduct one of the strongest observational designs: multilevel modelling of large population (n = 62,739) and sibling (n = 29,444) samples. Variables included are neighbourhood characteristics, measures of family stability, and mental and physical health conditions in childhood and adolescence. The adverse childhood experiences important for each outcome differ. While family instability and economic adversity more strongly affect failing to graduate from high school, adverse health events in childhood and early adolescence have a greater effect on late adolescent ADHD. The variables included in the model provided excellent accuracy and discrimination. These results offer insights on the role of several family and social variables and can serve as the basis for reliable, valid prediction tools that can identify high-risk individuals. Applying such a tool at the population level would provide insight into the future burden of these outcomes in an entire region or nation and further quantify the burden of risk in the population.

  2. Prospective risk factors for alcohol misuse in late adolescence.

    Science.gov (United States)

    Ellickson, S L; Tucker, J S; Klein, D J; McGuigan, K A

    2001-11-01

    This longitudinal study investigated Grade-7 and Grade-10 risk factors for alcohol misuse at Grade 12. Alcohol misuse was conceptualized as problem-related drinking (e.g., missing school), high-risk drinking (e.g., drunk driving) and high consumption. Prospective analyses using two-part models predicted any alcohol misuse and the amount of misuse (given that some has occurred) for over 4,200 (52% male) participants in the RAND Adolescent Panel Study. Predictor variables were demographics, substance use and exposure, prodrug attitudes, rebelliousness and deviant behavior, self-esteem, family structure and relations, and grades. Grade-7 predictors of alcohol misuse 5 years later included early drinking onset, parental drinking, future intentions to drink, cigarette offers, difficulty resisting pressures to smoke, being white, being male, having an older sibling, deviant behavior and poor grades. By Grade 10, predictors of alcohol misuse 2 years later included drinking and marijuana use by self and peers, future intentions to drink, difficulty resisting pressures to drink and use marijuana, being male, coming from a disrupted family and deviant behavior. Somewhat different predictors were identified for problem-related, high-risk and high consumption drinking, emphasizing the importance of investigating multiple dimensions of misuse. The high social acceptability of alcohol use makes prevention difficult. Curbing alcohol misuse may be a more attainable goal than preventing any use. These results indicate that predictors of misuse in late adolescence can be identified by Grade 7 and are generally visible and modifiable. Prevention efforts should begin by early adolescence, address both familial and peer influences to drink and use other substances, and take into account problems that predict alcohol misuse (e.g., poor academic performance and early deviant behavior).

  3. CNS embryonal tumours: WHO 2016 and beyond.

    Science.gov (United States)

    Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

    2018-02-01

    Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

  4. Late-life depression is associated with an increased risk of multimorbidity and polypharmacy.

    NARCIS (Netherlands)

    Holvast, F.; Hattem, B. van; Verhaak, P.

    2016-01-01

    Background & Aim: late-life depression often coincides with chronic somatic diseases and, consequently, with polypharmacy. This may complicate medical treatment of older depressed patients. We aimed to determine the risk on multimorbidity and polypharmacy among older depressed primary care

  5. Comorbidities and the Risk of Late-Stage Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Steven T. Fleming

    2006-01-01

    Full Text Available The degree to which comorbidities affect the diagnosis of prostate cancer is not clear. The purpose of this study was to determine how comorbidities affect the stage at which prostate cancer is diagnosed in elderly white and black men. We obtained data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute merged with Medicare claims data. For each patient, we estimated associations between stage of disease at diagnosis and each of the 27 comorbidities. The sample included 2,489 black and 2,587 white men with staged prostate cancer. Coronary artery disease, benign hypertension, and dyslipidemia reduced the odds of late-stage prostate cancer. A prior diagnosis of peripheral vascular disease, severe renal disease, or substance abuse increased the odds of being diagnosed with late-stage disease. The study shows some effect modification by race, particularly among white men with substance abuse, cardiac conduction disorders, and other neurologic conditions. The strongest predictors of late-stage prostate cancer diagnosis for both white and black men were age at diagnosis of at least 80 years and lack of PSA screening. Comorbidities do affect stage at diagnosis, although in different ways. Four hypotheses are discussed to explain these findings.

  6. Early and Late Recurrent Epistaxis Admissions: Patterns of Incidence and Risk Factors.

    Science.gov (United States)

    Cohen, Oded; Shoffel-Havakuk, Hagit; Warman, Meir; Tzelnick, Sharon; Haimovich, Yaara; Kohlberg, Gavriel D; Halperin, Doron; Lahav, Yonatan

    2017-09-01

    Objective Epistaxis is a common complaint, yet few studies have focused on the incidence and risk factors of recurrent epistaxis. Our objective was to determine the patterns of incidence and risk factors for recurrent epistaxis admission (REA). Study Design Case series with chart review. Settings Single academic center. Subjects and Methods The medical records of patients admitted for epistaxis between 1999 and 2015 were reviewed. The follow-up period was defined as 3 years following initial admission. REAs were categorized as early (30 days) and late (31 days to 3 years) following initial admission. Logistic regression was used to identify potential predictors of REAs. Results A total of 653 patients were included. Eighty-six patients (14%) had REAs: 48 (7.5%) early and 38 (6.5%) late. Nonlinear incidence curve was demonstrated for both early and late REAs. Based on logistic regression, prior nasal surgery and anemia were independent risk factors for early REAs. According to multivariate analysis, thrombocytopenia was significantly associated with late REAs. Conclusion Early and late REAs demonstrate different risk predictors. Knowledge of such risk factors may help in risk stratification for this selected group of patients. All patients at risk should be advised on possible preventive measures. Patients at risk for early REA may benefit from a more proactive approach.

  7. Childhood cardiovascular risk factors, a predictor of late adolescent overweight

    Directory of Open Access Journals (Sweden)

    Saeed Kalantari

    2016-01-01

    Conclusion: Increased CVD risk factors are predictors of future overweight in childhood and adolescent and increased weight is linked significantly with dyslipidemia and hypertension in this age group.

  8. Supratentorial CNS malformations

    International Nuclear Information System (INIS)

    Zlatareva, D.

    2012-01-01

    Full text: Clinical suspicion of a developmental anomaly of the central nervous system (CNS) is a frequent indication for performing and magnetic resonance imaging (MRI) examination of the brain. Classification systems for malformation of the CNS are constantly revised according to newer scientific research. Developmental abnormalities can be classified in two main types. The first category consists of disorders of organogenesis in which genetic defects or any ischemic, metabolic, toxic or infectious insult to the developing brain can cause malformation. These malformations result from abnormal neuronal and glial proliferation and from anomalies of neuronal migration and or cortical organization. They are divided into supra- and infratentorial and may involve grey or white matter or both. The second category of congenital brain abnormalities is disorders of histogenesis which result from abnormal cell differentiation with a relatively normal brain appearance. Supratentorial CNS malformations could be divided into anomalies in telencephalic commissure, holoprosencephalies and malformations in cortical development. There are three main telencephalic commissures: the anterior commissure, the hippocampal commissure and the corpus callosum. Their morphology (hypoplasia, hyperplasia, agenesis, dysgenesis, even atrophy) reflects the development of the brain. Their agenesis, complete or partial, is one of the most commonly observed features in the malformations of the brain and is a part of many syndromes. Malformations of cortical development (MCD) are heterogeneous group of disease which result from disruption of 3 main stages of cortical development. The common clinical presentation is refractory epilepsy and or developmental delay. The most common MCD are heterotopias, focal cortical dysplasia, polymicrogyria, schizencephaly, pachygyria and lizencephaly. The exact knowledge of the brain anatomy and embryology is mandatory to provide a better apprehension of the

  9. Management of CNS tumors

    International Nuclear Information System (INIS)

    Griem, M.L.

    1987-01-01

    The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

  10. Flavonoids and the CNS

    DEFF Research Database (Denmark)

    Jäger, Anna Katharina; Saaby, Lasse

    2011-01-01

    Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure....... Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic ß-glucocidase. The absorbed aglycone is then conjugated by methylation......, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...

  11. Maternal perception of fetal activity and late stillbirth risk: findings from the Auckland Stillbirth Study.

    Science.gov (United States)

    Stacey, Tomasina; Thompson, John M D; Mitchell, Edwin A; Ekeroma, Alec; Zuccollo, Jane; McCowan, Lesley M E

    2011-12-01

      Maternal perception of decreased fetal movements has been associated with adverse pregnancy outcomes, including stillbirth. Little is known about other aspects of perceived fetal activity. The objective of this study was to explore the relationship between maternal perception of fetal activity and late stillbirth (≥28 wk gestation) risk.   Participants were women with a singleton, late stillbirth without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two control women with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Detailed demographic and fetal movement data were collected by way of interview in the first few weeks after the stillbirth, or at the equivalent gestation for control women.   A total of 155/215 (72%) women who experienced a stillbirth and 310/429 (72%) control group women consented to participate in the study. Maternal perception of increased strength and frequency of fetal movements, fetal hiccups, and frequent vigorous fetal activity were all associated with a reduced risk of late stillbirth. In contrast, perception of decreased strength of fetal movement was associated with a more than twofold increased risk of late stillbirth (aOR: 2.37; 95% CI: 1.29-4.35). A single episode of vigorous fetal activity was associated with an almost sevenfold increase in late stillbirth risk (aOR: 6.81; 95% CI: 3.01-15.41) compared with no unusually vigorous activity.   Our study suggests that maternal perception of increasing fetal activity throughout the last 3 months of pregnancy is a sign of fetal well-being, whereas perception of reduced fetal movements is associated with increased risk of late stillbirth. © 2011, Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc.

  12. Rare neonatal diabetes insipidus and associated late risks: Case report

    Directory of Open Access Journals (Sweden)

    Rivas-Crespo Maximiliano

    2012-05-01

    Full Text Available Abstract Background Most cases of neonatal central diabetes insipidus are caused by an injury, which often results in other handicaps in the patient. The infant’s prognosis will be determined by his or her own early age and disability as well as by the physician’s skill. However, the rarity of this condition prevents the acquisition of personal experience dealing with it. Case Presentation A neonatal hemorrhagic stroke, caused by an aortic coarctation, caused right lower limb paresis, swallowing disability, and central diabetes insipidus in a term infant. The scant oral intake, as a consequence of his disability, caused progressive undernutrition which closed a vicious circle, delaying his development and his ability to overcome the swallowing handicap. On the other hand, nasal desmopressin absorption was blocked by several common colds, resulting in brain bleeding because of severe dehydration. This even greater brain damage hampered the improvement of swallowing, closing a second harmful circle. Moreover, a devastating central myelinolysis with quadriplegia, caused by an uncontrolled intravenous infusion, consummated a pernicious sequence, possibly unreported. Conclusions The child’s overall development advanced rapidly when his nutrition was improved by gastrostomy: This was a key effect of nutrition on his highly sensitive neurodevelopment. Besides, this case shows potential risks related to intranasal desmopressin treatment in young children.

  13. Isolated vasculitis of the CNS

    International Nuclear Information System (INIS)

    Block, F.; Reith, W.

    2000-01-01

    Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [de

  14. Precarity in late life: Understanding new forms of risk and insecurity.

    Science.gov (United States)

    Grenier, Amanda; Phillipson, Chris; Laliberte Rudman, Debbie; Hatzifilalithis, Stephanie; Kobayashi, Karen; Marier, Patrik

    2017-12-01

    Population aging and longevity in the context of declining social commitments, raises concerns about disadvantage and widening inequality in late life. This paper explores the concept of precarity as a means to understand new and sustained forms of risk and insecurity that affect late life. The article begins with a review of the definition and uses of precarity in a range of scholarly fields including social gerontology. It then draws on illustrations from three locations of experience including older women, aging with a disability, and the foreign-born, to outline how precarity renders visible the disadvantages carried into late life, and new insecurities that emerge at the moment of needing care in the context of austerity. The argument being put forward is that precarity can be used to illustrate how risks and insecurities, experienced over time, in longevity, and the context of austerity, can deepen disadvantage. This lens thus holds the potential to challenge individual interpretations of risk, and situate experiences of disadvantage in the economic and political context. We conclude that contemporary conditions of austerity and longevity intersect to produce and sustain risk and disadvantage into late life. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Late Preterm Birth, Maternal Depression, and Risk of Preschool Psychiatric Disorders

    Science.gov (United States)

    Rogers, Cynthia E.; Lenze, Shannon N.; Luby, Joan L.

    2013-01-01

    Objective: Preterm children are at greater risk for psychiatric disorders, including anxiety disorders and attention-deficit/hyperactivity disorder (ADHD), than their term-born peers. Prior research has focused primarily on children born at early gestational ages. Less is known about the rate of psychiatric disorders among late preterm or early…

  16. Late-Adolescent Delinquency: Risks and Resilience for Girls Differing in Risk at the Start of Adolescence

    Science.gov (United States)

    Stevens, Tia; Morash, Merry; Park, Suyeon

    2011-01-01

    Based on resilience and feminist criminological theories, several individual, family, and community characteristics were hypothesized to predict late-adolescent delinquency for girls varying in early-adolescent risk. Girls aged 12 and 13 were interviewed each year as part of the National Longitudinal Survey of Youth 1997. Predictors of…

  17. Flavonoids and the CNS

    Directory of Open Access Journals (Sweden)

    Anna K. Jäger

    2011-02-01

    Full Text Available Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucocidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABAA-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson’s patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood.

  18. Sleep disorders in children after treatment for a CNS tumour

    NARCIS (Netherlands)

    Verberne, Lisa M.; Maurice-Stam, Heleen; Grootenhuis, Martha A.; van Santen, Hanneke M.; Schouten-van Meeteren, Antoinette Y. N.

    2012-01-01

    The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with

  19. Neural network development in late adolescents during observation of risk-taking action.

    Directory of Open Access Journals (Sweden)

    Miyuki Tamura

    Full Text Available Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression and age among late adolescents (n = 25, from 18 years and 1 month to 22 years and 8 months. The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions during functional magnetic resonance imaging (fMRI. The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas, and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus. We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed.

  20. Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Tomita, Natsuo; Soga, Norihito; Ogura, Yuji

    2013-01-01

    The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student's t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student's t-test) was performed. The median follow-up time was 35 months. Late Grade 2-3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P=0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose-volume modeling to predict rectal complications after HT. (author)

  1. Risk Factors for Late Aortic Valve Dysfunction After the David V Valve-Sparing Root Replacement.

    Science.gov (United States)

    Esaki, Jiro; Leshnower, Bradley G; Binongo, Jose N; Lasanajak, Yi; McPherson, LaRonica; Guyton, Robert A; Chen, Edward P

    2017-11-01

    Valve-sparing root replacement (VSRR) is an established therapy for aortic root pathology. However, late aortic valve dysfunction requiring reoperation remains a primary concern of this procedure. This study examines risk factors for late aortic insufficiency (AI) and aortic stenosis (AS) after David V VSRR. A retrospective review from 2005 to 2015 at a US academic center identified 282 patients who underwent VSRR. Cox proportional hazards regression analysis was used to identify risk factors for late AI and AS after VSRR. The mean age was 46.4 years. Sixty-four patients (22.7%) had bicuspid valves, and 41 patients (14.5%) had Marfan syndrome. The incidence of reoperations was 27 (9.6%), and 42 cases (14.9%) presented with acute type A dissection. Operative mortality was 8 (2.8%). Seven-year survival was 90.9%. Seven-year cumulative incidence of reoperation, greater than 2+ AI and greater than moderate AS were 3.1%, 2.2%, and 0.8%, respectively. Multivariable analysis showed aortic root size 55 mm or larger (hazard ratio 3.44, 95% confidence interval: 1.27 to 9.29, p = 0.01) to be a risk factor for late AI whereas bicuspid valve (hazard ratio 16.07, 95% confidence interval: 3.12 to 82.68, p = 0.001) and cusp repair were found to be risk factors (hazard ratio 5.91, 95% confidence interval: 1.17 to 29.86, p = 0.03) for late AS. Valve-sparing root replacement can be performed with low operative risk and good overall long-term survival even in complex clinical settings. Durable valve function can be expected; however, aortic root size 55 cm or more, bicuspid valve anatomy, and cusp repair represent independent risk factors for late aortic valve dysfunction after these procedures. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  2. CNS infections in immunocompetent patients

    International Nuclear Information System (INIS)

    Hartmann, K.M.; Zimmer, A.; Reith, W.

    2008-01-01

    This article gives a review of the most frequent infective agents reasonable for CNS infections in immunocompetent patients as well as their localisation and imaging specifications. MRI scanning is the gold standard to detect inflammatory conditions in the CNS. Imaging can be normal or nonspecifically altered although the infection is culturally or bioptically proven. There are no pathognomonic, pathogen-specific imaging criteria. The localization and dimension of the inflammation depends on the infection pathway. (orig.) [de

  3. VIIP: Central Nervous System (CNS) Modeling

    Science.gov (United States)

    Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry

    2015-01-01

    Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

  4. Prevalence and risk factors for urinary incontinence in pregnant women during late third trimester

    OpenAIRE

    Aruna Nigam; Ayesha Ahmad; Diksha Gaur; Arifa A. Elahi; Swaraj Batra

    2016-01-01

    Background: Urinary incontinence (UI) is defined as any involuntary urinary leakage by the International continence society (ICS). The objective of this study was to analyze the prevalence and risk factors of urinary incontinence in pregnant women in late third trimester. Methods: A questionnaire based survey done on 400 pregnant women in third trimester beyond 34 weeks of gestation. A pretested, semi structured questionnaire was used to enquire about demographic and personal information r...

  5. Crop connectivity under climate change: future environmental and geographic risks of potato late blight in Scotland.

    Science.gov (United States)

    Skelsey, Peter; Cooke, David E L; Lynott, James S; Lees, Alison K

    2016-11-01

    The impact of climate change on dispersal processes is largely ignored in risk assessments for crop diseases, as inoculum is generally assumed to be ubiquitous and nonlimiting. We suggest that consideration of the impact of climate change on the connectivity of crops for inoculum transmission may provide additional explanatory and predictive power in disease risk assessments, leading to improved recommendations for agricultural adaptation to climate change. In this study, a crop-growth model was combined with aerobiological models and a newly developed infection risk model to provide a framework for quantifying the impact of future climates on the risk of disease occurrence and spread. The integrated model uses standard meteorological variables and can be easily adapted to various crop pathosystems characterized by airborne inoculum. In a case study, the framework was used with data defining the spatial distribution of potato crops in Scotland and spatially coherent, probabilistic climate change data to project the future connectivity of crop distributions for Phytophthora infestans (causal agent of potato late blight) inoculum and the subsequent risk of infection. Projections and control recommendations are provided for multiple combinations of potato cultivar and CO 2 emissions scenario, and temporal and spatial averaging schemes. Overall, we found that relative to current climatic conditions, the risk of late blight will increase in Scotland during the first half of the potato growing season and decrease during the second half. To guide adaptation strategies, we also investigated the potential impact of climate change-driven shifts in the cropping season. Advancing the start of the potato growing season by 1 month proved to be an effective strategy from both an agronomic and late blight management perspective. © 2016 John Wiley & Sons Ltd.

  6. Application of empowerment theory for CNS practice.

    Science.gov (United States)

    Carlson-Catalano, J M

    1993-11-01

    Power is necessary for the clinical nurse specialist (CNS) to successfully conduct objectives of practice in bureaucratic hospital settings. To obtain power, the CNS could use strategies of an empowerment theory to fully operationalize roles in hospitals. This article will discuss how the CNS may be empowered utilizing strategies in four empowering categories. In addition, the many benefits of empowering the CNS are reviewed.

  7. Innate Interferons Regulate CNS Inflammation

    DEFF Research Database (Denmark)

    Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently...... potential IFN-inducing receptor that signals through NF-kB. Receptor activator of NF-kB (RANK) belongs to the TNF-receptor superfamily and has been shown to induce IFN-beta in medullary thymic epithelial cells affecting autoimmune regulatory processes and osteoclast precursor cells in association to bone...

  8. Population risk factors for late-stage presentation of cervical cancer in sub-Saharan Africa.

    Science.gov (United States)

    Stewart, Tessa S; Moodley, Jennifer; Walter, Fiona M

    2018-04-01

    Cervical cancer is the most prevalent malignancy in sub-Saharan Africa (SSA) with many women only seeking professional help when they are experiencing symptoms, implying late-stage malignancy and higher mortality rates. This ecological study assesses population-level exposures of SSA women to the numerous risk factors for HPV infection and cervical cancer, against late-stage presentation of cervical cancer. A literature review revealed the relevant risk factors in SSA. Open-access databases were mined for variables closely representing each risk factor. A proxy for late-stage presentation was used (ratio of incidence-to-mortality, IMR), and gathered from IARC's GLOBOCAN 2012 database. Variables showing significant correlation to the IMR were used in stepwise multiple regression to quantify their effect on the IMR. Countries with high cervical cancer mortality rates relative to their incidence have an IMR nearer one, suggesting a larger proportion of late-stage presentation. Western Africa had the lowest median IMR (1.463), followed by Eastern Africa (IMR = 1.595) and Central Africa (IMR = 1.675), whereas Southern Africa had the highest median IMR (1.761). Variables selected for the final model explain 65.2% of changes seen in the IMR. Significant predictors of IMR were GDP (coefficient = 2.189 × 10 -6 , p = 0.064), HIV infection (-1.936 × 10 -3 , p = 0.095), not using a condom (-1.347 × 10 -3 , p = 0.013), high parity (-1.744 × 10 -2 , p = 0.008), and no formal education (-1.311 × 10 -3 , p < 0.001). Using an IMR enables identification of factors predicting late-stage cervical cancer in SSA including: GDP, HIV infection, not using a condom, high parity and no formal education. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Risk factors for depressive symptoms in adolescent pregnancy in a late-teen subsample.

    Science.gov (United States)

    Koleva, Hristina; Stuart, Scott

    2014-04-01

    Depression in adolescent pregnancy is common but underrecognized and can be associated with negative medical outcomes. This brief report examines the relationship between depressive symptoms and various demographic and obstetrical risk factors, as well as the use of antidepressants in pregnant adolescents of late teenage years. Data were derived from a relatively large sample (506 women) recruited from university-based and community mental health centers in Iowa. A cross-sectional analysis did not reveal significant statistical associations between the risk factors and depressive symptoms (Beck Depression Inventory). Antidepressant use was very low (3.7 %), and adolescents with higher depression scores were more likely to take medications. In conclusion, screening for depression in pregnant adolescents should be universal, regardless of demographic and obstetrical risk factors, and promptly addressed.

  10. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    International Nuclear Information System (INIS)

    Prior, Phillip; Devisetty, Kiran; Tarima, Sergey S.; Lawton, Colleen A.F.; Semenenko, Vladimir A.

    2012-01-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose–response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose–response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and ≥36 months did not reveal significant differences (p ≥ .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose–response data to estimate the complication risks for the individual patient.

  11. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Prior, Phillip; Devisetty, Kiran [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Tarima, Sergey S. [Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI (United States); Lawton, Colleen A.F. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Semenenko, Vladimir A., E-mail: vsemenenko@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-05-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose-response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose-response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and {>=}36 months did not reveal significant differences (p {>=} .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose-response data to estimate the complication risks for the individual patient.

  12. Genetic models for CNS inflammation

    DEFF Research Database (Denmark)

    Owens, T; Wekerle, H; Antel, J

    2001-01-01

    The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily on ...

  13. Basic Concepts of CNS Development.

    Science.gov (United States)

    Nowakowski, R. S.

    1987-01-01

    The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…

  14. CNS complications of rotavirus gastroenteritis

    International Nuclear Information System (INIS)

    Volosinova, D.

    2010-01-01

    Rotavirus infection may be accompanied by serious complications, e.g. disabilities central nervous system (CNS). Theory rotavirus penetration across the blood-brain barrier and subsequent rota-associated convulsions by the 2-year case-history of the patient. Rotavirosis minor gastrointestinal symptoms may lead to erroneous diagnosis. (author)

  15. Late-Onset Alzheimer's Disease Polygenic Risk Profile Score Predicts Hippocampal Function.

    Science.gov (United States)

    Xiao, Ena; Chen, Qiang; Goldman, Aaron L; Tan, Hao Yang; Healy, Kaitlin; Zoltick, Brad; Das, Saumitra; Kolachana, Bhaskar; Callicott, Joseph H; Dickinson, Dwight; Berman, Karen F; Weinberger, Daniel R; Mattay, Venkata S

    2017-11-01

    We explored the cumulative effect of several late-onset Alzheimer's disease (LOAD) risk loci using a polygenic risk profile score (RPS) approach on measures of hippocampal function, cognition, and brain morphometry. In a sample of 231 healthy control subjects (19-55 years of age), we used an RPS to study the effect of several LOAD risk loci reported in a recent meta-analysis on hippocampal function (determined by its engagement with blood oxygen level-dependent functional magnetic resonance imaging during episodic memory) and several cognitive metrics. We also studied effects on brain morphometry in an overlapping sample of 280 subjects. There was almost no significant association of LOAD-RPS with cognitive or morphometric measures. However, there was a significant negative relationship between LOAD-RPS and hippocampal function (familywise error [small volume correction-hippocampal region of interest] p risk score based on APOE haplotype, and for a combined LOAD-RPS + APOE haplotype risk profile score (p risk genes on hippocampal function even in healthy volunteers. The effect of LOAD-RPS on hippocampal function in the relative absence of any effect on cognitive and morphometric measures is consistent with the reported temporal characteristics of LOAD biomarkers with the earlier manifestation of synaptic dysfunction before morphometric and cognitive changes. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

  16. Are former late-preterm children at risk for child vulnerability and overprotection?

    Science.gov (United States)

    Samra, Haifa A; McGrath, Jacqueline M; Wey, Howard

    2010-09-01

    Parent perception of child vulnerability (PPCV) and parent overprotection (POP) are believed to have serious implications for age appropriate cognitive and psychosocial development in very low birth weight preterm children. With recent concerns about suboptimal developmental outcomes in late-preterm children, this study was aimed at examining the relationship between history of late-preterm birth (34-36 6/7 weeks gestation), and PPCV, POP, and healthcare utilization (HCU). This was a cross-sectional observational design. Study participants were mothers of 54 healthy singleton children recruited from community centers including Women and Children Clinics (WIC), primary care clinics and daycare centers in the upper Midwest region. Outcome measures included Forsyth Child Vulnerability Scale (CVS), Thomasgard Parent Protection Scale (PPS) scores, and healthcare utilization (HCU). Potential covariates included history of life-threatening illness, child and maternal demographics, and maternal stress and depression using the Center for Epidemiologic Studies Depression Scale (CESD). HCU (p=0.02) and the PPS subscales of supervision (p=0.003) and separation (p=0.03) were significant predictors of PPCV in mothers of 3-8 years old children with late-preterm history. Age of the child (p=0.008) and CVS scores (p=0.005) were significant predictors of POP. Maternal age (p=0.04), stress (p=0.04), and CVS scores (p=0.003) were significant predictors of HCU. Dependence, a subscale of the PPS, correlated with the child's age and gender even after controlling for age. History of late-preterm did not predict MPCV, MOP, or HCU in healthy children. Future research is needed in larger more diverse samples to better understand causal relationships and develop strategies to lessen risks of MPCV and MOP. Published by Elsevier Ireland Ltd.

  17. Predictive value of late decelerations for fetal acidemia in unselective low-risk pregnancies.

    Science.gov (United States)

    Sameshima, Hiroshi; Ikenoue, Tsuyomu

    2005-01-01

    We evaluated the clinical significance of late decelerations (LD) of intrapartum fetal heart rate (FHR) monitoring to detect low pH (LD (occasional, 50%; recurrent, > or = 50%) and severity (reduced baseline FHR accelerations and variability) of LD, and low pH (test, and one-way analysis of variance with the Bonferroni/Dunn test. In the 5522 low-risk pregnancies, 301 showed occasional LD and 99 showed recurrent LD. Blood gases and pH values deteriorated as the incidence of LD increased and as baseline accelerations or variability was decreased. Positive predictive value for low pH (LD, and > 50% in recurrent LD with no baseline FHR accelerations and reduced variability. In low-risk pregnancies, information on LD combined with acceleration and baseline variability enables us to predict the potential incidence of fetal acidemia.

  18. High School Football and Late-Life Risk of Neurodegenerative Syndromes, 1956-1970.

    Science.gov (United States)

    Janssen, Pieter H H; Mandrekar, Jay; Mielke, Michelle M; Ahlskog, J Eric; Boeve, Bradley F; Josephs, Keith; Savica, Rodolfo

    2017-01-01

    To assess whether athletes who played American varsity high school football between 1956 and 1970 have an increased risk of neurodegenerative diseases later in life. We identified all male varsity football players between 1956 and 1970 in the public high schools of Rochester, Minnesota, and non-football-playing male varsity swimmers, wrestlers, and basketball players. Using the medical records linkage system of the Rochester Epidemiology Project, we ascertained the incidence of late-life neurodegenerative diseases: dementia, parkinsonism, and amyotrophic lateral sclerosis. We also recorded medical record-documented head trauma during high school years. We identified 296 varsity football players and 190 athletes engaging in other sports. Football players had an increased risk of medically documented head trauma, especially if they played football for more than 1 year. Compared with nonfootball athletes, football players did not have an increased risk of neurodegenerative disease overall or of the individual conditions of dementia, parkinsonism, and amyotrophic lateral sclerosis. In this community-based study, varsity high school football players from 1956 to 1970 did not have an increased risk of neurodegenerative diseases compared with athletes engaged in other varsity sports. This was from an era when there was a generally nihilistic view of concussion dangers, less protective equipment, and no prohibition of spearing (head-first tackling). However, the size and strength of players from previous eras may not be comparable with that of current high school athletes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  19. Regional spore dispersal as a factor in disease risk warnings for potato late blight: A proof of concept

    NARCIS (Netherlands)

    Skelsey, P.; Kessel, G.J.T.; Holtslag, A.A.M.; Moene, A.F.; Werf, van der W.

    2009-01-01

    This study develops and tests a novel approach for including regional risk factors in operational disease risk warnings against potato late blight. The central premise is that fungicide inputs can be reduced by omitting applications on days when conditions are unsuitable for the atmospheric

  20. Regional spore dispersal as a factor in disease risk warnings for potato late blight : A proof of concept

    NARCIS (Netherlands)

    Skelsey, P.; Kessel, G. J. T.; Holtslag, A. A. M.; Moene, A. F.; van der Werf, W.

    2009-01-01

    This study develops and tests a novel approach for including regional risk factors in operational disease risk warnings against potato late blight. The central premise is that fungicide inputs can be reduced by omitting applications on days when conditions are unsuitable for the atmospheric

  1. High-school football and late-life risk of neurodegenerative syndromes, 1956–1970

    Science.gov (United States)

    Janssen, Pieter HH; Mandrekar, Jay; Mielke, Michelle M; Ahlskog, J. Eric; Boeve, Bradley F; Josephs, Keith; Savica, Rodolfo

    2017-01-01

    BACKGROUND Repeated head trauma has been associated with risk of neurodegenerative diseases. Few studies have evaluated the long-term risk of neurodegenerative diseases in collision sports like football. OBJECTIVE To assess whether athletes who played American varsity high-school football between 1956 and 1970 have an increased risk of neurodegenerative diseases later in life. PATIENTS AND METHODS We identified all male varsity football players between 1956 and 1970 in the public high schools of Rochester, Minnesota, compared to non-football-playing male varsity swimmers, wrestlers or basketball players. Using the records-linkage system of the Rochester Epidemiology Project, we ascertained the incidence of late-life neurodegenerative diseases: dementia, parkinsonism, or amyotrophic lateral sclerosis. We also recorded medical record-documented head trauma during high school years. RESULTS We identified 296 varsity football players and 190 athletes engaging in other sports. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared to non-football athletes, football players did not have an increased risk of neurodegenerative disease overall, nor the individual conditions of dementia, parkinsonism, or amyotrophic lateral sclerosis. CONCLUSION In this community based study, varsity high school football players from 1956 to 1970 did not have an increased risk of developing neurodegenerative diseases compared with athletes engaged in other varsity sports. This was from an era where there was a generally nihilistic view of concussion dangers, less protective equipment and without prohibition of spearing (head-first tackling). However, size and strength of players from prior eras may not be comparable to current high-school athletes. PMID:27979411

  2. Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia.

    Science.gov (United States)

    Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Maeda, Ayumi; Fischer, Michael A; Hernandez-Diaz, Sonia; Huybrechts, Krista F

    2016-09-01

    β blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to β blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries. We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to β blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications. There were 10 585 (0.5%) pregnancies exposed to β blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the β blocker-exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50-1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07-1.55, respectively). Our findings suggest that neonates born to mothers exposed to β blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia. Copyright © 2016 by the American Academy of Pediatrics.

  3. Late life socioeconomic status and hypertension in an aging cohort: the Atherosclerosis Risk in Communities Study.

    Science.gov (United States)

    McDoom, M Maya; Palta, Priya; Vart, Priya; Juraschek, Stephen P; Kucharska-Newton, Anna; Diez Roux, Ana V; Coresh, Josef

    2018-06-01

    To investigate the association between individual and area-level socioeconomic status and hypertension risk among individuals later in life. We used Cox proportional hazards models to examine the association of socioeconomic status with incident hypertension using race-specific neighborhood socioeconomic status, median household income, and education among 3372 participants (mean age, 61 years) from the Atherosclerosis Risk in Communities Study at Visit 4 (1996-1998). Incident hypertension was defined as self-reported diagnosis or reported use of antihypertensive medications. Over a median follow-up time of 9.4 years, there were 1874 new cases of hypertension (62.1 per 1000 person-years). Overall, being in high as compared with low socioeconomic status categories was associated with a lower risk of developing hypertension in late life, with hazard ratios (95% confidence intervals) of 0.87 (0.77-0.98) for high neighborhood socioeconomic status tertile, 0.79 (0.69-0.90) for high individual income, and 0.75 (0.63-0.89) for college education after adjustment for traditional risk factors. These findings were consistent and robust whenever accounting for competing risks of all-cause mortality. No significant interactions by race and age (dichotomized at age 65) were observed. Among participants free of hypertension in midlife, high neighborhood and individual socioeconomic status are associated with a decreased risk of incident hypertension. Our findings support population-level interventions, such as blood pressure screening at senior centers and faith-based organizations, that are tailored to shift the distribution of blood pressure and reduce hypertension health inequalities among older adults.

  4. Contribution of Socioeconomic Status at 3 Life-Course Periods to Late-Life Memory Function and Decline: Early and Late Predictors of Dementia Risk.

    Science.gov (United States)

    Marden, Jessica R; Tchetgen Tchetgen, Eric J; Kawachi, Ichiro; Glymour, M Maria

    2017-10-01

    Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (β = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, β = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

    Science.gov (United States)

    Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2015-01-01

    We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Late language emergence in 24-month-old twins: heritable and increased risk for late language emergence in twins.

    Science.gov (United States)

    Rice, Mabel L; Zubrick, Stephen R; Taylor, Catherine L; Gayán, Javier; Bontempo, Daniel E

    2014-06-01

    This study investigated the etiology of late language emergence (LLE) in 24-month-old twins, considering possible twinning, zygosity, gender, and heritability effects for vocabulary and grammar phenotypes. A population-based sample of 473 twin pairs participated. Multilevel modeling estimated means and variances of vocabulary and grammar phenotypes, controlling for familiality. Heritability was estimated with DeFries-Fulker regression and variance components models to determine effects of heritability, shared environment, and nonshared environment. Twins had lower average language scores than norms for single-born children, with lower average performance for monozygotic than dizygotic twins and for boys than girls, although gender and zygosity did not interact. Gender did not predict LLE. Significant heritability was detected for vocabulary (0.26) and grammar phenotypes (0.52 and 0.43 for boys and girls, respectively) in the full sample and in the sample selected for LLE (0.42 and 0.44). LLE and the appearance of Word Combinations were also significantly heritable (0.22-0.23). The findings revealed an increased likelihood of LLE in twin toddlers compared with single-born children that is modulated by zygosity and gender differences. Heritability estimates are consistent with previous research for vocabulary and add further suggestion of heritable differences in early grammar acquisition.

  7. Effectiveness of Prescription-Based CNS Stimulants on Hospitalization in Patients With Schizophrenia

    DEFF Research Database (Denmark)

    Rohde, Christopher; Polcwiartek, Christoffer; Asztalos, Marton

    2018-01-01

    were used to investigate the effectiveness of CNS stimulants in patients with schizophrenia between 1995 and 2014; a mirror-image model with 605 individuals, using paired t tests and Wilcoxon signed rank tests, and a follow-up study with 789 individuals, using a conditional risk-set model. RESULTS: CNS...

  8. CNS metabolism in high-risk drug abuse, German version. Insights gained from "1H- and "3"1P MRS and PET

    International Nuclear Information System (INIS)

    Bodea, S.V.

    2017-01-01

    High-risk drug consumption is a considerable problem for public health actors in industrialised countries. The latest trends show a market tendency towards diversification and increasing demand for high-purity synthetic drugs. Whilst most consumers seek medical help after cannabis use, it is high-risk drugs like cocaine, heroin and amphetamines that account for most of the 1000 drug-related deaths that occur in Germany every year. This article presents the most prominent in vivo cerebral metabolic information in cocaine, heroin and methamphetamine users provided by MRI spectroscopy and PET imaging. We reviewed the literature reporting neuroimaging studies of in vivo metabolic data for methamphetamine, cocaine and heroin consumption published up to March 2017. The search was conducted using PubMed with the following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET. MRI and PET are indispensable tools in gauging brain metabolic response to illegal drug abuse. Future breakthroughs in this field will most likely come from the investigation of novel neurotransmitter systems in PET and imaging phosphorus and carbon metabolites in MRI. (orig.) [de

  9. Identifying Risk Factors for Late-Onset (50+) Alcohol Use Disorder and Heavy Drinking: A Systematic Review.

    Science.gov (United States)

    Emiliussen, Jakob; Nielsen, Anette Søgaard; Andersen, Kjeld

    2017-10-15

    This systematic review seeks to expand the description and understanding of late-onset AUD and asks "Which risk factors have been reported for late-onset heavy drinking and AUD?" Using PRISMA guidelines, a literature review and search was performed on May 19, 2015 using the following databases: MEDLINE, EMBASE, PubMed, and PsychInfo. Nine studies were included in the final review. The search revealed that only very few studies have been conducted. Hence, the evidence is limited but suggests that stress, role/identity loss, and friends' approval of drinking are associated with an increased risk for late-onset AUD or heavy drinking, whereas retirement, death of a spouse or a close relative does not increase the risk. Inherent differences in measurements and methodologies precluded a meta-analysis. Therefore, the results presented here are descriptive in nature. Most studies base their conclusions on a certain preconception of older adults with alcohol problems, which leads to a row of circular arguments. The factors that have been measured seem to have changed over time. There has been a lack of focus on the field of late-onset AUD since the 1970s, which possibly has led to misrepresentations and preconceptions on the complex nature of late-onset AUD. There is limited evidence for any specific risk factor for late-onset AUD or heavy drinking. We suggest the adoption of a qualitative approach to uncover what is intrinsic to late-onset AUD followed by quantitative studies with more agreement on methods and definitions.

  10. Late-presenting dural tear: incidence, risk factors, and associated complications.

    Science.gov (United States)

    Durand, Wesley M; DePasse, J Mason; Kuris, Eren O; Yang, JaeWon; Daniels, Alan H

    2018-04-18

    Unrecognized and inadequately repaired intraoperative durotomies may lead to cerebrospinal fluid leak, pseudomeningocele, and other complications. Few studies have investigated durotomy that is unrecognized intraoperatively and requires additional postoperative management (hereafter, late-presenting dural tear [LPDT]), although estimates of LPDT range from 0.6 to 8.3 per 1,000 spinal surgeries. These single-center studies are based on relatively small sample sizes for an event of this rarity, all with <10 patients experiencing LPDT. This investigation is the largest yet conducted on LPDT, and sought to identify incidence, risk factors for, and complications associated with LPDT. This observational cohort study employed the American College of Surgeons National Surgical Quality Improvement Program dataset (years 2012-2015). Patients who underwent spine surgery were identified based on presence of primary listed Current Procedural Terminology (CPT) codes corresponding to spinal fusion or isolated posterior decompression without fusion. The primary variable in this study was occurrence of LPDT, identified as reoperation or readmission with durotomy-specific CPT or International Classification of Diseases, Ninth Revision, Clinical Modification codes but without durotomy codes present for the index procedure. Descriptive statistics were generated. Bivariate and multivariate analyses were conducted using chi-square tests and multiple logistic regression, respectively, generating both risk factors for LPDT and independent association of LPDT with postoperative complications. Statistical significance was defined as p<.05. In total, 86,212 patients were analyzed. The overall rate of reoperation or readmission without reoperation for LPDT was 2.0 per 1,000 patients (n=174). Of LPDT patients, 97.7% required one or more unplanned reoperations (n=170), and 5.7% of patients (n=10) required two reoperations. On multivariate analysis, lumbar procedures (odds ratio [OR] 2.79, p

  11. Association between obesity indices and cardiovascular risk factors in late adolescence in the Seychelles.

    Science.gov (United States)

    Bovet, Pascal; Arlabosse, Tiphaine; Viswanathan, Bharathi; Myers, Gary

    2012-11-07

    The ability of different obesity indices to predict cardiovascular risk is still debated in youth and few data are available in sub Saharan Africa. We compared the associations between several indices of obesity and cardiovascular risk factors (CVRFs) in late adolescence in the Seychelles. We measured body mass index (BMI), waist circumference, waist/hip ratio (WHiR), waist/height ratio (WHtR) and percent fat mass (by bioimpedance) and 6 CVRFs (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting blood glucose and uric acid) in 423 youths aged 19-20 years from the general population. The prevalence of overweight/obesity and several CVRFs was high, with substantial sex differences. Except for glucose in males and LDL-cholesterol in females, all obesity indices were associated with CVRFs. BMI consistently predicted CVRFs at least as well as the other indices. Linear regression on BMI had standardized regression coefficients of 0.25-0.36 for most CVRFs (pP90). There was an elevated prevalence of obesity and of several CVRFs in youths in Seychelles. BMI predicted single or combined CVRFs at least as well as other simple obesity indices.

  12. Association between obesity indices and cardiovascular risk factors in late adolescence in the Seychelles

    Directory of Open Access Journals (Sweden)

    Bovet Pascal

    2012-11-01

    Full Text Available Abstract Background The ability of different obesity indices to predict cardiovascular risk is still debated in youth and few data are available in sub Saharan Africa. We compared the associations between several indices of obesity and cardiovascular risk factors (CVRFs in late adolescence in the Seychelles. Methods We measured body mass index (BMI, waist circumference, waist/hip ratio (WHiR, waist/height ratio (WHtR and percent fat mass (by bioimpedance and 6 CVRFs (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting blood glucose and uric acid in 423 youths aged 19–20 years from the general population. Results The prevalence of overweight/obesity and several CVRFs was high, with substantial sex differences. Except for glucose in males and LDL-cholesterol in females, all obesity indices were associated with CVRFs. BMI consistently predicted CVRFs at least as well as the other indices. Linear regression on BMI had standardized regression coefficients of 0.25-0.36 for most CVRFs (pP90. Conclusion There was an elevated prevalence of obesity and of several CVRFs in youths in Seychelles. BMI predicted single or combined CVRFs at least as well as other simple obesity indices.

  13. Parental Separation and Cardiometabolic Risk Factors in Late Adolescence: A Cross-Cohort Comparison.

    Science.gov (United States)

    Soares, Ana Luiza Gonçalves; Gonçalves, Helen; Matijasevich, Alicia; Sequeira, Maija; Smith, George Davey; Menezes, Ana M B; Assunção, Maria Cecília; Wehrmeister, Fernando C; Fraser, Abigail; Howe, Laura D

    2017-05-15

    The aim of this study was to explore the association between parental separation during childhood (up to 18 years of age) and cardiometabolic risk factors (body mass index, fat mass index, blood pressure, physical activity, smoking, and alcohol consumption) in late adolescence using a cross-cohort comparison and to explore whether associations differ according to the age at which the parental separation occurred and the presence or absence of parental conflict prior to separation. Data from the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom) (1991-2011) and the 1993 Pelotas Birth Cohort (Brazil) (1993-2011) were used. The associations of parental separation with children's cardiometabolic risk factors were largely null. Higher odds of daily smoking were observed in both cohorts for those adolescents whose parents separated (for ALSPAC, odds ratio = 1.46; for Pelotas Birth Cohort, odds ratio = 1.98). Some additional associations were observed in the Pelotas Birth Cohort but were generally in the opposite direction to our a priori hypothesis: Parental separation was associated with lower blood pressure and fat mass index, and with more physical activity. No consistent differences were observed when analyses were stratified by child's age at parental separation or parental conflict. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  14. Nanomedicines for the Treatment of CNS Diseases.

    Science.gov (United States)

    Reynolds, Jessica L; Mahato, Ram I

    2017-03-01

    Targeting and delivering macromolecular therapeutics to the central nervous system (CNS) has been a major challenge. The blood-brain barrier (BBB) is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Therefore, much effort has been channelled into improving transport of therapeutics across the BBB and into the CNS including the use of nanoparticles. In this thematic issue, several reviews and original research are presented that address "Nanomedicines for CNS Diseases." The articles in this issue are concentrated on either CNS-HIV disease or CNS tumors. In regards to CNS-HIV disease, there are two reviews that discuss the role of nanoparticles for improving the delivery of HIV therapeutics to the CNS. In addition, there are two original articles focusing on therapies for CNS-HIV, one of them uses nanoparticles for delivery of siRNA specific to a key protein in autophagy to microglia, and another discusses nanoparticle delivery of a soluble mediator to suppress neuroinflammation. Furthermore, a comprehensive review about gene therapy for CNS neurological diseases is also included. Finally, this issue also includes review articles on enhanced drug targeting to CNS tumors. These articles include a review on the use of nanoparticles for CNS tumors, a review on functionalization (ligands) of nanoparticles for drug targeting to the brain tumor by overcoming BBB, and the final review discusses the use of macrophages as a delivery vehicle to CNS tumors. This thematic issue provides a wealth of knowledge on using nanomedicines for CNS diseases.

  15. Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa.

    Directory of Open Access Journals (Sweden)

    Paul K Drain

    Full Text Available After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults.We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3. We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare" on presentation with late-stage HIV disease.Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6% presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4, were male (AOR 1.7, 95% CI 1.2-2.3, worked outside the home (AOR 1.5, 95% CI 1.1-2.1, perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1, and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9 had higher odds of late-stage HIV disease presentation.Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

  16. Risk factors for new-onset late postpartum preeclampsia in women without a history of preeclampsia.

    Science.gov (United States)

    Bigelow, Catherine A; Pereira, Guilherme A; Warmsley, Amber; Cohen, Jennifer; Getrajdman, Chloe; Moshier, Erin; Paris, Julia; Bianco, Angela; Factor, Stephanie H; Stone, Joanne

    2014-04-01

    Risk factors for the development of new-onset late postpartum preeclampsia (LPP) in women without any history of preeclampsia are not known. Because identification of women who are at risk may lead to an earlier diagnosis of disease and improved maternal outcomes, this study identified risk factors (associated patient characteristics) for new-onset LPP. A case-control study of 34 women with new-onset LPP and 68 women without new-onset LPP after normal delivery, who were matched on date of delivery, was conducted at Mount Sinai Hospital, New York, NY. Data were collected by chart review. Exact conditional logistic regression identified patient characteristics that were associated with new-onset LPP. New-onset LPP was associated with age ≥40 years (adjusted odds ratio, 24.83; 95% confidence interval [CI], 1.43-infinity; P = .03), black race (adjusted odds ratio, 78.35; 95% CI, 7.25-infinity; P infinity; P = .001), final pregnancy body mass index of ≥30 kg/m(2) (adjusted odds ratio, 13.38; 95% CI, 1.87-infinity; P = .01), and gestational diabetes mellitus (adjusted odds ratio, 72.91; 95% CI, 5.52-infinity; P < .001). As predictive tests for new-onset LPP, the sensitivity and specificity of having ≥1 of these characteristics was 100% and 59%, respectively, and the sensitivity and specificity of having ≥2 was 56% and 93%, respectively. Older age, black race, Latino ethnicity, obesity, and a pregnancy complicated by gestational diabetes mellitus all are associated positively with the development of new-onset LPP. Closer observation may be warranted in these populations. Copyright © 2014 Mosby, Inc. All rights reserved.

  17. Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

    Science.gov (United States)

    Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

    2016-07-02

    Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

  18. An invertebrate model for CNS drug discovery

    DEFF Research Database (Denmark)

    Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré

    2015-01-01

    BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery....

  19. Radiation risk of tissue late effects, a net consequence of probabilities of various cellular responses

    International Nuclear Information System (INIS)

    Feinendegen, L.E.

    1991-01-01

    Late effects from the exposure to low doses of ionizing radiation are hardly or not at all observed in man mainly due to the low values of risk coefficients that preclude statistical analyses of data from populations that are exposed to doses less than 0.2 Gy. In order to arrive at an assessment of potential risk from radiation exposure in the low dose range, the microdosimetry approach is essential. In the low dose range, ionizing radiation generates particle tracks, mainly electrons, which are distributed rather heterogeneously within the exposed tissue. Taking the individual cell as the elemental unit of life, observations and calculations of cellular responses to being hit by energy depositions events from low LET type are analysed. It emerges that besides the probability of a hit cell to sustain a detrimental effect with the consequense of malignant transformation there are probabilities of various adaptive responses that equipp the hit cell with a benefit. On the one hand, an improvement of cellular radical detoxification was observed in mouse bone marrow cells; another adaptive response pertaining to improved DNA repair, was reported for human lymphocytes. The improved radical detoxification in mouse bone marrow cells lasts for a period of 5-10 hours and improved DNA repair in human lymphocytes was seen for some 60 hours following acute irradiation. It is speculated that improved radical detoxification and improved DNA repair may reduce the probability of spontaneous carcinogenesis. Thus it is proposed to weigh the probability of detriment for a hit cell within a multicellular system against the probability of benefit through adaptive responses in other hit cells in the same system per radiation exposure. In doing this, the net effect of low doses of low LET radiation in tissue with individual cells being hit by energy deposition events could be zero or even beneficial. (orig./MG)

  20. Late Neolithic Mondsee Culture in Austria: living on lakes and living with flood risk?

    Directory of Open Access Journals (Sweden)

    T. Swierczynski

    2013-07-01

    Full Text Available Neolithic and Bronze Age lake dwellings in the European Alps became recently protected under the UNESCO World Heritage. However, only little is known about the cultural history of the related pre-historic communities, their adaptation strategies to environmental changes and particularly about the almost synchronous decline of many of these settlements around the transition from the Late Neolithic to the Early Bronze Age. For example, there is an ongoing debate whether the abandonment of Late Neolithic lake dwellings at Lake Mondsee (Upper Austria was caused by unfavourable climate conditions or a single catastrophic event. Within the varved sediments of Lake Mondsee, we investigated the occurrence of intercalated detrital layers from major floods and debris flows to unravel extreme surface runoff recurrence during the Neolithic settlement period. A combination of detailed sediment microfacies analysis and μXRF element scanning allows distinguishing debris flow and flood deposits. A total of 60 flood and 12 debris flow event layers was detected between 7000 and 4000 varve years (vyr BP. Compared to the centennial- to millennial-scale average, a period of increased runoff event frequency can be identified between 5900 and 4450 vyr BP. Enhanced flood frequency is accompanied by predominantly siliciclastic sediment supply between ca. 5500 and 5000 vyr BP and enhanced dolomitic sediment supply between 4900 and 4500 vyr BP. A change in the location and the construction technique of the Neolithic lake dwellings at Lake Mondsee can be observed during the period of higher flood frequency. While lake dwellings of the first settlement period (ca. 5800–5250 cal. yr BP were constructed directly on the wetlands, later constructions (ca. 5400–4700 cal. yr BP were built on piles upon the water, possibly indicating an adaptation to either increased flood risk or a general increase of the lake level. However, our results also indicate that other than

  1. Differential risk for late adolescent conduct problems and mood dysregulation among children with early externalizing behavior problems.

    Science.gov (United States)

    Okado, Yuko; Bierman, Karen L

    2015-05-01

    To investigate the differential emergence of antisocial behaviors and mood dysregulation among children with externalizing problems, the present study prospectively followed 317 high-risk children with early externalizing problems from school entry (ages 5-7) to late adolescence (ages 17-19). Latent class analysis conducted on their conduct and mood symptoms in late adolescence revealed three distinct patterns of symptoms, characterized by: 1) criminal offenses, conduct disorder symptoms, and elevated anger ("conduct problems"), 2) elevated anger, dysphoric mood, and suicidal ideation ("mood dysregulation"), and 3) low levels of severe conduct and mood symptoms. A diathesis-stress model predicting the first two outcomes was tested. Elevated overt aggression at school entry uniquely predicted conduct problems in late adolescence, whereas elevated emotion dysregulation at school entry uniquely predicted mood dysregulation in late adolescence. Experiences of low parental warmth and peer rejection in middle childhood moderated the link between early emotion dysregulation and later mood dysregulation but did not moderate the link between early overt aggression and later conduct problems. Thus, among children with early externalizing behavior problems, increased risk for later antisocial behavior or mood dysfunction may be identifiable in early childhood based on levels of overt aggression and emotion dysregulation. For children with early emotion dysregulation, however, increased risk for mood dysregulation characterized by anger, dysphoric mood, and suicidality--possibly indicative of disruptive mood dysregulation disorder--emerges only in the presence of low parental warmth and/or peer rejection during middle childhood.

  2. Risk factors and outcomes for late presentation for HIV-positive persons in europe

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Lundgren, Jens D; Sabin, Miriam Lewis

    2013-01-01

    Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.......Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality....

  3. A philosophy for CNS radiotracer design.

    Science.gov (United States)

    Van de Bittner, Genevieve C; Ricq, Emily L; Hooker, Jacob M

    2014-10-21

    Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available

  4. Acne in late adolescence is not associated with a raised risk of subsequent malignant melanoma among men.

    Science.gov (United States)

    Mota Garcia, Teresa; Hiyoshi, Ayako; Udumyan, Ruzan; Sjöqvist, Hugo; Fall, Katja; Montgomery, Scott

    2017-12-01

    To evaluate the association of acne in late adolescence with the risk for subsequent malignant melanoma (MM) in men. Swedish register-based cohort study of 242,096 males born between 1952 and 1956, who took part in compulsory assessments for Swedish military conscription in late adolescence between 1969 and 1975, with subsequent diagnoses of MM (n=1,058) up to December 31, 2009. Covariates included measures of childhood circumstances and information from adolescence on presence of acne, physical fitness, cognitive function, body mass index (BMI), and a summary of diagnoses. Cox regression was used for the analysis. In total 1,058 men were diagnosed with MM. Acne was not associated with subsequent MM, with an adjusted hazard ratio (and 95% confidence interval) of 0.95 (0.61 to 1.49). Men with parents who were agricultural workers, and men who lived in northern Sweden, had lower physical fitness, or lower cognitive function had a lower risk of MM. Overweight and obesity was associated with a raised risk, with an adjusted hazard ratio of 1.39 (1.14, 1.71). Acne in late adolescence is unlikely to represent a raised risk for subsequent MM in men. Overweight or obesity was identified as a raised risk for MM, possibly due to the associated increased skin surface area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ismail, Tevfik F; Jabbour, Andrew; Gulati, Ankur; Mallorie, Amy; Raza, Sadaf; Cowling, Thomas E; Das, Bibek; Khwaja, Jahanzaib; Alpendurada, Francisco D; Wage, Ricardo; Roughton, Michael; McKenna, William J; Moon, James C; Varnava, Amanda; Shakespeare, Carl; Cowie, Martin R; Cook, Stuart A; Elliott, Perry; O'Hanlon, Rory; Pennell, Dudley J; Prasad, Sanjay K

    2014-12-01

    Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM. We conducted a prospective cohort study in a tertiary referral centre. Consecutive patients with HCM (n=711, median age 56.3 years, IQR 46.7-66.6; 70.0% male) underwent LGE-CMR and were followed for a median 3.5 years. The primary end point was SCD or aborted SCD. Overall, 471 patients (66.2%) had myocardial fibrosis (median 5.9% of left ventricular mass, IQR: 2.2-13.3). Twenty-two (3.1%) reached the primary end point. The extent but not the presence of fibrosis was a significant univariable predictor of the primary end point (HR per 5% LGE: 1.24, 95% CI 1.06 to 1.45; p=0.007 and HR for LGE: 2.69, 95% CI 0.91 to 7.97; p=0.073, respectively). However, on multivariable analysis, only LV-EF remained statistically significant (HR: 0.92, 95% CI 0.89 to 0.95; p<0.001). For the secondary outcome of cardiovascular mortality/aborted SCD, the presence and the amount of fibrosis were significant predictors on univariable but not multivariable analysis after adjusting for LV-EF and non-sustained ventricular tachycardia. The amount of myocardial fibrosis was a strong univariable predictor of SCD risk. However, this effect was not maintained after adjusting for LV-EF. Further work is required to elucidate the interrelationship between fibrosis and traditional predictors of outcome in HCM. 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.

  6. Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

    Science.gov (United States)

    Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

    2013-12-01

    Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

  7. microRNAs in CNS disorders

    DEFF Research Database (Denmark)

    Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes

    2009-01-01

    RNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...

  8. Intralesional Injection of Collagenase Clostridium histolyticum May Increase the Risk of Late-Onset Penile Fracture.

    Science.gov (United States)

    Beilan, Jonathan A; Wallen, Jared J; Baumgarten, Adam S; Morgan, Kevin N; Parker, Justin L; Carrion, Rafael E

    2018-04-01

    The use of intralesional injection of collagenase Clostridium histolyticum (CCH) has become a valid treatment option in the management of Peyronie's disease (PD). Multiple studies have shown the drug's safety and efficacy. However, sparse literature exists on the utility of the injection protocol's 14-day "observation period," in which patients are instructed to abstain from all sexual activity. To summarize the contemporary literature and report on our series of patients treated with CCH in an effort to explore the effectiveness of the postinjection observation period. We retrospectively reviewed the clinical course of men treated with at least one CCH injection at our institution from April 2014 through February 2017. The main outcome measure for our cohort was complication rate (hematoma, fracture). Secondary outcomes included progression to corrective surgery. Of the 102 patients treated, 5 (4.9%) developed a corporal fracture. Four of these occurred outside the 14-day observation period. One fracture was managed conservatively and the rest underwent surgical exploration and repair. Twelve penile hematomas were reported; one of these patients was surgically explored because of suspicious magnetic resonance imaging findings. Seven patients (6.9%) progressed to corrective surgery. Penile hematoma and corporal fracture are serious complications that must be discussed with patients before initiation of intralesional CCH treatment. Little evidence exists to direct physicians on the proper management of post-CCH penile fractures; many caregivers and patients elect to treat these injuries conservatively and avoid surgical exploration. Further studies are warranted to generate discussion and reassessment regarding the safety and effectiveness of this 14-day observation period. Beilan JA, Wallen JJ, Baumgarten AS, Morgan KN, Parker JL, Carrion RE. Intralesional Injection of Collagenase Clostridium histolyticum May Increase the Risk of Late-Onset Penile Fracture. Sex

  9. Melanocortin signaling in the CNS directly regulates circulating cholesterol

    OpenAIRE

    Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

    2010-01-01

    Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

  10. Applications of Genomic Sequencing in Pediatric CNS Tumors.

    Science.gov (United States)

    Bavle, Abhishek A; Lin, Frank Y; Parsons, D Williams

    2016-05-01

    Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characterization of multiple tumor types, provided new insights into the genetic basis of these cancers, and prompted innovative strategies that are changing the management paradigm in pediatric neuro-oncology. Genomic tests have begun to affect medical decision making in a number of ways, from delineating histopathologically similar tumor types into distinct molecular subgroups that correlate with clinical characteristics, to guiding the addition of novel therapeutic agents for patients with high-risk or poor-prognosis tumors, or alternatively, reducing treatment intensity for those with a favorable prognosis. Genomic sequencing has also had a significant impact on translational research strategies in pediatric CNS tumors, resulting in wide-ranging applications that have the potential to direct the rational preclinical screening of novel therapeutic agents, shed light on tumor heterogeneity and evolution, and highlight differences (or similarities) between pediatric and adult CNS tumors. Finally, in addition to allowing the identification of somatic (tumor-specific) mutations, the analysis of patient-matched constitutional (germline) DNA has facilitated the detection of pathogenic germline alterations in cancer genes in patients with CNS tumors, with critical implications for genetic counseling and tumor surveillance strategies for children with familial predisposition syndromes. As our understanding of the molecular landscape of pediatric CNS tumors continues to advance, innovative applications of genomic sequencing hold significant promise for further improving the care of children with these cancers.

  11. Late effects of craniospinal irradiation for standard risk medulloblastoma in paediatric patients: A comparison of treatment techniques

    International Nuclear Information System (INIS)

    Leman, J.

    2016-01-01

    Background: Survival rates for standard risk medulloblastoma are favourable, but craniospinal irradiation (CSI) necessary to eradicate microscopic spread causes life limiting late effects. Aims: The aim of this paper is to compare CSI techniques in terms of toxicity and quality of life for survivors. Methods and materials: A literature search was conducted using synonyms of ‘medulloblastoma’, ’craniospinal’, ‘radiotherapy’ and ‘side effects’ to highlight 29 papers that would facilitate this discussion. Results and discussion: Intensity modulated radiotherapy (IMRT), tomotherapy and protons all provide CSI which can reduce dose to normal tissue, however photon methods cannot eliminate exit dose as well as protons can. Research for each technique requires longer term follow up in order to prove that survival rates remain high whilst reducing late effects. Findings/conclusion: Proton therapy is the superior method of CSI in term of late effects, but more research is needed to evidence this. Until proton therapy is available in the UK IMRT should be utilised. - Highlights: • Craniospinal irradiation is vital in the treatment of medulloblastoma. • Survivors often suffer long term side effects which reduce quality of life. • Tomotherapy, IMRT and proton therapy reduce late effects by sparing normal tissue. • Proton therapy offers superior dose distribution but further research is necessary. • IMRT should be employed for photon radiotherapy.

  12. Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort

    Science.gov (United States)

    2013-01-01

    Background To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. Methods We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. Results Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13). Conclusions Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease. PMID:23663420

  13. Late-Life and Life History Predictors of Older Adults of High-Risk Alcohol Consumption and Drinking Problems

    Science.gov (United States)

    Moos, Rudolf H.; Schutte, Kathleen K.; Brennan, Penny L.; Moos, Bernice S.

    2009-01-01

    Aims This prospective, longitudinal study focused on late-life and life history predictors of high-risk alcohol consumption and drinking problems during a 20-year interval as adults matured from age 55–65 to age 75–85. Design, Setting, Participants A sample of older community residents (N=719) who had consumed alcohol in the past year or shortly before was surveyed at baseline and 10 years and 20 years later. Measurements At each contact point, participants completed an inventory that assessed their alcohol consumption, drinking problems, and personal and life context factors. Participants also provided information about their life history of drinking and help-seeking. Results Older adults who, at baseline, had more friends who approved of drinking, relied on substances for tension reduction, and had more financial resources were more likely to engage in high-risk alcohol consumption and to incur drinking problems at 10-year and 20-year follow-ups. With respect to life history factors, drinking problems by age 50 were associated with a higher likelihood of late-life high-risk alcohol consumption and drinking problems; having tried to cut down on drinking and participation in Alcoholics Anonymous were associated with a lower likelihood of high-risk consumption and problems. Conclusion Specific late-life and life history factors can identify older adults likely to engage in excessive alcohol consumption 10 and 20 years later. Targeted screening that considers current alcohol consumption and life context, and history of drinking problems and help-seeking, could help identify older adults at higher risk for excessive or problematic drinking. PMID:19969428

  14. Late-life and life history predictors of older adults' high-risk alcohol consumption and drinking problems.

    Science.gov (United States)

    Moos, Rudolf H; Schutte, Kathleen K; Brennan, Penny L; Moos, Bernice S

    2010-04-01

    This prospective, longitudinal study focused on late-life and life history predictors of high-risk alcohol consumption and drinking problems during a 20-year interval as adults matured from age 55-65 to 75-85. A sample of older community residents (N=719) who had consumed alcohol in the past year or shortly before was surveyed at baseline and 10 and 20 years later. At each contact point, participants completed an inventory that assessed their alcohol consumption, drinking problems, and personal and life context factors. Participants also provided information about their life history of drinking and help-seeking. Older adults who, at baseline, had more friends who approved of drinking, relied on substances for tension reduction, and had more financial resources were more likely to engage in high-risk alcohol consumption and to incur drinking problems at 10- and 20-year follow-ups. With respect to life history factors, drinking problems by age 50 were associated with a higher likelihood of late-life high-risk alcohol consumption and drinking problems; having tried to cut down on drinking and participation in Alcoholics Anonymous were associated with a lower likelihood of high-risk consumption and problems. Specific late-life and life history factors can identify older adults likely to engage in excessive alcohol consumption 10 and 20 years later. Targeted screening that considers current alcohol consumption and life context, and history of drinking problems and help-seeking, could help identify older adults at higher risk for excessive or problematic drinking. Published by Elsevier Ireland Ltd.

  15. The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women.

    Science.gov (United States)

    Hoenderboom, B M; van Oeffelen, A A M; van Benthem, B H B; van Bergen, J E A M; Dukers-Muijrers, N H T M; Götz, H M; Hoebe, C J P A; Hogewoning, A A; van der Klis, F R M; van Baarle, D; Land, J A; van der Sande, M A B; van Veen, M G; de Vries, F; Morré, S A; van den Broek, I V F

    2017-04-11

    Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection (STI) among young women, can result in serious sequelae. Although the course of infection is often asymptomatic, CT may cause pelvic inflammatory disease (PID), leading to severe complications, such as prolonged time to pregnancy, ectopic pregnancy, and tubal factor subfertility. The risk of and risk factors for complications following CT-infection have not been assessed in a long-term prospective cohort study, the preferred design to define infections and complications adequately. In the Netherlands Chlamydia Cohort Study (NECCST), a cohort of women of reproductive age with and without a history of CT-infection is followed over a minimum of ten years to investigate (CT-related) reproductive tract complications. This study is a follow-up of the Chlamydia Screening Implementation (CSI) study, executed between 2008 and 2011 in the Netherlands. For NECCST, female CSI participants who consented to be approached for follow-up studies (n = 14,685) are invited, and prospectively followed until 2022. Four data collection moments are foreseen every two consecutive years. Questionnaire data and blood samples for CT-Immunoglobulin G (IgG) measurement are obtained as well as host DNA to determine specific genetic biomarkers related to susceptibility and severity of infection. CT-history will be based on CSI test outcomes, self-reported infections and CT-IgG presence. Information on (time to) pregnancies and the potential long-term complications (i.e. PID, ectopic pregnancy and (tubal factor) subfertility), will be acquired by questionnaires. Reported subfertility will be verified in medical registers. Occurrence of these late complications and prolonged time to pregnancy, as a proxy for reduced fertility due to a previous CT-infection, or other risk factors, will be investigated using longitudinal statistical procedures. In the proposed study, the occurrence of late complications following

  16. Risk factors of late cardiogenic shock and mortality in ST-segment elevation myocardial infarction patients

    DEFF Research Database (Denmark)

    Obling, Laust; Frydland, Martin; Hansen, Rikke

    2018-01-01

    BACKGROUND: The incidence of cardiogenic shock (CS) in patients with ST-segment elevation myocardial infarction (STEMI) is as high as 10%. The majority of patients are thought to develop CS after admission (late CS), but the incidence in a contemporary STEMI cohort admitted for primary percutaneo...

  17. Late-life depression: structural brain abnormalities, treatment and risk factors

    NARCIS (Netherlands)

    Janssen, Joost

    2006-01-01

    Major depression is a prevalent disease among the elderly, significantly decreasing the quality of life. The age of first onset of depression can be early in life, so called early-onset depression (EOD), as well as first occur in old age, i.e. late-onset depression (LOD). Some previous studies have

  18. Late Toxicities after Conventional Radiotherapy for Nasopharyngeal Carcinoma: Incidence and Risk Factors

    International Nuclear Information System (INIS)

    Siala, W.; Mnejja, W.; Elloumi, F.; Daoud, J.; Ghorbel, A.; Mnif, J.; Frikha, M.

    2014-01-01

    Background. To determine the incidence and analyze the factors affecting late toxicity for nasopharyngeal carcinoma patients treated with conventional radiotherapy. Patients and Methods. Retrospective analysis was performed on 239 NPC patients treated between 1993 and 2004 in our institution. One hundred and fifty-seven patients were treated with conventional fractionation (2 Gy per fraction, 5 fractions per week) and eighty-two patients with hyperfractionated radiotherapy (1.6 Gy per fraction twice a day, 5 days per week). One hundred fifty nine patients underwent neoadjuvant cisplatin based chemotherapy. Late toxicity was evaluated according to the RTOG/EORTC score. Results. Xerostomia was the most common related complication (98.7%). Neoadjuvant chemotherapy and hyperfractionated radiotherapy did not increase late toxicities. Multivariate analyses showed that radiation dose was a significant factor for hearing impairment, younger age for trismus, initial node status for neck fibrosis, and initial dental hygiene for dental complications. Female gender was associated with significantly higher incidence of trismus and hearing impairment. Conclusion. Conventional radiotherapy was associated with a high rate of late toxicities which affect patients’ quality of life. With the development of three-dimensional conformal radiotherapy and intensity modulated radiotherapy, a reduced incidence of radiation related complications could be expected.

  19. Dynamics of rectal balloon implant shrinkage in prostate VMAT. Influence on anorectal dose and late rectal complication risk

    International Nuclear Information System (INIS)

    Vanneste, Ben G.L.; Wijk, Y. van; Lutgens, L.C.; Limbergen, E.J. van; Lambin, P.; Lin, E.N. van; Beek, K. van de; Hoffmann, A.L.

    2018-01-01

    To assess the effect of a shrinking rectal balloon implant (RBI) on the anorectal dose and complication risk during the course of moderately hypofractionated prostate radiotherapy. In 15 patients with localized prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and prostate-rectum separation. The absolute anorectal volume encompassed by the 2 Gy equieffective 75 Gy isodose (V 75Gy ) was recalculated as well as the mean anorectal dose. The increase in estimated risk of grade 2-3 late rectal bleeding (LRB) between the start and end of treatment was predicted using nomograms. The observed acute and late toxicities were evaluated. A significant shrinkage of RBI volumes was observed, with an average volume of 70.4% of baseline at the end of the treatment. Although the prostate-rectum separation significantly decreased over time, it remained at least 1 cm. No significant increase in V 75Gy of the anorectum was observed, except in one patient whose RBI had completely deflated in the third week of treatment. No correlation between mean anorectal dose and balloon deflation was found. The increase in predicted LRB risk was not significant, except in the one patient whose RBI completely deflated. The observed toxicities confirmed these findings. Despite significant decrease in RBI volume the high-dose rectal volume and the predicted LRB risk were unaffected due to a persistent spacing between the prostate and the anterior rectal wall. (orig.) [de

  20. Effects of x rays on the morphology and physiology of the CNS blood vessels of mice

    Energy Technology Data Exchange (ETDEWEB)

    Gladysz, J [Akademia Medyczna, Poznan (Poland)

    1974-01-01

    Irradiation of the CNS of mice with 4000 to 7600 R produces transitional disorder of the permeability of vascular walls, followed by a permanent (irreversible) degenerative lesion of blood capillaries and the surrounding astrogial cells. Intensity of this alterations may however not be the same in different terminal blood vessels. It is very likely that the above described lesion appearing in the acute phase can be the main cause of further alterations in the CNS which are observed in late phase of postradiation disease.

  1. Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus.

    Science.gov (United States)

    Morel, Nathalie; Lévesque, Kateri; Maltret, Alice; Baron, Gabriel; Hamidou, Mohamed; Orquevaux, Pauline; Piette, Jean-Charles; Barriere, François; Le Bidois, Jérôme; Fermont, Laurent; Fain, Olivier; Theulin, Arnaud; Sassolas, François; Hauet, Quentin; Guettrot-Imbert, Gaëlle; Georgin-Lavialle, Sophie; Deligny, Christophe; Hachulla, Eric; Mouthon, Luc; Le Jeunne, Claire; Ravaud, Philippe; Le Mercier, Delphine; Romefort, Bénédicte; Villain, Elisabeth; Bonnet, Damien; Costedoat-Chalumeau, Nathalie

    2017-12-01

    Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

    Science.gov (United States)

    Hur, Eun-Mi; Lee, Byoung Dae

    2014-12-01

    Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  3. Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

    Directory of Open Access Journals (Sweden)

    Eun-Mi Hur

    2014-12-01

    Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  4. Detailed course of depressive symptoms and risk for developing depression in late adolescents with subthreshold depression: a cohort study

    Directory of Open Access Journals (Sweden)

    Jinnin R

    2016-12-01

    Full Text Available Ran Jinnin,1 Yasumasa Okamoto,1 Koki Takagaki,1 Yoshiko Nishiyama,1 Takanao Yamamura,1 Yuri Okamoto,2 Yoshie Miyake,2 Yoshitake Takebayashi,3 Keisuke Tanaka,4 Yoshinori Sugiura,5 Haruki Shimoda,6 Norito Kawakami,6 Toshi A Furukawa,7 Shigeto Yamawaki1 1Department of Psychiatry and Neurosciences, 2Health Service Center, Hiroshima University, Hiroshima, Japan; 3Risk Analysis Research Center, The Institute of Statistical Mathematics, Tokyo, Japan; 4Graduated School of Education, Joetsu University of Education, Niigata, Japan; 5Graduated School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, Japan; 6Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 7Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan Purpose: Despite its clinical importance, adolescent subthreshold depression remains a largely neglected topic. The aims of this study were to accurately identify the natural course of depressive symptoms and the risk for developing major depressive episode (MDE in late adolescents with subthreshold depression over 1 year.Patients and methods: One hundred and seventy-two participants <20 years of age (mean age: 18.32 years, standard deviation: 0.50, who did not meet the full criteria for an MDE, were selected from 2,494 screened freshmen based on the Beck Depression Inventory, 2nd edition (BDI-II. We conducted a cohort study of three groups (low-, middle-, and high-symptom groups divided based on BDI-II scores, over a 1 year period with the use of bimonthly assessments. Temporal changes of depressive symptoms were analyzed using linear mixed modeling and growth mixture modeling.Results: First, we found that late adolescents with subthreshold depression (high depressive symptoms were split between the increasing and decreasing depressive symptoms groups, whereas the majority of the less-symptoms group remained

  5. Comparing Growth Trajectories of Risk Behaviors from Late Adolescence through Young Adulthood: An Accelerated Design

    Science.gov (United States)

    Brodbeck, Jeannette; Bachmann, Monica S.; Croudace, Tim J.; Brown, Anna

    2013-01-01

    Risk behaviors such as substance use or deviance are often limited to the early stages of the life course. Whereas the onset of risk behavior is well studied, less is currently known about the decline and timing of cessation of risk behaviors of different domains during young adulthood. Prevalence and longitudinal developmental patterning of…

  6. High dose rate brachytherapy for carcinoma of the cervix: risk factors for late rectal complications

    International Nuclear Information System (INIS)

    Uno, Takashi; Itami, Jun; Aruga, Moriyo; Kotaka, Kikuo; Fujimoto, Hajime; Minoura, Shigeki

    1996-01-01

    Purpose/Objective: To determine the incidence of late rectal complications in patients treated with high dose rate brachytherapy for FIGO stage IIB, IIIB carcinoma of the uterine cervix, and to evaluate the treatment factors associated with an increased probability of treatment complications. Materials and Methods: Records of 100 patients with FIGO IIB or IIIB cervical carcinoma treated with definitive irradiation using high dose rate intracavitary brachytherapy (HDR-ICR) between 1977 and 1994 were retrospectively reviewed. For each HDR-ICR session, 6 Gy isodose volume was reconstructed three dimensionally and the following three parameters were determined to represent this isodose volume, length (L); maximum longitudinal distance of 6 Gy isodose area in an oblique frontal plane containing the intrauterine applicator, width (W); maximum width of 6 Gy isodose area in the same plane, height (H); maximum dimension of 6 Gy isodose area perpendicular to the intrauterine applicator determined in the oblique sagittal plane. Point P/Q (2 cm ventral/dorsal from the proximal retention point of the intrauterine source) and point R/S (2 cm ventral/dorsal from the midpoint of the ovoid sources) were also defined retrospectively and HDR-ICR dose at these points were calculated. Statistical analyses were performed to determine the treatment factors predictive of late rectal complications. Results: The 5-year cumulative cause-specific disease-free survival rate was 50% for all, 74% for Stage IIB, and 38% for Stage IIIB, with a significant difference between two FIGO Stages (p=0.0004). Of patients treated for both stages, 30% and 36% had experienced moderate to severe (Grade 2-4) complications at 3 and 5 years, respectively. Average H value (p=0.013) and cumulative point S dose by HDR-ICR (p=0.020) were significantly correlated with the incidence of late rectal complications (Student's t-test), whereas these factors did not significantly affect the probability of pelvic control. No

  7. Adverse CNS-effects of beta-adrenoceptor blockers.

    Science.gov (United States)

    Gleiter, C H; Deckert, J

    1996-11-01

    In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

  8. Identifying Risk Factors for Late-Onset (50+) Alcohol Use Disorder and Heavy Drinking

    DEFF Research Database (Denmark)

    Emiliussen, Jakob; Nielsen, Anette Søgaard; Andersen, Kjeld

    2017-01-01

    databases: MEDLINE, EMBASE, PubMed, and PsychInfo. Nine studies were included in the final review. Results: The search revealed that only very few studies have been conducted. Hence, the evidence is limited but suggests that stress, role/identity loss, and friends’approval of drinking are associated...... base their conclusions on a certain preconception of older adults with alcohol problems, which leads to a rowof circular arguments. The factors that have been measured seem to have changed over time. Conclusion: There has been a lack of focus on the field of late-onset AUD since the 1970s, which...

  9. Risk assessments for dating violence in mid to late adolescence and early adulthood.

    Science.gov (United States)

    Tapp, James; Moore, Estelle

    2016-10-01

    The objective of this paper is to review risk instruments that have been used in the assessment of the potential for violence within the dating relationships of young people. A review of the dating violence literature was conducted to identify risk assessment approaches that have been used to predict harmful behaviour within the dating relationships of people aged between 15 and 30 years. Risk assessments were evaluated on recommended quality criteria: predictive validity, accuracy (sensitivity and specificity) and inter-rater reliability. Only five studies describing assessments that focused specifically on dating violence risk factors were selected for review. Three assessments encompassed dating behaviours by victims that have been associated with an increased risk of further victimisation. Drawing on this evidence, we conclude that young people appear to be at greater risk of encountering dating violence if they have experienced violence in earlier attachment relationships; if their skills for coping with conflict and responding to coercion are limited and if the presence of peer influences reinforces offence supportive attitudes. The reliability and validity of existing intimate partner violence risk assessments that conceptually overlap with elements of dating violence risk warrant investigation to inform risk assessment developments in this field and, building on this, possible interventions to minimise future harm. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population

    Science.gov (United States)

    Hörnquist, Lina; Rickardsson, Jenny; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K.

    2015-01-01

    Background Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population. Methods The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982–2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. Results The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P type and a history of cranial radiation therapy were associated with outcomes. Conclusion An altered self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention. PMID:25332406

  11. Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population.

    Science.gov (United States)

    Hörnquist, Lina; Rickardsson, Jenny; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K

    2015-05-01

    Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population. The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982-2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified. The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Pathways from childhood intelligence and socioeconomic status to late-life cardiovascular disease risk.

    Science.gov (United States)

    Hagger-Johnson, Gareth; Mõttus, René; Craig, Leone C A; Starr, John M; Deary, Ian J

    2012-07-01

    C-reactive protein (CRP) is an acute-phase marker of systemic inflammation and considered an established risk marker for cardiovascular disease (CVD) in old age. Previous studies have suggested that low childhood intelligence, lower socioeconomic status (SES) in childhood or in later life, unhealthy behaviors, poor wellbeing, and high body mass index (BMI) are associated with inflammation. Life course models that simultaneously incorporate all these risk factors can explain how CVD risks accumulate over time, from childhood to old age. Using the data from 1,091 Scottish adults (Lothian Birth Cohort Study, 1936), a path model was constructed to predict CRP at age 70 from concurrent health behaviors, self-perceived quality of life, and BMI and adulthood SES as mediating variables, and from parental SES and childhood intelligence as distal risk factors. A well-fitting path model (CFI = .92, SRMR = .05) demonstrated significant indirect effects from childhood intelligence and parental social class to inflammation via BMI, health behaviors and quality of life (all ps intelligence, unhealthy behaviors, and higher BMI were also direct predictors of CRP. The life course model illustrated how CVD risks may accumulate over time, beginning in childhood and being both direct and transmitted indirectly via low adult SES, unhealthy behaviors, impaired quality of life, and high BMI. Knowledge on the childhood risk factors and their pathways to poor health can be used to identify high-risk individuals for more intensive and tailored behavior change interventions, and to develop effective public health policies.

  13. On the increased risk of developing late-onset epilepsy for patients with major affective disorder

    DEFF Research Database (Denmark)

    Nilsson, Flemming Mørkeberg; Kessing, Lars Vedel; Bolwig, Tom Gert

    2003-01-01

    for the control groups. However, the increased risk seemed to be due to the effect of comorbid alcohol or drug abuse and not to the effect of the affective illness itself. LIMITATIONS: The results only apply to hospitalised patients. Diagnoses are not validated for research purposes. CONCLUSION: Patients...... with a diagnosis of affective disorder have an increased risk of developing epilepsy in later life. In patients with affective disorder, comorbid alcoholism/drug abuse seriously increased the risk of a subsequent diagnosis of epilepsy....

  14. Perinatal Risks in "Late Motherhood" Defined Based On Parity and Preterm Birth Rate - an Analysis of the German Perinatal Survey (20th Communication).

    Science.gov (United States)

    Schure, V; Voigt, M; Schild, R L; Hesse, V; Carstensen, M; Schneider, K T M; Straube, S

    2012-01-01

    Aim: "Late motherhood" is associated with greater perinatal risks but the term lacks precise definition. We present an approach to determine what "late motherhood" associated with "high risk" is, based on parity and preterm birth rate. Materials and Methods: Using data from the German Perinatal Survey of 1998-2000 we analysed preterm birth rates in women with zero, one, or two previous live births. We compared groups of "late" mothers (with high preterm birth rates) with "control" groups of younger women (with relatively low preterm birth rates). Data of 208 342 women were analysed. For women with zero (one; two) previous live births, the "control" group included women aged 22-26 (27-31; 29-33) years. Women in the "late motherhood" group were aged > 33 (> 35; > 38) years. Results: The "late motherhood" groups defined in this way were also at higher risk of adverse perinatal events other than preterm birth. For women with zero (one; two) previous live births, normal cephalic presentation occurred in 89 % (92.7 %; 93.3 %) in the "control" group, but only in 84.5 % (90 %; 90.4 %) in the "late motherhood" group. The mode of delivery was spontaneous or at most requiring manual help in 71.3 % (83.4 %; 85.8 %) in the "control" group, but only in 51.4 % (72.2 %; 76.4 %) in the "late motherhood" group. Five-minute APGAR scores were likewise worse for neonates of "late" mothers and the proportion with a birth weight ≤ 2499 g was greater. Conclusion: "Late motherhood" that is associated with greater perinatal risks can be defined based on parity and preterm birth rate.

  15. Risk, Rationality and Nudging in Late Modern Society: Understanding the dynamics of the climate crisis

    OpenAIRE

    Jakobsen, Terne Sasha Thorn

    2016-01-01

    This study seeks to explore and explain how nudge theory may contribute to the understanding of thedynamics of the climate crisis in a ‘world risk society’. It is based on Ulrich Beck’s theory of a worldrisk society and unfolds through the combination of theories about risk, rationality and behaviour thatare ultimately brought together in relation to the climate crisis. A critical realistic perspective andmethod is taken to explore three hypothetical premises: 1) That the climate crisis is a ...

  16. Radioprotection of mouse CNS endothelial cells in vivo

    International Nuclear Information System (INIS)

    Lyubimova, N.; Coultas, P.; Martin, R.

    1996-01-01

    Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy γ-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

  17. XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

    Science.gov (United States)

    Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

    2014-03-01

    The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

  18. Late-onset neonatal sepsis, risk factors and interventions: an analysis of recurrent outbreaks of Serratia marcescens, 2006-2011.

    Science.gov (United States)

    Samuelsson, A; Isaksson, B; Hanberger, H; Olhager, E

    2014-01-01

    Between 2006 and 2011, 11 patients with Serratia marcescens sepsis and 47 patients colonized due to the spread of various clones were observed. These recurrent clusters brought about interventions to reduce spread between patients. To evaluate the effect of stepwise interventions to prevent S. marcescens colonization/sepsis and to analyse risk factors for late-onset sepsis (LOS). An open retrospective observational study was performed to evaluate the interventions. A retrospective case-control study was performed to analyse the risk factors for LOS. S. marcescens sepsis and colonization decreased after the stepwise adoption of hygiene interventions. Low gestational age, low birth weight, indwelling central venous or umbilical catheter, and ventilator treatment were identified as risk factors for LOS. Compliance with basic hygiene guidelines was the only intervention monitored continuously from late 2007. Compliance increased gradually to a steady high level in early 2009. There was a decrease in S. marcescens LOS, clustering after the second quarter of 2008. After the first quarter of 2009, S. marcescens colonization decreased. It was not possible to identify the specific effects of each intervention, but it is likely that an update of the hospital's antibiotic policy affected the occurrence of S. marcescens LOS. The delayed effect of interventions on S. marcescens colonization was probably due to the time it takes for new routines to have an effect, illustrated by the gradual increase in compliance with basic hygiene guidelines. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  19. Influence of childhood abuse and neglect subtypes on late-life suicide risk beyond depression.

    Science.gov (United States)

    Behr Gomes Jardim, Gabriel; Novelo, Marta; Spanemberg, Lucas; von Gunten, Armin; Engroff, Paula; Nogueira, Eduardo Lopes; Cataldo Neto, Alfredo

    2018-06-01

    The association of childhood maltreatment and suicide has been extensively examined within the population. Depression figures as a main cause for the elevated suicide rate in advanced ages and is often related to childhood maltreatment. The purpose of the present study was to examine the relationship between childhood maltreatment subtypes and suicide risk, testing geriatric depression as a moderator. This is a cross-sectional study looking at a sample of 449 individuals 60 year s old or older from the Multidimensional Study of the Elderly of Porto Alegre Family Health Strategy, Brazil (EMI-SUS/POA). Childhood maltreatment (Childhood Trauma Questionnaire), geriatric depressive symptoms (Geriatric Depression Scale), and suicide risk (Mini International Neuropsychiatric Interview) were assessed. The subtypes of childhood abuse and neglect were significantly associated with suicide risk. In the multivariate analysis, controlling for age, gender, income, marital status, ethnicity, smoking, and geriatric depression symptoms, all trauma subtypes remained associated with suicide risk with the exception of physical neglect (EA = 3.65; PA = 3.16; SA = 5.1; EN = 2.43; PN = 1.76). The present study showed that childhood maltreatment subtypes predicted suicide risk, and geriatric depression does not directly mediate this relation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Metallothionein expression and roles in the CNS

    DEFF Research Database (Denmark)

    Penkowa, Milena

    2002-01-01

      Metallothioneins (MTs) are low-molecular-weight (6-7 kDa) nonenzymatic proteins (60-68 amino acid residues, 25-30% being cysteine) expressed ubiquitous in the animal kingdom. In the central nervous system (CNS), three MT isoforms are known, namely MT-I to MT-III. MT-I and MT-II (MT...

  1. Optimizing the radiation therapy dose prescription for pediatric medulloblastoma: Minimizing the life years lost attributable to failure to control the disease and late complication risk

    DEFF Research Database (Denmark)

    Brodin, N. Patrik; Vogelius, Ivan R.; Bjork-Eriksson, Thomas

    2014-01-01

    Background. A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence...... is important, with 0.75 LYL (95% CI 0.60-7.2 years) for standard uniform 24 Gy CS irradiation. However, recurrence risk dominates the total LYL with 14.2 years (95% CI 13.4-16.6 years). Compared to standard treatment, a risk-adapted strategy prescribing 12 Gy to the spinal volume encompassing the 1st-10th......, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. Methods. Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling...

  2. The three-quarter power scaling of extinction risk in Late Pleistocene mammals, and a new theory of the size selectivity of extinction

    NARCIS (Netherlands)

    Polishchuk, L.

    2010-01-01

    Questions: What is the pattern of body mass versus extinction risk in the Late Pleistocene extinctions of mammals, both qualitatively and quantitatively? Are there patterns that relate extinction risk to the well-known allometries of body mass with population density or population growth rate?

  3. Surveillance of hepatic late adverse effects in a large cohort of long-term survivors of childhood cancer: prevalence and risk factors

    NARCIS (Netherlands)

    Mulder, Renée L.; Kremer, Leontien C. M.; Koot, Bart G. P.; Benninga, Marc A.; Knijnenburg, Sebastiaan L.; van der Pal, Helena J. H.; Koning, Caro C. E.; Oldenburger, Foppe; Wilde, James C. H.; Taminiau, Jan A. J. M.; Caron, Huib N.; van Dalen, Elvira C.

    2013-01-01

    Childhood cancer survivors (CCS) are a growing group of young individuals with a high risk of morbidity and mortality. We evaluated the prevalence and risk factors of hepatic late adverse effects, defined as elevated liver enzymes, in a large cohort of CCS. The cohort consisted of all five-year CCS

  4. The Importance of a Late First Trimester Placental Sonogram in Patients at Risk of Abnormal Placentation

    Directory of Open Access Journals (Sweden)

    Felipe Moretti

    2014-01-01

    Full Text Available Background. Placenta accreta is a potentially life-threatening obstetrical condition and is responsible for many emergency Caesarean hysterectomies. Early prenatal diagnosis may help minimize maternal morbidity and mortality. This report highlights risk factors, early diagnostic findings and complications associated with placenta accreta, and the role of first trimester sonography in diagnosis. Case. A 38-year-old pregnant woman, G2P1L1 with history of one previous Caesarean section, presented with vaginal bleeding at 13 weeks’ gestation. Ultrasound examination was highly suspicious of placenta previa with accreta. During an earlier 12-week scan for nuchal translucency measurement, the placenta was suboptimally visualized. She was counselled regarding potential maternal and fetal complications as well as management options. At 33 weeks’ gestation Caesarean hysterectomy was performed due to vaginal bleeding. Conclusion. Early ultrasound screening in high-risk patients may be advantageous in order to identify placenta accreta and conduct appropriate patient counseling regarding risks and management options.

  5. Spectrum of cancer risk late after AIDS onset in the United States.

    Science.gov (United States)

    Simard, Edgar P; Pfeiffer, Ruth M; Engels, Eric A

    2010-08-09

    Persons living with AIDS today remain at elevated cancer risk. Highly active antiretroviral therapy (HAART), widely available since 1996, prolongs life, but immune function is not fully restored. We conducted this study to assess long-term cancer risk among persons with AIDS relative to the general population and the impact of HAART on cancer incidence. Records of 263 254 adults and adolescents with AIDS (1980-2004) from 15 US regions were matched to cancer registries to capture incident cancers during years 3 through 5 and 6 through 10 after AIDS onset. Standardized incidence ratios (SIRs) were used to assess risks relative to the general population. Rate ratios (RRs) were used to compare cancer incidence before and after 1996 to assess the impact of availability of HAART. Risk was elevated for the 2 major AIDS-defining cancers: Kaposi sarcoma (SIRs, 5321 and 1347 in years 3-5 and 6-10, respectively) and non-Hodgkin lymphoma (SIRs, 32 and 15). Incidence of both malignancies declined in the HAART era (1996-2006). Risk was elevated for all non-AIDS-defining cancers combined (SIRs, 1.7 and 1.6 in years 3-5 and 6-10, respectively) and for the following specific non-AIDS-defining cancers: Hodgkin lymphoma and cancers of the oral cavity and/or pharynx, tongue, anus, liver, larynx, lung and/or bronchus, and penis. Anal cancer incidence increased between 1990-1995 and 1996-2006 (RR, 2.9; 95% confidence interval [CI], 2.1-4.0), as did that of Hodgkin lymphoma (RR, 2.0; 95% CI, 1.3-2.9). Among people who survived for several years or more after an AIDS diagnosis, we observed high risks of AIDS-defining cancers and increasing incidence of anal cancer and Hodgkin lymphoma.

  6. German register for detection of late sequelae after radiotherapy for children and adolescents (RiSK): present status and first results

    International Nuclear Information System (INIS)

    Boelling, T.; Schuck, A.; Willich, N.; Pape, H.; Ruebe, C.; Meyer, F.M.; Martini, C.; Timmermann, B.; Asadpour, B.; Kortmann, R.D.; Beck, J.D.; Langer, T.; Paulides, M.

    2007-01-01

    Undoubtedly, radiotherapy is an important treatment strategy for many malignancies in paediatric oncology. However, sufficient data about late side effects do not exist. There is a lack of information about radiation dose-effect relationships in view of late side effects in childhood and adolescence. Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Many of these analyses are limited due to little information about organ dose levels and older radiation techniques in some cases. Therefore the German Group of Paediatric Radiation Oncology (APRO) established the ''Register for the evaluation of late side effects after radiation in childhood and adolescence (RiSK)''. Aim of this prospective multicentric register study is to evaluate irradiation dose effect relationships of organs and part of organs with respect to late effects. The feasibility of RiSK has already been shown and first results have recently been published. The characterization of late effects after cancer therapy in childhood is of rising interest. In Germany, several study groups like the ''Late Effects Surveillance System'' (LESS) or the working group ''Quality of life'' examine different aspects of late effects. In the United States of America, the ''Childhood Cancer Survivor Study'' has been established to characterize retrospectively the health status of 5-year-survivors of childhood cancer. In these studies, more than 12,000 patients were evaluated by questionnaires regarding their health status. For radiotherapy, this study is not able to give detailed information about late side effects due to rare data about radiation doses and organ dose levels. To our knowledge, ''RiSK'' is the only multicentric study that evaluates radiation associated side effects prospectively with detailed information about organ dose levels. (orig.)

  7. Prenatal exposure to vitamin D from fortified margarine and risk of fractures in late childhood

    DEFF Research Database (Denmark)

    Händel, Mina Nicole; Frederiksen, Peder; Osmond, Clive

    2017-01-01

    Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification programme, we examined the risk of fractures among 10-18-year-old children from proximate birth cohorts born around the date of the termination of the programme. For all subjec...

  8. Liver stiffness value-based risk estimation of late recurrence after curative resection of hepatocellular carcinoma: development and validation of a predictive model.

    Directory of Open Access Journals (Sweden)

    Kyu Sik Jung

    Full Text Available Preoperative liver stiffness (LS measurement using transient elastography (TE is useful for predicting late recurrence after curative resection of hepatocellular carcinoma (HCC. We developed and validated a novel LS value-based predictive model for late recurrence of HCC.Patients who were due to undergo curative resection of HCC between August 2006 and January 2010 were prospectively enrolled and TE was performed prior to operations by study protocol. The predictive model of late recurrence was constructed based on a multiple logistic regression model. Discrimination and calibration were used to validate the model.Among a total of 139 patients who were finally analyzed, late recurrence occurred in 44 patients, with a median follow-up of 24.5 months (range, 12.4-68.1. We developed a predictive model for late recurrence of HCC using LS value, activity grade II-III, presence of multiple tumors, and indocyanine green retention rate at 15 min (ICG R15, which showed fairly good discrimination capability with an area under the receiver operating characteristic curve (AUROC of 0.724 (95% confidence intervals [CIs], 0.632-0.816. In the validation, using a bootstrap method to assess discrimination, the AUROC remained largely unchanged between iterations, with an average AUROC of 0.722 (95% CIs, 0.718-0.724. When we plotted a calibration chart for predicted and observed risk of late recurrence, the predicted risk of late recurrence correlated well with observed risk, with a correlation coefficient of 0.873 (P<0.001.A simple LS value-based predictive model could estimate the risk of late recurrence in patients who underwent curative resection of HCC.

  9. Risk factors for tube exposure as a late complication of glaucoma drainage implant surgery

    Directory of Open Access Journals (Sweden)

    Chaku M

    2016-03-01

    Full Text Available Meenakshi Chaku,1 Peter A Netland,2 Kyoko Ishida,3 Douglas J Rhee4 1Department of Ophthalmology, Loyola University Chicago, Maywood, IL, 2Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville, VA, USA; 3Department of Ophthalmology, Toho University, Tokyo, Japan; 4Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USA Purpose: The purpose of this study was to evaluate the risk factors for tube exposure after glaucoma drainage implant surgery.Patients and methods: This was a retrospective case-controlled observational study of 64 eyes from 64 patients. Thirty-two eyes of 32 patients with tube erosion requiring surgical revision were compared with 32 matched control eyes of 32 patients. Univariate and multivariate risk factor analyses were performed.Results: Mean age was significantly younger in the tube exposure group compared with the control group (48.2±28.1 years versus 67.3±18.0 years, respectively; P=0.003. The proportion of diabetic patients (12.5% in the tube exposure group was significantly less (P=0.041 compared with the control group (37.5%. Comparisons of the type and position of the drainage implant were not significantly different between the two groups. The average time to tube exposure was 17.2±18.0 months after implantation of the drainage device. In both univariate and multivariate analyses, younger age (P=0.005 and P=0.027 and inflammation prior to tube exposure (P≤0.001 and P=0.004 were significant risk factors. Diabetes was a significant risk factor only in the univariate analysis (P=0.027.Conclusion: Younger age and inflammation were significant risk factors for tube exposure after drainage implant surgery. Keywords: glaucoma drainage implant complications, Ahmed Glaucoma Valve, Baerveldt implant, tube erosion, pericardial patch graft

  10. Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

    Directory of Open Access Journals (Sweden)

    David Thomson

    2012-01-01

    Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

  11. Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia.

    Science.gov (United States)

    Tolppanen, Anna-Maija; Solomon, Alina; Kulmala, Jenni; Kåreholt, Ingemar; Ngandu, Tiia; Rusanen, Minna; Laatikainen, Tiina; Soininen, Hilkka; Kivipelto, Miia

    2015-04-01

    Physical activity may be beneficial for cognition, but the effect may vary depending on personal characteristics. We investigated the associations between leisure-time physical activity (LTPA) from mid- to late life, the risk of dementia, and the role of body mass index, sex, and APOE in the CAIDE study during 28-year follow-up. Cognitive function of a random subsample was assessed at a mean age of 78.8 years (n = 1511), and dementia/Alzheimer's disease (AD) diagnoses were identified from national registers for the entire target population (n = 3559). Moderate (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.08-1.99) and low levels of midlife LTPA (HR, 1.39; 95% CI, 0.99-1.95) were associated with higher risk of dementia in comparison with the most active category. The benefits were more pronounced among men, overweight individuals, and APOE ε4 noncarriers. Maintaining high LTPA (HR, 0.16; 95% CI, 0.06-0.41) or increasing LTPA (HR, 0.19; 95% CI, 0.09-0.40) after midlife was associated with lower dementia risk. Similar results were observed for AD. The window of opportunity for preventive physical activity interventions may extend from midlife to older ages. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  12. Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

    Science.gov (United States)

    Willette, Auriel A; Bendlin, Barbara B; Starks, Erika J; Birdsill, Alex C; Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C; La Rue, Asenath; Hermann, Bruce P; Koscik, Rebecca L; Jonaitis, Erin M; Sager, Mark A; Asthana, Sanjay

    2015-09-01

    Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake. Regional glucose uptake determined using FDG-PET and neuropsychological factors. Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P factor scores. Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism

  13. Risk factors associated with cognitions for late-onset depression based on anterior and posterior default mode sub-networks.

    Science.gov (United States)

    Liu, Rui; Yue, Yingying; Hou, Zhenghua; Yuan, Yonggui; Wang, Qiao

    2018-08-01

    Abnormal functional connectivity (FC) in the default mode network (DMN) plays an important role in late-onset depression (LOD) patients. In this study, the risk predictors of LOD based on anterior and posterior DMN are explored. A total of 27 LOD patients and 40 healthy controls (HC) underwent resting-state functional magnetic resonance imaging and cognitive assessments. Firstly, FCs within DMN sub-networks were determined by placing seeds in the ventral medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Secondly, multivariable logistic regression was used to identify risk factors for LOD patients. Finally, correlation analysis was performed to investigate the relationship between risk factors and the cognitive value. Multivariable logistic regression showed that the FCs between the vmPFC and right middle temporal gyrus (MTG) (vmPFC-MTG_R), FCs between the vmPFC and left precuneus (PCu), and FCs between the PCC and left PCu (PCC-PCu_L) were the risk factors for LOD. Furthermore, FCs of the vmPFC-MTG_R and PCC-PCu_L correlated with processing speed (R = 0.35, P = 0.002; R = 0.32, P = 0.009), and FCs of the vmPFC-MTG_R correlated with semantic memory (R = 0.41, P = 0.001). The study was a cross-sectional study. The results may be potentially biased because of a small sample. In this study, we confirmed that LOD patients mainly present cognitive deficits in processing speed and semantic memory. Moreover, our findings further suggested that FCs within DMN sub-networks associated with cognitions were risk factors, which may be used for the prediction of LOD. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Screening of Early and Late Onset Alzheimer's Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy.

    Science.gov (United States)

    Ferrari, Raffaele; Ferrara, Michela; Alinani, Anwar; Sutton, Roger Brian; Famà, Francesco; Picco, Agnese; Rodriguez, Guido; Nobili, Flavio; Momeni, Parastoo

    2015-01-01

    Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer's disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer's and non-Alzheimer's forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalence of AD in the female population compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area. 

  15. CNS penetration of ART in HIV-infected children

    NARCIS (Netherlands)

    van den Hof, Malon; Blokhuis, Charlotte; Cohen, Sophie; Scherpbier, Henriette J.; Wit, Ferdinand W. N. M.; Pistorius, M. C. M.; Kootstra, Neeltje A.; Teunissen, Charlotte E.; Mathot, Ron A. A.; Pajkrt, Dasja

    2018-01-01

    Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce. Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Patients and methods: Antiretroviral drug levels were measured in paired

  16. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families.

    Directory of Open Access Journals (Sweden)

    Carlos Cruchaga

    Full Text Available Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD. Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7% carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09 × 10⁻⁵; OR = 2.21; 95%CI = 1.49-3.28 or an unselected population of 12,481 samples (p = 6.82 × 10⁻⁵; OR = 2.19; 95%CI = 1.347-3.26. Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early-onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS.

  17. Cancers of the Brain and CNS: Global Patterns and Trends in Incidence.

    Science.gov (United States)

    Mortazavi, S M J; Mortazavi, S A R; Paknahad, M

    2018-03-01

    Miranda-Filho et al. in their recently published paper entitled "Cancers of the brain and CNS: global patterns and trends in incidence" provided a global status report of the geographic and temporal variations in the incidence of brain and CNS cancers in different countries across continents worldwide. While the authors confirm the role of genetic risk factors and ionizing radiation exposures, they claimed that no firm conclusion could be drawn about the role of exposure to non-ionizing radiation. The paper authored by Miranda-Filho et al. not only addresses a challenging issue, it can be considered as a good contribution in the field of brain and CNS cancers. However, our correspondence addresses a basic shortcoming of this paper about the role of electromagnetic fields and cancers and provides evidence showing that exposure to radiofrequency electromagnetic fields (RF-EMFs), at least at high levels and long durations, can increases the risk of cancer.

  18. Carotid endarterectomy in patients with occlusion of the contralateral carotid artery. Perioperative risk and late results

    DEFF Research Database (Denmark)

    Sillesen, H; Schroeder, T; Rasmussen, L

    1987-01-01

    severe strokes when compared to patients with only minor reduction in CPP. In addition, the internal carotid artery blood flow following endarterectomy was significantly higher in the low pressure group (P less than 0.02). No patients were lost during follow-up, for a mean of 34 months. The cumulative....... Compared with a complication rate of about 5% previously reported from this institution, this clearly indicates contralateral carotid occlusion as a major risk factor in carotid surgery. Though not statistically significant, patients with severely reduced cerebral perfusion pressure (CPP) had suffered more...

  19. Risk assessment and late effects of radiation in low-earth orbits

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1989-01-01

    The radiation dose rates in low-earth orbits are dependent on the altitude and orbital inclination. The doses to which the crews of space vehicles are exposed is governed by the duration of the mission and the shielding, and in low-earth orbit missions protons are the dominant particles encountered. The risk of concern with the low dose rates and the relatively low total doses of radiation that will be incurred on the space station is excess cancer. The National Council on Radiation Protection and Measurements has recently recommended career dose-equivalent limits that take into account sex and age. The new recommendations for career limits range from 1.0 Sv to 4 Sv, depending on sex and on the age at the time of their first space mission, compared to a single career limit of 4.0 Sv previously used by NASA. Risk estimates for radiated-induced cancer are evolving and changes in the current guidance may be required in the next few years. 10 refs., 1 fig., 3 tabs

  20. Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance.

    Science.gov (United States)

    Skinner, Roderick

    2018-02-01

    Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors. These cause a wide range of chronic glomerular and tubular toxicities, often with potentially severe clinical sequelae. Many risk factors for developing nephrotoxicity, mostly patient and treatment related, have been described, but we remain unable to predict all episodes of renal damage. This implies that other factors may be involved, such as genetic polymorphisms influencing drug metabolism. Although our knowledge of the long-term outcomes of chronic nephrotoxicity is increasing, there is still much to learn, including how we can optimally predict or achieve early detection of nephrotoxicity. Greater understanding of the pathogenesis of nephrotoxicity is needed before its occurrence can be prevented.

  1. Prenatal exposure to vitamin D from fortified margarine and risk of fractures in late childhood

    DEFF Research Database (Denmark)

    Händel, Mina Nicole; Frederiksen, Peder; Osmond, Clive

    2017-01-01

    Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification programme, we examined the risk of fractures among 10–18-year-old children from proximate birth cohorts born around the date of the termination of the programme. For all subjects...... in fracture rates across birth cohorts was analysed by fitting an age-cohort model to the data. We addressed the potential modification of the effect of vitamin D availability by season of birth. The risk of fractures was increased among both girls and boys who were born before the vitamin D fortification...... terminated in 1985 (rate ratio (RR) exposed v. non-exposed girls: 1·15 (95 % CI 1·11, 1·20); RR exposed v. non-exposed boys: 1·11 (95 % CI 1·07, 1·14). However, these associations no longer persisted after including the period effects. There was no interaction between season of birth and vitamin D...

  2. CNS adverse events associated with antimalarial agents. Fact or fiction?

    NARCIS (Netherlands)

    Phillips-Howard, P. A.; ter Kuile, F. O.

    1995-01-01

    CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too

  3. Endovascular transplantation of stem cells to the injured rat CNS

    International Nuclear Information System (INIS)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan; Le Blanc, Katarina

    2009-01-01

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  4. Endovascular transplantation of stem cells to the injured rat CNS

    Energy Technology Data Exchange (ETDEWEB)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

    2009-10-15

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  5. CNS effects following the treatment of malignancy

    International Nuclear Information System (INIS)

    Rane, N.; Quaghebeur, G.

    2012-01-01

    Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes.

  6. Therapeutic potential of agmatine for CNS disorders.

    Science.gov (United States)

    Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

    2017-09-01

    Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  8. Cerebral blood flow variations in CNS lupus

    International Nuclear Information System (INIS)

    Kushner, M.J.; Tobin, M.; Fazekas, F.; Chawluk, J.; Jamieson, D.; Freundlich, B.; Grenell, S.; Freemen, L.; Reivich, M.

    1990-01-01

    We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery

  9. Statins Reduces the Risk of Dementia in Patients with Late-Onset Depression: A Retrospective Cohort Study.

    Science.gov (United States)

    Yang, Ya-Hsu; Teng, Hao-Wei; Lai, Yen-Ting; Li, Szu-Yuan; Lin, Chih-Ching; Yang, Albert C; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Hsu, Fu-Ying; Liu, Chih-Kuang; Liu, Wen-Sheng

    2015-01-01

    Patients with late-onset depression (LOD) have been reported to run a higher risk of subsequent dementia. The present study was conducted to assess whether statins can reduce the risk of dementia in these patients. We used the data from National Health Insurance of Taiwan during 1996-2009. Standardized Incidence Ratios (SIRs) were calculated for LOD and subsequent dementia. The criteria for LOD diagnoses included age ≥65 years, diagnosis of depression after 65 years of age, at least three service claims, and treatment with antidepressants. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients for validation studies. Kaplan-Meier curve estimate was used to measure the group of patients with dementia living after diagnosis of LOD. Totally 45,973 patients aged ≥65 years were enrolled. The prevalence of LOD was 12.9% (5,952/45,973). Patients with LOD showed to have a higher incidence of subsequent dementia compared with those without LOD (Odds Ratio: 2.785; 95% CI 2.619-2.958). Among patients with LOD, lipid lowering agent (LLA) users (for at least 3 months) had lower incidence of subsequent dementia than non-users (Hazard Ratio = 0.781, 95% CI 0.685-0.891). Nevertheless, only statins users showed to have reduced risk of dementia (Hazard Ratio = 0.674, 95% CI 0.547-0.832) while other LLAs did not, which was further validated by Kaplan-Meier estimates after we used the propensity scores with the one-to-one nearest-neighbor matching model to control the confounding factors. Statins may reduce the risk of subsequent dementia in patients with LOD.

  10. Risk and resilience in the late glacial: A case study from the western Mediterranean

    Science.gov (United States)

    Barton, C. Michael; Aura Tortosa, J. Emili; Garcia-Puchol, Oreto; Riel-Salvatore, Julien G.; Gauthier, Nicolas; Vadillo Conesa, Margarita; Pothier Bouchard, Geneviève

    2018-03-01

    The period spanning the Last Glacial Maximum through early Holocene encompasses dramatic and rapid environmental changes that offered both increased risk and new opportunities to human populations of the Mediterranean zone. The regional effects of global climate change varied spatially with latitude, topography, and distance from a shifting coastline; and human adaptations to these changes played out at these regional scales. To better understand the spatial and temporal dynamics of climate change and human social-ecological-technological systems (or SETS) during the transition from full glacial to interglacial, we carried out a meta-analysis of archaeological and paleoenvironmental datasets across the western Mediterranean region. We compiled information on prehistoric technology, land-use, and hunting strategies from 291 archaeological assemblages, recovered from 122 sites extending from southern Spain, through Mediterranean France, to northern and peninsular Italy, as well as 2,386 radiocarbon dates from across this region. We combine these data on human ecological dynamics with paleoenvironmental information derived from global climate models, proxy data, and estimates of coastlines modeled from sea level estimates and digital terrain. The LGM represents an ecologically predictable period for over much of the western Mediterranean, while the remainder of the Pleistocene was increasingly unpredictable, making it a period of increased ecological risk for hunter-gatherers. In response to increasing spatial and temporal uncertainty, hunter-gatherers reorganized different constituents of their SETS, allowing regional populations to adapt to these conditions up to a point. Beyond this threshold, rapid environmental change resulted in significant demographic change in Mediterranean hunter-gatherer populations.

  11. Treatment options for Primary CNS Lymphoma.

    Science.gov (United States)

    Laghari, Altaf Ali; Ahmed, Syed Ijlal; Jabbar, Adnan; Shamim, Muhammad Shahzad

    2018-03-01

    Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.

  12. Engineering progress of CNS concept in Hanaro

    International Nuclear Information System (INIS)

    Choi, C.O.; Park, K.N.; Park, S.H.

    1997-01-01

    The Korea Atomic Energy research Institute (KAERI) strives to provide utilizing facilities on and around the Hanaro reactor in order to activate advanced researches by neutron application. As one of the facilities to be installed, the conceptual design work of CNS was started in 1996 with a project schedule of 5 years so that its installation work can be finished by the year 2000. And the major engineering targets of this CNS facility are established for a minimum physical interference with the present facilities of the Hanaro, a reach-out of very-high-gain factors in the cold neutron flux, a simplicity of the maintenance of the facility, and a safety in the operation of the facility as well as the reactor. For the conceptual design of Hanaro CNS, the experience of utilization and production of cold neutron at WWR-M reactor Gatchina, Russia has been used with that of elaborations for PIK reactor in design for neutron guide systems and instruments. (author)

  13. Risk estimates for meningiomas and other late effects after diagnostic X-ray exposure of the skull

    International Nuclear Information System (INIS)

    Pflugbeil, S.; Pflugbeil, C.; Schmitz-Feuerhake, I.

    2011-01-01

    This study aims to investigate the contribution of diagnostic exposures to the rising rates of brain tumours and other neoplasms which are observed in several industrial nations. Included are benign tumours in the head and neck region and cataracts which are neglected in usual risk estimates by international and national radiation protection committees. Dose-effect relationships for tumours of the brain, skin, thyroid and other sites of the head region, leukaemia and cataracts are taken from the literature. Risk estimates are derived for paediatric head computed tomographies (CTs) as well as for brain tumours in adults. On the basis of estimates for Germany about the number of head scans, the annual rate of radiation-induced diseases is calculated. About 1000 annual paediatric CT investigations of the skull will lead to about three excess neoplasms in the head region, i.e. the probability of an induced late effect must be suspected in the range of some thousands. Additionally, a relevant increase of cataracts must be considered. The radiation-induced occurrence of meningiomas and other brain tumours most probably contributes to the continuously increasing incidence of these diseases which is observed in several industrial nations, as well as the exposure of the bone marrow by CT to the increase of childhood leukaemia. (authors)

  14. Risk of somatic late effects in man following incorporation of 224Ra(thorium X)

    International Nuclear Information System (INIS)

    Wick, R.R.; Chmelevsky, D.

    1986-03-01

    1568 ankylosing spondylitis patients, injected with repeated injections of 224 Ra for treatment of their disease, have been observed in the GSF (study II). By the end of 1985 3 cases of malignant tumours in the skeleton had been observed, compared to 0 cases in a control group. According to the cancer mortality statistics for the FRG the age-corrected number of spontaneous bone tumours expected would be 0.4-0.7. In contrast, a recent risk estimate from the data of the patient group of study I (SPIESS/MAYS) who were treated with considerably higher doses, suggests an expected number of 5.8 radiation induced bone tumours for the present follow-up time. Latest observations from that group show that bone tumours may occur up to 33 yr after treatment with 224 Ra. Thus, the possibility of additional cases of bone tumours occurring in study II cannot be excluded. One striking observation was that 2 of the 3 skeletal tumours observed in study II were tumours of the bone marrow; there has been only 1 bone marrow tumour in the high dose group (study I) among 56 bone tumours. In addition there have been 6 and 5 leukaemias in the exposure and control group respectively. Of the 6 leukaemias in the exposure group 3 were chronic myeloid leukaemias (CML), whereas among the 5 leukaemias in the control group there was no CML. (orig./MG) [de

  15. Going to sleep in the supine position is a modifiable risk factor for late pregnancy stillbirth; Findings from the New Zealand multicentre stillbirth case-control study.

    Directory of Open Access Journals (Sweden)

    Lesley M E McCowan

    Full Text Available Our objective was to test the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation.A multicentre case-control study was conducted in seven New Zealand health regions, between February 2012 and December 2015. Cases (n = 164 were women with singleton pregnancies and late stillbirth, without congenital abnormality. Controls (n = 569 were women with on-going singleton pregnancies, randomly selected and frequency matched for health region and gestation. The primary outcome was adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night. The last night was the night before the late stillbirth was thought to have occurred or the night before interview for controls. Going-to-sleep position on the last night was categorised as: supine, left-side, right-side, propped or restless. Multivariable logistic regression adjusted for known confounders.Supine going-to-sleep position on the last night was associated with increased late stillbirth risk (adjusted odds ratios (aOR 3.67, 95% confidence interval (CI 1.74 to 7.78 with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth (aOR, 95% CI were: BMI (1.04, 1.01 to 1.08 per unit, maternal age ≥40 (2.88, 1.31 to 6.32, birthweight <10th customised centile (2.76, 1.59 to 4.80, and <6 hours sleep on the last night (1.81, 1.14 to 2.88. The risk associated with supine-going-to-sleep position was greater for term (aOR 10.26, 3.00 to 35.04 than preterm stillbirths (aOR 3.12, 0.97 to 10.05.Supine going-to-sleep position is associated with a 3.7 fold increase in overall late stillbirth risk, independent of other common risk factors. A public health campaign encouraging women not to go-to-sleep supine in the third trimester has potential to reduce late stillbirth by approximately 9%.

  16. Prophylactic CNS therapy in childhood leukemia

    International Nuclear Information System (INIS)

    Yokoyama, Takashi; Hiyoshi, Yasuhiko; Fujimoto, Takeo

    1982-01-01

    This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm 3 ) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm 3 ) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m 2 ) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m 2 , the CSF concentration of MTX rose to 2.3 +- 2.4 x 10 -6 M after initiation of infusion and remained in 10 -7 M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% i n Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC. (author)

  17. Perinatal Risks in “Late Motherhood” Defined Based On Parity and Preterm Birth Rate – an Analysis of the German Perinatal Survey (20th Communication)

    Science.gov (United States)

    Schure, V.; Voigt, M.; Schild, R. L.; Hesse, V.; Carstensen, M.; Schneider, K. T. M.; Straube, S.

    2012-01-01

    Aim: “Late motherhood” is associated with greater perinatal risks but the term lacks precise definition. We present an approach to determine what “late motherhood” associated with “high risk” is, based on parity and preterm birth rate. Materials and Methods: Using data from the German Perinatal Survey of 1998–2000 we analysed preterm birth rates in women with zero, one, or two previous live births. We compared groups of “late” mothers (with high preterm birth rates) with “control” groups of younger women (with relatively low preterm birth rates). Data of 208 342 women were analysed. For women with zero (one; two) previous live births, the “control” group included women aged 22–26 (27–31; 29–33) years. Women in the “late motherhood” group were aged > 33 (> 35; > 38) years. Results: The “late motherhood” groups defined in this way were also at higher risk of adverse perinatal events other than preterm birth. For women with zero (one; two) previous live births, normal cephalic presentation occurred in 89 % (92.7 %; 93.3 %) in the “control” group, but only in 84.5 % (90 %; 90.4 %) in the “late motherhood” group. The mode of delivery was spontaneous or at most requiring manual help in 71.3 % (83.4 %; 85.8 %) in the “control” group, but only in 51.4 % (72.2 %; 76.4 %) in the “late motherhood” group. Five-minute APGAR scores were likewise worse for neonates of “late” mothers and the proportion with a birth weight ≤ 2499 g was greater. Conclusion: “Late motherhood” that is associated with greater perinatal risks can be defined based on parity and preterm birth rate. PMID:25253904

  18. German register for detection of late sequelae after radiotherapy for children and adolescents (RiSK): present status and first results

    Energy Technology Data Exchange (ETDEWEB)

    Boelling, T.; Schuck, A.; Willich, N. [Dept. of Radiotherapy of the Univ. Hospital Muenster (Germany); Pape, H. [Dept. of Radiotherapy of the Univ. Hospital Duesseldorf (Germany); Ruebe, C. [Dept. of Radiotherapy of the Univ. Saarland, Homburg/Saar (Germany); Meyer, F.M. [Dept. of Radiotherapy of the Clinic of Augsburg (Germany); Martini, C. [Dept. of Radiotherapy of the Univ. Hospitals Freiburg (Germany); Timmermann, B. [Paul Scherrer Inst., Villigen (Switzerland); Asadpour, B. [Dept. of Radiotherapy of the Univ. Hospital Aachen (Germany); Kortmann, R.D. [Dept. of Radiotherapy of the Univ. Hospital Leipzig (Germany); Beck, J.D.; Langer, T.; Paulides, M. [LESS Center, Univ. Children' s Hospital Erlangen (Germany)

    2007-12-15

    Undoubtedly, radiotherapy is an important treatment strategy for many malignancies in paediatric oncology. However, sufficient data about late side effects do not exist. There is a lack of information about radiation dose-effect relationships in view of late side effects in childhood and adolescence. Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Many of these analyses are limited due to little information about organ dose levels and older radiation techniques in some cases. Therefore the German Group of Paediatric Radiation Oncology (APRO) established the 'Register for the evaluation of late side effects after radiation in childhood and adolescence (RiSK)'. Aim of this prospective multicentric register study is to evaluate irradiation dose effect relationships of organs and part of organs with respect to late effects. The feasibility of RiSK has already been shown and first results have recently been published. The characterization of late effects after cancer therapy in childhood is of rising interest. In Germany, several study groups like the 'Late Effects Surveillance System' (LESS) or the working group 'Quality of life' examine different aspects of late effects. In the United States of America, the 'Childhood Cancer Survivor Study' has been established to characterize retrospectively the health status of 5-year-survivors of childhood cancer. In these studies, more than 12,000 patients were evaluated by questionnaires regarding their health status. For radiotherapy, this study is not able to give detailed information about late side effects due to rare data about radiation doses and organ dose levels. To our knowledge, 'RiSK' is the only multicentric study that evaluates radiation associated side effects prospectively with detailed information about organ dose levels. (orig.)

  19. Gender Differences in Internalizing Symptoms and Suicide Risk Among Men and Women Seeking Treatment for Cannabis Use Disorder from Late Adolescence to Middle Adulthood.

    Science.gov (United States)

    Foster, Katherine T; Li, Ningfei; McClure, Erin A; Sonne, Susan C; Gray, Kevin M

    2016-07-01

    Cannabis continues to rise in popularity as the perception of its harmfulness decreases and evidence of its deleterious developmental effect increases. While internalizing distress and suicide risk have been linked with cannabis use problems [DSM-5 cannabis use disorder (CUD); DSM-IV cannabis abuse and dependence] it remains unclear how this association varies over the course of development in treatment-seeking men and women. The current study utilized the National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) to conduct a cross-sectional comparison of internalizing distress and suicide risk among men (n=437) and women (n=163) spanning ages 18-50 who met DSM-5 criteria for CUD. Interactions between gender and developmental stage (i.e., late adolescence, early adulthood, and middle adulthood) were observed for suicide risk and anxiety but not depression problems. Specifically, women seeking CUD treatment in late adolescence and middle adulthood exhibited significantly higher rates of anxiety and suicide risk compared to men seeking treatment during the same developmental stages. Internalizing distress and suicide risk did not differ between treatment-seeking men and women in the early adult stage. Overall, results suggest that the structure of risk for CUD may differ in men and women across the lifespan and that women presenting for CUD treatment during late adolescence and middle adulthood may uniquely benefit from intervention designed to address these elevations in anxiety and suicide risk. Published by Elsevier Inc.

  20. Central Nervous System (CNS Disease Triggering Takotsubo Syndrome

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2016-01-01

    Full Text Available Takotsubo syndrome (TTS is usually triggered by psychological or physical stress. One of the many physical sources of stress are central nervous system (CNS disorders. CNS disorders most frequently triggering TTS include subarachnoid bleeding, epilepsy, ischemic stroke, migraine, and intracerebral bleeding. More rare CNS-triggers of TTS include posterior reversible encephalopathy syndrome (PRES, amyotrophic lateral sclerosis, encephalitis, or traumatic brain or spinal cord injury. TTS triggered by any of the CNS disorders needs to be recognized since adequate treatment of TTS may improve the general outcome from the CNS disorder as well. Neurologists need to be aware of TTS as a complication of specific CNS disorders but TTS may be triggered also by CNS disorders so far not recognised as causes of TTS.

  1. SINS/CNS Nonlinear Integrated Navigation Algorithm for Hypersonic Vehicle

    Directory of Open Access Journals (Sweden)

    Yong-jun Yu

    2015-01-01

    Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.

  2. The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Villa, Diego; Michaelsen, Thomas Yssing

    2017-01-01

    Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknow...

  3. A Latent Transition Analysis of English Learners with Reading Disabilities: Do Measures of Cognition Add to Predictions of Late Emerging Risk Status?

    Science.gov (United States)

    Swanson, H. Lee

    2017-01-01

    The purpose of this cohort sequential study was to extend previously reported latent transition analyses conducted by Swanson, Kudo, and Guzman-Orth (2016) by determining the role of cognitive measures in identifying English learners (EL) at risk for late emerging reading disabilities (LERD). To this end, EL students (N = 450) in Grades 1, 2, and…

  4. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  5. Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-07-01

    The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

  6. Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

    International Nuclear Information System (INIS)

    2015-01-01

    The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

  7. Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

    Science.gov (United States)

    Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

    2013-12-01

    Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Dynamics of rectal balloon implant shrinkage in prostate VMAT. Influence on anorectal dose and late rectal complication risk

    Energy Technology Data Exchange (ETDEWEB)

    Vanneste, Ben G.L.; Wijk, Y. van; Lutgens, L.C.; Limbergen, E.J. van; Lambin, P. [Maastricht University Medical Center+, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Lin, E.N. van [Radiotherapy Bonn-Rhein-Sieg, Troisdorf (Germany); Beek, K. van de [Maastricht University Medical Center+, Department of Urology, Maastricht (Netherlands); Hoffmann, A.L. [Maastricht University Medical Center+, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology - OncoRay, Dresden (Germany); University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy, Dresden (Germany)

    2018-01-15

    To assess the effect of a shrinking rectal balloon implant (RBI) on the anorectal dose and complication risk during the course of moderately hypofractionated prostate radiotherapy. In 15 patients with localized prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and prostate-rectum separation. The absolute anorectal volume encompassed by the 2 Gy equieffective 75 Gy isodose (V{sub 75Gy}) was recalculated as well as the mean anorectal dose. The increase in estimated risk of grade 2-3 late rectal bleeding (LRB) between the start and end of treatment was predicted using nomograms. The observed acute and late toxicities were evaluated. A significant shrinkage of RBI volumes was observed, with an average volume of 70.4% of baseline at the end of the treatment. Although the prostate-rectum separation significantly decreased over time, it remained at least 1 cm. No significant increase in V{sub 75Gy} of the anorectum was observed, except in one patient whose RBI had completely deflated in the third week of treatment. No correlation between mean anorectal dose and balloon deflation was found. The increase in predicted LRB risk was not significant, except in the one patient whose RBI completely deflated. The observed toxicities confirmed these findings. Despite significant decrease in RBI volume the high-dose rectal volume and the predicted LRB risk were unaffected due to a persistent spacing between the prostate and the anterior rectal wall. (orig.) [German] Beurteilung der Wirkung eines schrumpfenden rektalen Ballonimplantats (RBI) auf die anorektale Dosis und das Komplikationsrisiko im Verlauf einer maessig hypofraktionierten Strahlentherapie der Prostata. Ein RBI wurde 15 Patienten mit lokal begrenztem Prostatakarzinom implantiert. Zur Messung der Dynamik des RBI-Volumens und der Prostata-Rektum-Trennung wurde eine woechentliche Kilovolt-Cone-beam-Computertomographie (CBCT

  9. Cognitive behavioral therapy vs. Tai Chi for late life insomnia and inflammatory risk: a randomized controlled comparative efficacy trial.

    Science.gov (United States)

    Irwin, Michael R; Olmstead, Richard; Carrillo, Carmen; Sadeghi, Nina; Breen, Elizabeth C; Witarama, Tuff; Yokomizo, Megumi; Lavretsky, Helen; Carroll, Judith E; Motivala, Sarosh J; Bootzin, Richard; Nicassio, Perry

    2014-09-01

    To investigate the comparative efficacy of cognitive behavioral therapy (CBT), Tai Chi Chih (TCC), and sleep seminar education control (SS) on the primary outcome of insomnia diagnosis, and secondary outcomes of sleep quality, fatigue, depressive symptoms, and inflammation in older adults with insomnia. Randomized controlled, comparative efficacy trial. Los Angeles community. 123 older adults with chronic and primary insomnia. Random assignment to CBT, TCC, or SS for 2-hour group sessions weekly over 4 months with follow-up at 7 and 16 months. Insomnia diagnosis, patient-reported outcomes, polysomnography (PSG), and high-sensitivity C-reactive protein (CRP) levels. CBT performed better than TCC and SS in remission of clinical insomnia as ascertained by a clinician (P 3.0 mg/L) at 16 months (odds ratio [OR], 0.26 [95% CI, 0.07-0.97] P insomnia was associated with lower levels of CRP (P insomnia remission. PSG measures did not change. Treatment of late-life insomnia is better achieved and sustained by cognitive behavioral therapies. Insomnia treatment and remission reduces a marker of inflammatory risk, which has implications for cardiovascular morbidity and diabetes observed with sleep disturbance in epidemiologic surveys. © 2014 Associated Professional Sleep Societies, LLC.

  10. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T

    1999-01-01

    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

  11. Optimizing the radiation therapy dose prescription for pediatric medulloblastoma: minimizing the life years lost attributable to failure to control the disease and late complication risk.

    Science.gov (United States)

    Brodin, N Patrik; Vogelius, Ivan R; Björk-Eriksson, Thomas; Munck Af Rosenschöld, Per; Maraldo, Maja V; Aznar, Marianne C; Specht, Lena; Bentzen, Søren M

    2014-04-01

    A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling the primary disease. We compared the estimated LYL for three different treatments in 10 patients: 1) standard 3D conformal RT; 2) proton therapy; 3) risk-adaptive photon treatment lowering the dose to part of the craniospinal (CS) target volume situated close to critical risk organs. Late toxicity is important, with 0.75 LYL (95% CI 0.60-7.2 years) for standard uniform 24 Gy CS irradiation. However, recurrence risk dominates the total LYL with 14.2 years (95% CI 13.4-16.6 years). Compared to standard treatment, a risk-adapted strategy prescribing 12 Gy to the spinal volume encompassing the 1st-10th thoracic vertebrae (Th1-Th10), and 36 Gy to the remaining CS volume, estimated a LYL reduction of 0.90 years (95% CI -0.18-2.41 years). Proton therapy with 36 Gy to the whole CS volume was associated with significantly fewer LYL compared to the risk-adapted photon strategies, with a mean LYL difference of 0.50 years (95% CI 0.25-2.60 years). Optimization of RT prescription strategies considering both late complications and the risk of recurrence, an all-cause mortality dose painting approach, was demonstrated. The risk-adapted techniques compared favorably to the standard, and although in this context, the gain is small compared to estimated uncertainty, this study demonstrates a framework for all-cause mortality risk estimation, rather than evaluates direct clinical applicability of risk

  12. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  13. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    International Nuclear Information System (INIS)

    Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-01-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  14. Brain abscess with an unexpected finding: Actinomyces meyeri CNS infection

    DEFF Research Database (Denmark)

    Eiset, Andreas Halgreen; Thomsen, Marianne Kragh; Wejse, Christian

    -up. The source of infection was most likely periodontitis with spread to the lungs from aspiration or oropharyngeal secretion into the respiratory tract, alternatively from haematogenous spread. Conclusions: We report of the successful treatment of a cerebral abscess caused by A. meyeri with narrow spectrum......Background: CNS infection caused by Actinomyces spp. is rare and the subtype Actinomyces meyeri even rarer. Risk factors include periodontal disease and alcohol overuse. We present a case report of a 54-year-old female with dental and lung foci. Case history: A female was hospitalised with tonic...... oedema. By MRI an abscess was suspected and the patient was transferred to the department of neurosurgery, where drainage was performed. Microscopy revealed gram-positive cocci and gram-negative rods and iv. treatment with ceftriaxone 4g x 1 and metronidazole 1g x 1 was commenced. Pus cultures showed...

  15. Risk factors and direct medical cost of early versus late unplanned readmissions among diabetes patients at a tertiary hospital in Singapore.

    Science.gov (United States)

    Png, May Ee; Yoong, Joanne; Chen, Cynthia; Tan, Chuen Seng; Tai, E Shyong; Khoo, Eric Y H; Wee, Hwee Lin

    2018-02-20

    To examine the risk factors and direct medical costs associated with early (≤30 days) versus late (31-180 days) unplanned readmissions among patients with type 2 diabetes in Singapore. Risk factors and associated costs among diabetes patients were investigated using electronic medical records from a local tertiary care hospital from 2010 to 2012. Multivariable logistic regression was used to identify risk factors associated with early and late unplanned readmissions while a generalized linear model was used to estimate the direct medical cost. Sensitivity analysis was also performed. A total of 1729 diabetes patients had unplanned readmissions within 180 days of an index discharge. Length of index stay (a marker of acute illness burden) was one of the risk factors associated with early unplanned readmission while patient behavior-related factors, like diabetes-related medication adherence, were associated with late unplanned readmission. Adjusted mean cost of index admission was higher among patients with unplanned readmission. Sensitivity analysis yielded similar results. Existing routinely captured data can be used to develop prediction models that flag high risk patients during their index admission, potentially helping to support clinical decisions and prevent such readmissions.

  16. Novel agents in CNS myeloma treatment.

    Science.gov (United States)

    Gozzetti, Alessandro; Cerase, Alfonso

    2014-01-01

    Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

  17. Malignant lymphoma in central nervous system (CNS)

    International Nuclear Information System (INIS)

    Fujiyoshi, Kenji; Fukuyama, Hidenao; Akiguchi, Ichiro; Kameyama, Masakuni; Nishimura, Toshio.

    1984-01-01

    A 71-year-old male was admitted to Kohka Public Hospital on January 4, 1980, because of frequent vomiting and recent memory loss. Two weeks before admission upper G-I series showed no abnormalities. Physical and neurological examinations revealed no abnormalities except for slightly apathetic appearance and recent memory loss. Mild pleocytosis and marked increase of protein in CSF were observed. CT scan on January 17 showed high density areas in both medial sides of temporal lobes with remarkable contrast enhancement. His memory and, consciousness disturbances gradually aggravated, accompanied by abnormal density spreading around the ventricle walls like ventriculitis. He was transfered to Kyoto University Hospital on March 17, and malignant lymphoma was diagnosed on the basis of CSF cytology. Radiation and chemotherapy alleviated the CNS involvement and he regained normal mental function. On June 16, he developed pneumonia followed by status epilepticus. Autopsy findings revealed no lymphoid cell infiltration, but fibrous tissues in both hippocampal gyri and lymphomatous cells in the liver, which could not be suspected on clinical examinations. Apparent malignant lymphoma cells were not found in lymph nodes. This case indicated peculiar evolution of malignant lymphoma from liver to CNS or vice versa. We could not decide which organ was primary. CT findings of this case was very interesting; they resembled ventriculitis, which simulate tumors such as medulloblastoma or ependymoma spreading under ependymal lining. (author)

  18. An objective measure to identify pediatric liver transplant recipients at risk for late allograft rejection related to non-adherence.

    Science.gov (United States)

    Venkat, Veena L; Nick, Todd G; Wang, Yu; Bucuvalas, John C

    2008-02-01

    Non-adherence to a prescribed immunosuppressive regimen increases risk for late allograft rejection (LAR). We implemented a protocol for immunosuppression management which decreased variation in calcineurin inhibitor blood levels in pediatric liver transplant recipients by controlling for confounders such as physician practice variability. We hypothesized that patients with increased variation in tacrolimus blood levels despite implementation of the immunosuppression management protocol were at increased risk for LAR. We conducted a single center retrospective cohort study of 101 pediatric liver transplant recipients who were at least one year post liver transplantation and receiving tacrolimus for immunosuppression. The primary outcome variable was biopsy proven allograft rejection. Primary candidate predictor variables were the standard deviation (SD) of tacrolimus blood levels (a marker of drug level variability), mean tacrolimus blood level, age, and insurance type. SD of tacrolimus blood levels was determined for each patient from a minimum of four outpatient levels during the study period. Unadjusted and adjusted logistic regression models were used to determine the prognostic value of candidate predictors. The median and interquartile range of the SD of tacrolimus blood levels was 1.6 (1.1, 2.1). Eleven episodes of LAR occurred during the study period. Ten of the 11 episodes occurred in patients with tacrolimus blood level SD > 2. Insurance type, mean tacrolimus blood level and SD of tacrolimus blood levels were significantly related to LAR in the unadjusted analyses (ptype, mean and SD of tacrolimus blood levels was significantly associated with LAR (validated C-statistic = 0.88, p = 0.012). The adjusted odds of rejection for a one unit increase in the SD of tacrolimus blood level was 3.49 (95% CI 1.31 to 9.29). Effects of age and insurance status on LAR did not provide independent prognostic value after controlling for SD. Variation in tacrolimus blood

  19. Trends in baseline CD4 cell counts and risk factors for late antiretroviral therapy initiation among HIV-positive patients in Shanghai, a retrospective cross-sectional study.

    Science.gov (United States)

    Sun, Jianjun; Liu, Li; Shen, Jiayin; Chen, Panpan; Lu, Hongzhou

    2017-04-19

    There are few studies focus on the factors underlying the late initiation of ART in China. We analyzed the trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART in Shanghai, China. A retrospective cross-sectional survey was made in the Department of Infectious Disease of Shanghai Public Health Clinical Center which is a designated diagnosis and treatment center for HIV-positive patients in Shanghai during the period of January 1st, 2008--June 30th, 2014. Late ART initiation was defined as a CD4 cell count 30 years) (p HIV exposure who are male, older even heterosexual orientation should be given more opportunities to receive frequently screening, earlier diagnoses and timely treatment.

  20. Risk factors for late-onset generalized anxiety disorder: results from a 12-year prospective cohort (the ESPRIT study).

    Science.gov (United States)

    Zhang, X; Norton, J; Carrière, I; Ritchie, K; Chaudieu, I; Ancelin, M-L

    2015-03-31

    Generalized anxiety disorder (GAD) is a chronic and highly prevalent disorder associated with increased disability and mortality in the elderly. Treatment is difficult with low rate of full remission, thus highlighting the need to identify early predictors for prevention in elderly people. The aim of this study is to identify and characterize incident GAD predictors in elderly people. A total of 1711 individuals aged 65 years and above and free of GAD at baseline were randomly recruited from electoral rolls between 1999 and 2001 (the prospective ESPRIT study). The participants were examined at baseline and five times over 12 years. GAD and psychiatric comorbidity were diagnosed with a standardized psychiatric examination, the Mini-International Neuropsychiatry Interview on the basis of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria and validated by a clinical panel. During the follow-up, 8.4% (95% confidence interval=7.1-9.7%) of the participants experienced incident GAD, 80% being first episodes; the incident rate being 10 per 1000 person-years. The principal predictors of late-onset incident GAD over 12 years derived from a multivariate Cox model were being female, recent adverse life events, having chronic physical (respiratory disorders, arrhythmia and heart failure, dyslipidemia, cognitive impairment) and mental (depression, phobia and past GAD) health disorders. Poverty, parental loss or separation and low affective support during childhood, as well as history of mental problems in parents were also significantly and independently associated with incident GAD. GAD appears as a multifactorial stress-related affective disorder resulting from both proximal and distal risk factors, some of them being potentially modifiable by health care intervention.

  1. Major Late Toxicities After Conformal Radiotherapy for Nasopharyngeal Carcinoma-Patient- and Treatment-Related Risk Factors

    International Nuclear Information System (INIS)

    Lee, Anne W.M.; Ng, W.T.; Hung, W.M.; Choi, C.W.; Tung, Raymond; Ling, Y.H.; Cheng, Peter T.C.; Yau, T.K.; Chang, Amy T.Y.; Leung, Samuel K.C.; Lee, Michael C.H.; Bentzen, Soren M.

    2009-01-01

    Purpose: To retrospectively analyze the factors affecting late toxicity for nasopharyngeal carcinoma. Methods and Materials: Between 1998 and 2003, 422 patients were treated with a conformal technique with 2-Gy daily fractions to a total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in 232 patients and accelerated fractionation (6 fractions weekly) in 190 patients. One hundred seventy-one patients were treated with the basic radiotherapy course alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy (Group 3). Results: The 5-year overall toxicity rate was significantly greater in Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate analyses showed that age and concurrent chemotherapy were significant factors. The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95% confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the cochlea was another significant factor affecting deafness, with a hazard ratio of 1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18% vs. 7%; and Group 3, 22% vs. 14%). Conclusion: The therapeutic margin for nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain necrosis could result from dose escalation. The significant factors affecting the risk of deafness included age, concurrent chemoradiotherapy, and greater radiation dose to the cochlea

  2. Early versus late percutaneous revascularization in patients hospitalized with non ST-segment elevation myocardial infarction: The atherosclerosis risk in communities surveillance study.

    Science.gov (United States)

    Arora, Sameer; Matsushita, Kunihiro; Qamar, Arman; Stacey, R Brandon; Caughey, Melissa C

    2018-02-01

    Current guidelines recommend early invasive intervention (<24 hr) for high risk patients with non-ST-segment elevation myocardial infarction (NSTEMI). A delayed invasive strategy (24-72 hr) is considered reasonable for low risk patients. The real-world effectiveness of this strategy is unknown. The ARIC Study has conducted hospital surveillance of acute myocardial infarction (MI) since 1987. NSTEMI was classified using a validated algorithm. We limited our study to patients undergoing early (<24 hr of the event onset), or late (≥24 hr) percutaneous coronary intervention (PCI). Patients were stratified into low (TIMI score 2-4), and high risk (TIMI score 5-7, or presence of cardiogenic shock, ventricular fibrillation, or cardiac arrest). Associations between early versus late PCI and mortality were analyzed using multivariable logistic regression adjusted for demographics, hospitalization year, TIMI score, and comorbidities. From 1987 to 2012, 6,746 patients were hospitalized with NSTEMI and underwent PCI. Most were white (79%), male (68%), with mean age 61 years. The 28-day and 1-year mortality were 2% and 5%, respectively. Most revascularizations (65%) were late. After accounting for potential confounders, early PCI was associated with a 58% reduced 28-day mortality (OR = 0.42; 95% CI: 0.21-0.84) for the entire population, and 57% reduced mortality (OR = 0.43; 95% CI: 0.21-0.88) for high risk patients. By 1-year of follow up, there was no significant difference in mortality with respect to early vs. late PCI. In hospitalized NSTEMI patients with high risk of clinical events, early PCI is associated with improved 28-day survival. © 2017 Wiley Periodicals, Inc.

  3. Transplanting oligodendrocyte progenitors into the adult CNS

    International Nuclear Information System (INIS)

    Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.

    1997-01-01

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

  4. Biomarkers for CNS involvement in pediatric lupus

    Science.gov (United States)

    Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

    2015-01-01

    CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

  5. Palmitoylethanolamide in CNS health and disease.

    Science.gov (United States)

    Mattace Raso, Giuseppina; Russo, Roberto; Calignano, Antonio; Meli, Rosaria

    2014-08-01

    The existence of acylethanolamides (AEs) in the mammalian brain has been known for decades. Among AEs, palmitoylethanolamide (PEA) is abundant in the central nervous system (CNS) and conspicuously produced by neurons and glial cells. Antihyperalgesic and neuroprotective properties of PEA have been mainly related to the reduction of neuronal firing and to control of inflammation. Growing evidence suggest that PEA may be neuroprotective during CNS neurodegenerative diseases. Advances in the understanding of the physiology and pharmacology of PEA have potentiated its interest as useful biological tool for disease management. Several rapid non-genomic and delayed genomic mechanisms of action have been identified for PEA as peroxisome proliferator-activated receptor (PPAR)-α dependent. First, an early molecular control, through Ca(+2)-activated intermediate- and/or big-conductance K(+) channels opening, drives to rapid neuronal hyperpolarization. This is reinforced by the increase of the inward Cl(-) currents due to the modulation of the gamma aminobutyric acid A receptor and by the desensitization of the transient receptor potential channel type V1. Moreover, the gene transcription-mediated mechanism sustains the long-term anti-inflammatory effects, by reducing pro-inflammatory enzyme expression and increasing neurosteroid synthesis. Overall, the integration of these different modes of action allows PEA to exert an immediate and prolonged efficacious control in neuron signaling either on inflammatory process or neuronal excitability, maintaining cellular homeostasis. In this review, we will discuss the effect of PEA on metabolism, behavior, inflammation and pain perception, related to the control of central functions and the emerging evidence demonstrating its therapeutic efficacy in several neurodegenerative diseases. Copyright © 2014. Published by Elsevier Ltd.

  6. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Armoogum, Kris S., E-mail: kris.armoogum@nhs.net [Department of Radiotherapy Physics, Royal Derby Hospital, Derby Hospitals NHS Foundation Trust, Uttoxeter Road, Derby DE22 3NE (United Kingdom); Thorp, Nicola [The Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Bebington, Wirral CH63 4JY (United Kingdom)

    2015-04-28

    Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  7. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Directory of Open Access Journals (Sweden)

    Kris S. Armoogum

    2015-04-01

    Full Text Available Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  8. A case-control study to examine the association between breastfeeding during late pregnancy and risk of a small-for-gestational-age birth in Lima, Peru.

    Science.gov (United States)

    Pareja, Rossina G; Marquis, Grace S; Penny, Mary E; Dixon, Philip M

    2015-04-01

    Excessive demands on maternal nutritional status may be a risk factor for poor birth outcomes. This study examined the association between breastfeeding during late pregnancy (≥ 28 weeks) and the risk of having a small-for-gestational-age (SGA) newborn, using a matched case-control design (78 SGA cases: birthweight project midwives visited daily three government hospitals in Lima, Peru and identified cases and matched controls based on hospital, gestational age, and inter-gestational period. Mothers were interviewed and clinical chart extractions were completed. Factors associated with risk of SGA were assessed by their adjusted odds ratios (aOR) from conditional logistic regression. Exposure to an overlap of breastfeeding during late pregnancy was not associated with an increased risk of having a SGA newborn [aOR=0.58, 95% confidence interval (CI): 0.10-3.30]. However, increased risk was associated with having a previous low-birthweight birth (aOR=6.53; 95% CI: 1.43-29.70) and a low intake of animal source foods (power are needed to definitively examine this possible association and clarify whether there are other risks to the new baby, the toddler and the pregnant woman. © 2012 Blackwell Publishing Ltd.

  9. Late acute humoral rejection in low-risk renal transplant recipients induced with an interleukin-2 receptor antagonist and maintained with standard therapy: preliminary communication.

    Science.gov (United States)

    Morales, J; Contreras, L; Zehnder, C; Pinto, V; Elberg, M; Araneda, S; Herzog, C; Calabran, L; Aguiló, J; Ferrario, M; Buckel, E; Fierro, J A

    2011-01-01

    Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. CT studies before and after CNS treatment for acute lymphoblastic leukemia and malignant non-Hodgkin's lymphoma in childhood

    International Nuclear Information System (INIS)

    Kretzschmar, K.; Gutjahr, P.; Kutzner, J.

    1980-01-01

    CT was performed on 72 children with acute lymphoblasitc leukemia or non-Hodgkin's lymphoma. Thirty-two of these patients were investigated prior to CNS radiation and intrathecal methotrexate therapy. Ten of these patients (31%) were known to have hydrocephalic dilatation of the CSF spaces. Clinical data and subsequent observations with analysis of the CT findings show that no difference in the attenuation values of brain tissue occurs in the absence of a CNS relapse. The percentage of abnormal findings before and after therapy remains constant. The adverse late effects described in the CT literature seem principally to be damage diagnosed too late. It is questionable if the CT demonstration of dilated CSF spaces before treatment has a prognostic significance. (orig.)

  11. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

    DEFF Research Database (Denmark)

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H

    2016-01-01

    with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration...

  12. Chronic high Epstein-Barr viral load state and risk for late-onset posttransplant lymphoproliferative disease/lymphoma in children.

    Science.gov (United States)

    Bingler, M A; Feingold, B; Miller, S A; Quivers, E; Michaels, M G; Green, M; Wadowsky, R M; Rowe, D T; Webber, S A

    2008-02-01

    Increased use of serial EBV-PCR monitoring after pediatric transplantation has led to the identification of asymptomatic patients who carry very high viral loads over prolonged periods. The significance of this high-load state is unknown. We speculated that this state may identify patients at high risk for development of late PTLD/lymphoma. We reviewed data on 71 pediatric heart recipients who had serial viral load monitoring since 1997. Chronic high-load state was defined as the presence of >16,000 genome copies/mL whole blood on > or =50% of samples over at least 6 months. Among 20 high-load carriers (eight following prior PTLD, seven with prior symptomatic EBV infection, five without previous EBV disease), 9 (45%) developed late-onset PTLD 2.5-8.4 years posttransplant (including with four Burkitt's lymphoma). Among 51 controls with low (n = 39) or absent (n = 12) loads, only 2 (4%; p < 0.001 absent/low vs. high load) developed late PTLD/lymphoma. By multivariable analysis, high-load carrier state (OR = 12.4, 95% CI 2.1-74.4) and prior history of PTLD (OR = 10.7, 95% CI 1.9-60.6) independently predicted late PTLD. A chronic high EBV-load state is not benign and is a predictor of de novo or recurrent PTLD.

  13. Regional spore dispersal as a factor in disease risk warnings for potato late blight: a proof of concept

    NARCIS (Netherlands)

    Kessel, G.J.T.; Skelsey, P.; Holtslag, A.A.M.; Moene, A.F.; Werf, van der W.

    2009-01-01

    This study develops and tests novel approaches that significantly reduce the fungicide input necessary for potato late blight control while maintaining the required high level of disease control. The central premise is that fungicide inputs can be reduced by reducing dose rates on more resistant

  14. Early and late onset depression in young and middle aged adults : Differential symptomatology, characteristics and risk factors?

    NARCIS (Netherlands)

    Korten, Nicole C. M.; Comijs, Hannie C.; Lamers, Femke; Penninx, Brenda W. J. H.

    Background: Early onset depression (EOD) and late onset depression (LOD) may be different phenomena. In this study, differences between EOD and LOD in symptomatology, psychiatric characteristics and psychosocial/somatic factors were examined. Methods: Baseline data were from 1104 participants with a

  15. A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

    International Nuclear Information System (INIS)

    Ahmed, Awad A.; Egleston, Brian; Alcantara, Pino; Li, Linna; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2013-01-01

    Background: There are no well-established normal tissue sparing dose–volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. Methods and Materials: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). Results: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P 68 years. Conclusion: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored

  16. Fifth CNS international steam generator conference

    International Nuclear Information System (INIS)

    2006-01-01

    The Fifth CNS International Steam Generator Conference was held on November 26-29, 2006 in Toronto, Ontario, Canada. In contrast with other conferences which focus on specific aspects, this conference provided a wide ranging forum on nuclear steam generator technology from life-cycle management to inspection and maintenance, functional and structural performance characteristics to design architecture. The 5th conference has adopted the theme: 'Management of Real-Life Equipment Conditions and Solutions for the Future'. This theme is appropriate at a time of transition in the industry when plants are looking to optimize the performance of existing assets, prevent costly degradation and unavailability, while looking ahead for new steam generator investments in life-extension, replacements and new-build. More than 50 technical papers were presented in sessions that gave an insight to the scope: life management strategies; fouling, cleaning and chemistry; replacement strategies and new build design; materials degradation; condition assessment/fitness for service; inspection advancements and experience; and thermal hydraulic performance

  17. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

    Science.gov (United States)

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

    2015-08-18

    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  18. Analysis of perfusion weighted image of CNS lymphoma

    International Nuclear Information System (INIS)

    Lee, In Ho; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik

    2010-01-01

    Purpose: It is difficult to differentiate CNS lymphoma from other tumors such as malignant gliomas, metastases, or meningiomas with conventional MR imaging, because the imaging findings are overlapped between these tumors. The purpose of this study is to investigate the perfusion weighted MR imaging findings of CNS lymphomas and to compare the relative cerebral blood volume ratios between CNS lymphomas and other tumors such as high grade gliomas, metastases, or meningiomas. Materials and methods: We retrospectively reviewed MRI findings and clinical records in 13 patients with pathologically proven CNS lymphoma between January 2006 and November 2008. We evaluated the relative cerebral blood volume ratios of tumor, which were obtained by dividing the values obtained from the normal white matter on MRI. Results: Total 13 patients (M:F = 8:5; age range 46-67 years, mean age 52.3 years) were included. The CNS lymphomas showed relatively low values of maximum relative CBV ratio in most patients regardless of primary or secondary CNS lymphoma. Conclusion: Perfusion weighted image may be helpful in the diagnosis of CNS lymphoma in spite of primary or secondary or B cell or T cell.

  19. Maternal History and Uterine Artery Doppler in the Assessment of Risk for Development of Early- and Late-Onset Preeclampsia and Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Elisa Llurba

    2009-01-01

    Full Text Available Objective. To examine the value of one-step uterine artery Doppler at 20 weeks of gestation in the prediction pre-eclampsia (PE and/or intrauterine growth restriction (IUGR. Methods. A prospective multicentre study that included all women with singleton pregnancies at 19–22 weeks of gestation (w. The mean pulsatility index (mPI of both uterine arteries was calculated. Receiver-operating characteristics curves (ROC were drawn to compare uterine artery Doppler and maternal risk factors for the prediction of early-onset PE and/or IUGR (before 32 w and late-onset PE and/or IUGR. Results. 6,586 women were included in the study. Complete outcome data was recorded for 6,035 of these women (91.6%. PE developed in 75 (1.2% and IUGR in 69 (1.1% cases. Uterine Doppler mPI was 0.99 and the 90th centile was 1.40. For 10% false-positive rate, uterine Doppler mPI identified 70.6% of pregnancies that subsequently developed early-onset PE and 73.3% of pregnancies that developed early-onset IUGR. The test had a lower detection rate for the late-onset forms of the disease (23.5% for PE and 30% for IUGR. Maternal history has a low sensitivity in the detection of early-onset cases, although it is better at detecting late-onset PE. Conclusion. Uterine artery Doppler and maternal risk factors seem to select two different populations - early and late-onset PE which might suggest a different pathogenesis.

  20. 3rd ENRI International Workshop on ATM/CNS

    CERN Document Server

    2014-01-01

    The Electronic Navigation Research Institute (ENRI) held its third International Workshop on ATM / CNS in 2013 with the theme of "Drafting the future sky". There is worldwide activity taking place in the research and development of modern air traffic management (ATM) and its enabling technologies in Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization of air traffic management and control. At this workshop, leading experts in  research, industry and academia from around the world met to share their ideas and approaches on ATM/CNS related topics.

  1. Autoimmune process in CNS under Cs-137 inner irradiation

    International Nuclear Information System (INIS)

    Lisyany, N.I.; Liubich, L.D.

    1996-01-01

    Autoimmune hypothesis as to the development of radiation-induced brain injuries stands high among the concepts of the CNS post-radiation damage pathogenesis. To study the changes occurring in a living organism affected by a small-dose radiation due to incorporated radionuclides as well as to create adequate models are of critical importance in the post-Chernobyl period. The effects of chronic small-dose inner radiation on the development of autoimmune responses were evaluated by determining the level of the CNS proteins and protein-induced antibodies to the CNS components. (author)

  2. In vivo human apolipoprotein E isoform fractional turnover rates in the CNS.

    Directory of Open Access Journals (Sweden)

    Kristin R Wildsmith

    Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.

  3. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Directory of Open Access Journals (Sweden)

    Rodríguez de Lores Arnaiz Georgina

    2006-04-01

    Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process

  4. Attenuated hypocholesterolemia following severe trauma signals risk for late ventilator-associated pneumonia, ventilator dependency, and death: a retrospective study of consecutive patients

    Directory of Open Access Journals (Sweden)

    Chirichella Thomas J

    2011-03-01

    Full Text Available Abstract Background Post-traumatic ventilator-associated pneumonia (VAP is a substantial clinical problem that increases hospital costs and typically adds to the duration of mechanical ventilation. We evaluated the impact of VAP on ventilator days. We also assessed 48-hour total blood cholesterol (TC and other potential risk factors for the development of VAP. Methods We performed a retrospective study of consecutive trauma patients requiring emergency tracheal intubation and evaluated TC, age, gender, ethanol status, smoker status, injury mechanism, chest injury, brain injury, Injury Severity Score (ISS, shock, day-one hypoxemia, and RBC transfusion as potential risks for VAP. Results The 152 patients had ISS 28.1, brain injury 68.4%, VAP 50.0%, ventilator days 14.3, and death 9.9%. Ventilator days were increased with late VAP (p Conclusions Severe traumatic injury produced substantial hypocholesterolemia that is greater with chest injury, shock, and RBC transfusion, but less with brain injury. Total blood cholesterol tended to decrease with increasing injury severity. However, attenuated hypocholesterolemia (ISS ≥ 20-&-TC ≥ 90 mg/dL represents a unique response that can occur with critical injury. Attenuated hypocholesterolemia signals early risk for late VAP, ventilator dependency, and death.

  5. Myocardial area at risk after ST-elevation myocardial infarction measured with the late gadolinium enhancement after scar remodeling and T2-weighted cardiac magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Engstrøm, Thomas; Mathiasen, Anders B

    2011-01-01

    To evaluate the myocardial area at risk (AAR) measured by the endocardial surface area (ESA) method on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) when applied after scar remodeling (3 months after index infarction) compared to T2-weighted CMR imaging. One hundred...... and sixty nine patients with ST-elevation myocardial infarction, treated with primary percutaneous coronary intervention, underwent one CMR within 1 week after index treatment to determine the AAR with T2-weighted imaging and a second scan 3 months after to measure AAR with the ESA method...

  6. Myocardial area at risk after ST-elevation myocardial infarction measured with the late gadolinium enhancement after scar remodeling and T2-weighted cardiac magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Engstrøm, Thomas; Mathiasen, Anders B

    2012-01-01

    To evaluate the myocardial area at risk (AAR) measured by the endocardial surface area (ESA) method on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) when applied after scar remodeling (3 months after index infarction) compared to T2-weighted CMR imaging. One hundred...... and sixty nine patients with ST-elevation myocardial infarction, treated with primary percutaneous coronary intervention, underwent one CMR within 1 week after index treatment to determine the AAR with T2-weighted imaging and a second scan 3 months after to measure AAR with the ESA method...

  7. Air pollution: mechanisms of neuroinflammation and CNS disease.

    Science.gov (United States)

    Block, Michelle L; Calderón-Garcidueñas, Lilian

    2009-09-01

    Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.

  8. A map of taste neuron projections in the Drosophila CNS

    Indian Academy of Sciences (India)

    2014-07-08

    Jul 8, 2014 ... information that they represent. The extensive ... physiology and behaviour in the wild type and in these mutants .... taste information is processed in the CNS. 2. ..... gene affecting the specificity of the chemosensory neurons of.

  9. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu

    2016-01-01

    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  10. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Directory of Open Access Journals (Sweden)

    Diamantina Vasilatou

    2014-01-01

    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  11. CNS-directed gene therapy for lysosomal storage diseases

    OpenAIRE

    Sands, Mark S; Haskins, Mark E

    2008-01-01

    Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders usually caused by deficient activity of a single lysosomal enzyme. As most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems, including the central nervous system (CNS). At least 75% of all LSDs have a significant CNS component. Approaches such as bone marrow transplantation (BMT) or enzyme replacement therapy (ERT) can effectively treat the systemic dis...

  12. [Comparision of risk factors and pathogens in patients with early- and late-onset ventilator-associated pneumonia in intensive care unit].

    Science.gov (United States)

    Liang, Y J; Li, Z L; Wang, L; Liu, B Y; Ding, R Y; Ma, X C

    2017-10-01

    Objective: To compare risk factors and bacterial etiology in patients with early-onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care unit (ICU). Methods: This prospective cohort study enrolled mechanically ventilated patients hospitalized for more than 48 hours in the first affiliated hospital, China Medical University from Jan 2012 to Jun 2016. Subjects were classified by ventilator status: early-onset VAP (VAP) or late-onset VAP (≥ 5 d ventilation, L-VAP). Potential risk factors and pathogen were evaluated. Results: A total of 4 179 patients in adult ICU were screened, 3 989 (95.5%) of whom were mechanically ventilated, 962 patients with mechanical ventilation time ≥ 48 h. VAP developed in 142 patients. E-VAP and L-VAP had different potential risk factors based on statistical analysis.Independent risk factors for E-VAP included male ( OR =1.825, 95% CI 1.006-3.310), chronic obstructive pulmonary disease (COPD; OR =3.746, 95% CI 1.795-7.818), emergency intubation ( OR =1.932, 95% CI 1.139-3.276), aspiration ( OR =3.324, 95% CI 1.359-8.130). Whereas independent risk factors for L-VAP were coma ( OR =2.335, 95% CI 1.300-4.194), renal dysfunction ( OR =0.524, 95% CI 0.290-0.947), emergency intubation ( OR =2.184, 95% CI 1.334-3.574). Mortality in E-VAP and L-VAP group were both higher than the non-VAP group[30.2%(19/63)vs 19.8%(162/820), P =0.044; 29.1%(23/79) vs 19.8%(162/820), P =0.046]. The pathogens isolated from early-onset versus late-onset VAP were not significantly different between groups, which the most common ones were acinetobacter baumannii, pseudomonas aeruginosa and klebsiella pneumoniae. Conclusion: E-VAP and L-VAP have different risk factors, however related pathogens are similar. Different specific preventive strategies are suggested based on different onset of VAP.

  13. Risky Decision Making in a Laboratory Driving Task Is Associated with Health Risk Behaviors during Late Adolescence but Not Adulthood

    Science.gov (United States)

    Kim-Spoon, Jungmeen; Kahn, Rachel; Deater-Deckard, Kirby; Chiu, Pearl; Steinberg, Laurence; King-Casas, Brooks

    2016-01-01

    Adolescence is characterized by increasing incidence of health risk behaviors, including experimentation with drugs and alcohol. To fill the gap in our understanding of the associations between risky decision-making and health risk behaviors, we investigated associations between laboratory-based risky decision-making using the Stoplight task and…

  14. The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Maraldo, M V; Jørgensen, M; Brodin, N P

    2014-01-01

    BACKGROUND: The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT(IFRT), Modified IFRT (m......IFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique. PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage I......–II classical HL patients lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow...

  15. Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

    International Nuclear Information System (INIS)

    Goldsmith, Christy; Haviland, Joanne; Tsang, Yat; Sydenham, Mark; Yarnold, John

    2011-01-01

    Background and Purpose: Large breast size is associated with an increased risk of late adverse effects after breast conservation surgery and radiotherapy, even when 3D dosimetry is used. The purpose of this study is to test the hypothesis that residual dose inhomogeneity is sufficient to explain the association. Methods: Patients previously treated after breast conservation surgery with whole breast radiotherapy using 3D dosimetry and followed up in the UK FAST hypofractionation trial were selected for this analysis. The residual level of dose inhomogeneity across the whole breast treatment volume was used to test for association between residual dosimetry and post-treatment change in breast appearance at 2 years post-radiotherapy. Results: At 2 years, 201/279 (72%) of women had no change in photographic breast appearance, 61 (22%) had mild change and 17 (6%) had marked change. Breast size and dosimetry were both significantly associated with late effects in univariate analyses, but only breast size remained an independent significant risk factor for change in breast appearance when included in a multiple regression model together with other prognostic factors (p = 0.006 for trend). Conclusion: Large-breasted women are more likely to suffer change in breast size and shape after whole breast radiotherapy delivered using 3D dosimetry, but residual dose inhomogeneity is insufficient to explain the association.

  16. 10-Year cardiovascular event risks for women who experienced hypertensive disorders in late pregnancy: the HyRAS study

    Directory of Open Access Journals (Sweden)

    Ponjee Gabrielle

    2010-06-01

    Full Text Available Abstract Background Cardiovascular disease is the cause of death in 32% of women in the Netherlands. Prediction of an individual's risk for cardiovascular disease is difficult, in particular in younger women due to low sensitive and specific tests for these women. 10% to 15% of all pregnancies are complicated by hypertensive disorders, the vast majority of which develop only after 36 weeks of gestation. Preeclampsia and cardiovascular disease in later life show both features of "the metabolic syndrome" and atherosclerosis. Hypertensive disorders in pregnancy and cardiovascular disease may develop by common pathophysiologic pathways initiated by similar vascular risk factors. Vascular damage occurring during preeclampsia or gestational hypertension may contribute to the development of future cardiovascular disease, or is already present before pregnancy. At present clinicians do not systematically aim at the possible cardiovascular consequences in later life after a hypertensive pregnancy disorder at term. However, screening for risk factors after preeclampsia or gestational hypertension at term may give insight into an individual's cardiovascular risk profile. Methods/Design Women with a history of preeclampsia or gestational hypertension will be invited to participate in a cohort study 2 1/2 years after delivery. Participants will be screened for established modifiable cardiovascular risk indicators. The primary outcome is the 10-year cardiovascular event risk. Secondary outcomes include differences in cardiovascular parameters, SNP's in glucose metabolism, and neonatal outcome. Discussion This study will provide evidence on the potential health gains of a modifiable cardiovascular risk factor screening program for women whose pregnancy was complicated by hypertension or preeclampsia. The calculation of individual 10-year cardiovascular event risks will allow identification of those women who will benefit from primary prevention by tailored

  17. Bovine-associated CNS species resist phagocytosis differently

    Science.gov (United States)

    2013-01-01

    Background Coagulase-negative staphylococci (CNS) cause usually subclinical or mild clinical bovine mastitis, which often remains persistent. Symptoms are usually mild, mostly only comprising slight changes in the appearance of milk and possibly slight swelling. However, clinical mastitis with severe signs has also been reported. The reasons for the differences in clinical expression are largely unknown. Macrophages play an important role in the innate immunity of the udder. This study examined phagocytosis and killing by mouse macrophage cells of three CNS species: Staphylococcus chromogenes (15 isolates), Staphylococcus agnetis (6 isolates) and Staphylococcus simulans (15 isolates). Staphylococcus aureus (7 isolates) was also included as a control. Results All the studied CNS species were phagocytosed by macrophages, but S. simulans resisted phagocytosis more effectively than the other CNS species. Only S. chromogenes was substantially killed by macrophages. Significant variations between isolates were seen in both phagocytosis and killing by macrophages and were more common in the killing assays. Significant differences between single CNS species and S. aureus were observed in both assays. Conclusion This study demonstrated that differences in the phagocytosis and killing of mastitis-causing staphylococci by macrophages exist at both the species and isolate level. PMID:24207012

  18. Is The Late Mandibular Fracture From Third Molar Extraction a Risk Towards Malpractice? Case Report with the Analysis of Ethical and Legal Aspects

    Directory of Open Access Journals (Sweden)

    Weuler dos Santos Silva

    2017-06-01

    Full Text Available Objectives: The present study reports a case of late mandibular fracture due to third molar extraction and highlights the inherent clinical, ethical and legal aspects related to this surgical complication. Material and Methods: A female patient underwent surgical procedure for the extraction of the mandibular right third molar. Two days after the surgery the patient reported pain and altered occlusion in the right side of the mandible. After clinical and radiographic re-examination, the diagnosis of late mandibular fracture was established. A second surgery, under general anaesthesia, was performed for the fixation of the mandibular bone. Results: The fractured parts were reduced and fixed with locking plate systems and 2 mm screws following load-sharing principles. The masticatory function showed optimal performance within 7 and 21 days after the surgery. Complete bone healing was observed within 1 year of follow-up. Conclusions: For satisfactory surgical outcomes, adequate surgical planning and techniques must be performed. Signed informed consents explaining the risks and benefits of the treatment must be used to avoid ethical and legal disputes in dentistry.

  19. Late Budgets

    DEFF Research Database (Denmark)

    Andersen, Asger Lau; Lassen, David Dreyer; Nielsen, Lasse Holbøll Westh

    are negative rather than positive; and when there is divided government. We test the hypotheses of the model using a unique data set of late budgets for US state governments, based on dates of budget approval collected from news reports and a survey of state budget o¢ cers for the period 1988...

  20. Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant

    DEFF Research Database (Denmark)

    Gabriel, Melissa; Shaw, Bronwen E; Brazauskas, Ruta

    2017-01-01

    Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients...

  1. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Directory of Open Access Journals (Sweden)

    Alerie Guzman De La Fuente

    2017-08-01

    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  2. Can injured adult CNS axons regenerate by recapitulating development?

    Science.gov (United States)

    Hilton, Brett J; Bradke, Frank

    2017-10-01

    In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.

  3. Information needs of survivors and families after childhood CNS tumor treatment: a population-based study.

    Science.gov (United States)

    Hovén, Emma; Lannering, Birgitta; Gustafsson, Göran; Boman, Krister K

    2018-05-01

    This study examines information needs and satisfaction with provided information among childhood central nervous system (CNS) tumor survivors and their parents. In a population-based sample of 697 adult survivors in Sweden, 518 survivors and 551 parents provided data. Information needs and satisfaction with information were studied using a multi-dimensional standardized questionnaire addressing information-related issues. Overall, 52% of the survivors and 48% of the parents reported no, or only minor, satisfaction with the extent of provided information, and 51% of the survivors expressed a need for more information than provided. The information received was found useful (to some extent/very much) by 53%, while 47% did not find it useful, or to a minor degree only. Obtaining written material was associated with greater satisfaction and usefulness of information. Dissatisfaction with information was associated with longer time since diagnosis, poorer current health status and female sex. The survivors experienced unmet information needs vis-à-vis late effects, illness education, rehabilitation and psychological services. Overall, parents were more dissatisfied than the survivors. These findings have implications for improvements in information delivery. Information in childhood CNS tumor care and follow-up should specifically address issues where insufficiency was identified, and recognize persistent and with time changing needs at the successive stages of long-term survivorship.

  4. Study on the risk of late damage in humans after incorporation of the short-lived alpha emitter Ra-224

    International Nuclear Information System (INIS)

    Wick, R.R.; Nekolla, E.A.; Kellerer, A.M.; Goessner, W.

    2003-01-01

    An epidemiological study has been carried out at the GSF - National Research Center for Environment and Health - between 1948 and 1975, on 1460 ankylosing spondylitis (AS) patients. The aim of the study was to ascertain the late health effects suffered by these patients who had received repeated intravenous injections of the short lived α-emitter 224 Ra. These patients have been followed together with a control group of 1323 ankylosing spondylitis patients not treated with radioactive drugs and/or X-rays. Causes of death have been ascertained for 842 exposed patients and 861 controls by the end of 2002. In the exposed group there has been a total of 219 malignant diseases and 206 cases among the controls. In particular, we observed 15 cases of leukaemia in the exposure group and 8 cases of leukaemia in the control group. Further subclassification of the leukaemias demonstrated a high increase of myeloid leukaemia in the exposure group (9 cases obs. vs. 2.5 cases exp.), and out of these especially the acute myeloid leukaemias (6 cases observed vs. 1.6 expected), whereas in the control group the observed cases are within the expected range (3 myeloid leukaemias vs. 2.6 cases). Out of these 6 cases of myeloid leukaemia, 3 cases have been observed at doses comparable to those of the currently applied 224 Ra treatment with the preparation SpondylAT registered , in one case the 224 Ra-dose was the 0.6fold, in another case 1.6fold, whereas in one case the total dose could not be verified exactly. The enhanced leukaemia incidence in our exposed group is in line with results from animal experiments in mice having been injected with bone seeking α-emitters given at low dose rates. (orig.) [de

  5. Clinical and imaging features associated with an increased risk of early and late stroke in patients with symptomatic carotid disease

    DEFF Research Database (Denmark)

    Naylor, A R; Sillesen, H; Schroeder, T V

    2015-01-01

    of acute cerebral injury on CT/MRI; (iii) Gray Scale Median (GSM) predictive algorithms (based......-99% stenoses will suffer a stroke within 72 hours of their index symptom. Currently, there are insufficient validated data to identify highest-risk patients for emergency carotid endarterectomy (CEA), but an increased risk of stroke appears to be predicted by (i) an ABCD(2) score of 4-7; (ii) the presence...... on accessible imaging strategies) for identifying acutely symptomatic patients with highly unstable plaques for emergency CEA. MEDIUM TO LONG TERM: In the randomised trials, about 70% of patients with symptomatic 70-99% stenoses were stroke-free on "best medical therapy" at 5 years. Clinical predictors...

  6. Relationship between serum anti-Mullerian hormone with vitamin D and metabolic syndrome risk factors in late reproductive-age women.

    Science.gov (United States)

    Kim, Sunmie; Kim, Jin Ju; Kim, Min-Jeong; Han, Kyung Hee; Lee, Jung Ryeol; Suh, Chang Suk; Choi, Young Min; Kim, Seok Hyun

    2018-04-01

    The relationship between serum anti-Mullerian hormone (AMH) with vitamin D (25OH-D) and metabolic syndrome (MetS) risk was evaluated in healthy, late reproductive-age (35-49 years) women with regular menstrual cycles. Among the 291 participants (mean age = 42.5 years), most (76.6%, n = 223) were serum vitamin D insufficient (D were 2.04 ng/mL and 15.9 ng/mL, respectively. There was no correlation between AMH and 25OH-D after adjustment for age (r = -0.093, p = 0.113). Subjects with higher MetS score, higher waist circumference, and higher diastolic blood pressure had significantly higher serum AMH levels when adjusted for age, but the association attenuated when BMI was included. There was no significant correlation between MetS risk components with serum level of AMH or vitamin D. In conclusion, there was no association between AMH with serum 25OH-D or MetS risk factors in this population.

  7. Molecular basis for increased risk for late-onset Alzheimer disease due to the naturally occurring L28P mutation in apolipoprotein E4.

    Science.gov (United States)

    Argyri, Letta; Dafnis, Ioannis; Theodossiou, Theodossis A; Gantz, Donald; Stratikos, Efstratios; Chroni, Angeliki

    2014-05-02

    The apolipoprotein (apo) E4 isoform has consistently emerged as a susceptibility factor for late-onset Alzheimer disease (AD), although the exact mechanism is not clear. A rare apoE4 mutant, apoE4[L28P] Pittsburgh, burdens carriers with an added risk for late-onset AD and may be a useful tool for gaining insights into the role of apoE4 in disease pathogenesis. Toward this end, we evaluated the effect of the L28P mutation on the structural and functional properties of apoE4. ApoE4[L28P] was found to have significantly perturbed thermodynamic properties, to have reduced helical content, and to expose a larger portion of the hydrophobic surface to the solvent. Furthermore, this mutant is thermodynamically destabilized and more prone to proteolysis. When interacting with lipids, apoE4[L28P] formed populations of lipoprotein particles with structural defects. The structural perturbations brought about by the mutation were accompanied by aberrant functions associated with the pathogenesis of AD. Specifically, apoE4[L28P] promoted the cellular uptake of extracellular amyloid β peptide 42 (Aβ42) by human neuroblastoma SK-N-SH cells as well as by primary mouse neuronal cells and led to increased formation of intracellular reactive oxygen species that persisted for at least 24 h. Furthermore, lipoprotein particles containing apoE4[L28P] induced intracellular reactive oxygen species formation and reduced SK-N-SH cell viability. Overall, our findings suggest that the L28P mutation leads to significant structural and conformational perturbations in apoE4 and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress. We propose that these structural and functional changes underlie the observed added risk for AD development in carriers of apoE4[L28P].

  8. [Cohort study on the prevalence and risk factors of late pulmonary complications in adults following a closed minor chest trauma].

    Science.gov (United States)

    Plourde, Miville; Émond, Marcel; Lavoie, André; Guimont, Chantal; Le Sage, Natalie; Chauny, Jean-Marc; Bergeron, Éric; Vanier, Laurent; Moore, Lynne; Allain-Boulé, Nadine; Fratu, Ramona-Florina; Dufresne, Maryline

    2013-11-01

    The objectives of this study are to determine the prevalence, risk factors, and time to onset of delayed hemothorax and pneumothorax in adults who experienced a minor blunt thoracic trauma. A prospective cohort of 450 consecutive patients was recruited. Eligible patients had to be over 16 years of age, consulted within 72 hours for a trauma, and available for outpatient follow-up at 2, 7, and 14 days posttrauma. The clinical outcome investigated was the presence of delayed pneumothorax or hemothorax on the follow-up chest x-ray. Delayed hemothorax occurred in 11.8% (95% CI 8.8-14.8), and delayed pneumothorax occurred in 0.9% (95% CI 0.2-2.3) of participants. During the 14-day follow-up period, 87.0% of these delayed complications developed in the first week. In the multivariate analysis, the only statistically significant risk factor for delayed complications was the location of fractures on the x-ray of the hemithorax. The adjusted odds ratio was 1.52 (95% CI 0.62-3.73) for the lower ribs (tenth to twelfth rib), 3.11 (95% CI 1.60-6.08) for the midline ribs (sixth to ninth rib), and 5.05 (95% CI 1.80-14.19) for the upper ribs (third to fifth rib) versus patients with no fractures. The presence of at least one rib fracture between the third and ninth rib on the x-ray of the hemithorax is a significant risk factor for delayed hemothorax and pneumothorax.

  9. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

    Science.gov (United States)

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

    2016-02-25

    Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Maternal Vitamin D Status in the Late Second Trimester and the Risk of Severe Preeclampsia in Southeastern China

    Directory of Open Access Journals (Sweden)

    Xin Zhao

    2017-02-01

    Full Text Available The association between maternal vitamin D deficiency and the risk of severe preeclampsia is still debated. In the present study, we aimed to evaluate vitamin D status in Chinese pregnant women and investigate its correlation with the odds of developing severe preeclampsia. A cohort study was performed on 13,806 pregnant women who routinely visited the antenatal care clinics and subsequently delivered at the Wuxi Maternity and Child Health Hospital. All the subjects in the cohort had their serum 25-hydroxyvitamin D (25(OHD concentrations measured during pregnancy. A high prevalence of maternal vitamin D deficiency (25(OHD < 50 nmol/L was found. Pregnant women who had different BMIs before pregnancy had significantly different serum concentrations of 25(OHD. There was also a significant difference in the serum 25(OHD concentration among pregnant women of different ages. The serum 25(OHD concentration was significantly lower in pregnant women who subsequently developed severe preeclampsia compared with those who did not. Maternal vitamin D deficiency at 23–28 weeks of gestation was strongly associated with increased odds for severe preeclampsia after adjusting for relevant confounders (adjusted OR, 3.16; 95% CI, 1.77–5.65. Further studies are required to investigate whether vitamin D supplementation would reduce the risk of severe preeclampsia and improve pregnancy outcomes.

  11. Phantom limb pain: a case of maladaptive CNS plasticity?

    DEFF Research Database (Denmark)

    Flor, Herta; Nikolajsen, Lone; Jensen, Troels Staehelin

    2006-01-01

    might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human...

  12. Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report

    NARCIS (Netherlands)

    S. Grisariu (Sigal); B. Avni (Batia); T.T. Batchelor (Tracy); M.J. van den Bent (Martin); F. Bokstein (Felix); D. Schiff (David); O. Kuittinen (Outi); M.C. Chamberlain (Marc C.); P. Roth (Patrick); A. Nemets (Anatoly); E. Shalom (Edna); D. Ben-Yehuda (Dina); T. Siegal (Tali)

    2010-01-01

    textabstractNeurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%.

  13. Causes of CNS inflammation and potential targets for anticonvulsants.

    Science.gov (United States)

    Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos

    2013-08-01

    Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

  14. Metallothionein Expression and Roles During Neuropathology in the CNS

    DEFF Research Database (Denmark)

    Penkowa, Milena

    2006-01-01

    , their receptors and neurotrophins (TGFb, TGFb-Receptor, bFGF, bFGF-Receptor, VEGF, NT-3, NT-4/5, NGF); angiogenesis; and growth cone formation. Hence, MT-I+II enhance CNS tissue repair as seen clearly after the cryogenic injury, after which MT-I+II promote substitution of the necrotic lesion cavity with a glial...

  15. Glypicans and FGFs in CNS Development and Function

    NARCIS (Netherlands)

    Galli, Antonella

    2003-01-01

    One of the most important events during central nervous system (CNS) development is the communication between cells. Cell-to-cell signaling implicates the interaction between a signaling molecules (or ligands) and their receptors. Ligand-receptor interaction is a tightly regulated process and is

  16. Problems of prophylactic CNS radiotherapy in acute children's leukemia

    International Nuclear Information System (INIS)

    Bek, V.; Pribylova, O.; Abrahamova, J.; Hynieova, H.; Hrodek, O.

    1980-01-01

    The prophylactic treatment of the CNS was conducted by cobalt teletherapy of the cranium and by intrathecal application of MTX after the induction of primary remission in 70 children with acute leukemia throughout 5 years up to the end of 1978. The method of the combined radio- and chemoprophylaxis of the CNS was being changed during the years, especially as far as the radiation dose for the cranium was concerned. A detailed analysis made in a group of 59 children with the minimum interval of 18 months from the beginning of the treatment showed the best results after the application of a dose of 24 Gy/3 weeks. Following this procedure the relapse of leukemia in the CNS occurred in 9% only, whereas on the application of doses of 20 Gy and lower it occurred in 35 to 40%. On the whole 24 out of 59 children, i.e. 41%, are surviving, 35 children, i.e. 59%, died. Mostly complete, but only temporary, epilation was an invariable consequence of the irradiation of the cranium. The somnolence syndrome was only sporadically observed. It cannot be excluded, however, that some of its forms in patients discharged from hospital escaped attention. No case was recorded of serious impairment of the CNS of the leukoencephalopathic type. Up to now the psychomotor, intellectual and emotional development of the surviving children has been normal. (author)

  17. CT of early and late posttraumatic brain lesions in evaluation of the risk of deterioration and prognosis of clinical outcome

    International Nuclear Information System (INIS)

    Ghanim, A.; Boguslawska, R.; Walecki, J.

    2003-01-01

    The authors analysed Traumatic Coma Data Bank (TCDB) based on the initial posttraumatic brain computerized tomography findings (CT) using the Marshall's classification. It utilizes the status of the mesencephalic cisterns, the degree of medline shift and the presence or absence of one or more surgical masses. This classification allows us to assess the risk of intracranial hypertension. 1. The prognostic value of computerized tomography in patients with head injuries based on TCDB (Marshall) classification. 2. The relationship between the CT findings and the clinical examination. 3. The evaluation of the patients condition one year after trauma. The paper summarized the outcome of 523 patients with head injuries, 383 male (73.23%) and 140 female (26.77%), who underwent the initial CT scan in the first 48 hours after the injury. The age of the patients ranged from 17 to 88 years, the mean age for male was 42.86-18.72 years, and for female 47-19.22 years. The Glasgow Coma Scale was used at admission to hospital. The general condition of patients and the results of therapy were different in each category. 221 patients (42.26%) underwent surgery and 302 (57.74%) were treated medically. The highest mortality and complication rate was observed in categories III, IV and VII. The risk of mortality rate was higher in older group (age >40 years), chi2=0.528; p 0.0001). Except for localization and volume of the changes, the outcome of patients with head injuries depends on the cistern condition. The compression of cisterns menaces the secondary brainstem damage. The clinical outcome one year after the injury resembled CT scan findings in all categories. (author)

  18. Fertility preservation in women with CNS tumors.

    Science.gov (United States)

    Tosoni, Alicia; Balestrini, Damiano; Brandes, Alba A

    2017-05-01

    Fertility impairment due to treatments is a major concern for adolescents and young adult patients who survived cancer. Areas covered: Chemotherapy may determine a detrimental effect on ovary function, leading to infertility, and premature ovarian failure. Embryo and oocyte cryopreservation is a standard strategy for fertility preservation; other strategies, such as gonadal tissue cryopreservation and the use of gonadotropin - releasing hormone agonist, are still considered experimental. There are few data available regarding the effect of pregnancy on glioma, which indicates tumor progression during pregnancy in 33-45% of patients. Expert commentary: Glioma patients need to be advised about the risk of tumor progression during pregnancy, and about the possible, even if not proven, interaction between hormone stimulation and tumor growth.

  19. Late somatic effects

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1989-01-01

    Late effects are by definition effects that occur at least one year, and in most cases decades, after the time of exposure. The late effects considered in this chapter are limited to latent cancer incidence and mortality, and benign thyroid disease. A model is provided for estimating risks of late effects resulting from the radiation exposure likely to be received in the event of a nuclear power plant accident. It is assumed that exposure to high-LET radiation would be negligible in such an accident, and thus only risks from low-LET exposure are evaluated. Separate estimates are provided for risks of leukemia, bone cancer, lung cancer, gastrointestinal cancers, thyroid cancer, skin cancer, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. Because the time of death is also important in assessing the impact of an accident, and because the quality of life after the occurrence of cancer will often be reduced, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated

  20. Información sobre las secuelas y futuros riesgos para los sobrevivientes de retinoblastoma Information on late effects and future risks for retinoblastoma survivors

    Directory of Open Access Journals (Sweden)

    Laura Schwartz

    2005-04-01

    Full Text Available Los índices de sobrevida de los pacientes con cáncer en la infancia han aumentado en las últimas décadas. Se observan secuelas como consecuencia de esta enfermedad y su tratamiento. Los sobrevivientes de retinoblastoma presentan efectos adversos como consecuencia de la cirugía, la radioterapia y la quimioterapia. Las formas bilaterales irradiadas presentan un riesgo aumentado de desarrollar un segundo cáncer. Tanto los casos que presentaron retinoblastoma unilateral o bilateral pueden transmitir esta enfermedad a su descendencia. El diagnóstico de este tumor es excepcional después de los 4 años de edad y no se sabe claramente qué conocimiento tienen estos sobrevivientes del diagnóstico, del tratamiento y de los futuros riesgos. El consentimiento informado y el posterior resumen de historia clínica no aclaran demasiado a los padres. Los pacientes curados de retinoblastoma se verían beneficiados con un seguimiento prolongado en las instituciones en que fueron tratados, ya que les permitiría recibir información acerca de lo padecido, del tratamiento, de los riesgos y se podrían identificar las consecuencias posteriores de la enfermedad y su tratamiento.The survival rates of childhood cancer have increased in the past few decades. Late consequences related to the cancer and the treatment are observed. The late effects in retinoblastoma survivors are related to the surgery, the radiotherapy and the chemotherapy. Patients with irradiated bilateral retinoblastoma are at high risk to develop a second cancer. Survivors of bilateral or unilateral forms could transmit this disease to their offspring. The diagnosis of retinoblastoma is exceptional after 4 years of age, and it is not clear whether these survivors have knowledge of their diagnosis, treatment and future risks. The informed consent and the summary of the clinical histories do not help to clarify the situation. It will be of great benefit for the patients cured of retinoblastoma

  1. Early-versus Late-Onset Alzheimer Disease: Long-Term Functional Outcomes, Nursing Home Placement, and Risk Factors for Rate of Progression.

    Science.gov (United States)

    Wattmo, Carina; Wallin, Åsa K

    2017-01-01

    Whether age at onset influences functional deterioration in Alzheimer disease (AD) is unclear. We, therefore, investigated risk factors for progression in activities of daily living (ADL) and nursing home placement (NHP) in cholinesterase inhibitor (ChEI)-treated patients with early-onset AD (EOAD) versus late-onset AD (LOAD). This 3-year, prospective, observational, multicenter study included 1,017 participants with mild-to-moderate AD; 143 had EOAD (onset factors that could affect functional outcome and NHP were analyzed using mixed-effects models and logistic regression, respectively. Younger individuals exhibited longer illness duration before AD diagnosis, whereas 6-month functional response to ChEI therapy, 3-year changes in ADL capacities, time from diagnosis to NHP, and survival time in nursing homes were similar between the groups. In LOAD, a higher ChEI dose, no antidepressant use, and lower education level were protective factors for slower instrumental ADL (IADL) decline. In EOAD, antihypertensives/cardiac therapy implied faster IADL progression but lower risk of NHP. This study highlights the clinical importance of an earlier diagnosis and treatment initiation and the need for functional evaluations in EOAD. Despite the age differences between EOAD and LOAD, a similar need for nursing homes was observed.

  2. Early- versus Late-Onset Alzheimer Disease: Long-Term Functional Outcomes, Nursing Home Placement, and Risk Factors for Rate of Progression

    Directory of Open Access Journals (Sweden)

    Carina Wattmo

    2017-05-01

    Full Text Available Background/Aims: Whether age at onset influences functional deterioration in Alzheimer disease (AD is unclear. We, therefore, investigated risk factors for progression in activities of daily living (ADL and nursing home placement (NHP in cholinesterase inhibitor (ChEI-treated patients with early-onset AD (EOAD versus late-onset AD (LOAD. Methods: This 3-year, prospective, observational, multicenter study included 1,017 participants with mild-to-moderate AD; 143 had EOAD (onset <65 years and 874 LOAD (onset ≥65 years. Possible sociodemographic and clinical factors that could affect functional outcome and NHP were analyzed using mixed-effects models and logistic regression, respectively. Results: Younger individuals exhibited longer illness duration before AD diagnosis, whereas 6-month functional response to ChEI therapy, 3-year changes in ADL capacities, time from diagnosis to NHP, and survival time in nursing homes were similar between the groups. In LOAD, a higher ChEI dose, no antidepressant use, and lower education level were protective factors for slower instrumental ADL (IADL decline. In EOAD, antihypertensives/cardiac therapy implied faster IADL progression but lower risk of NHP. Conclusion: This study highlights the clinical importance of an earlier diagnosis and treatment initiation and the need for functional evaluations in EOAD. Despite the age differences between EOAD and LOAD, a similar need for nursing homes was observed.

  3. NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Endocrine Challenges--Thyroid Dysfunction, Growth Impairment, Bone Health, & Reproductive Risks

    Science.gov (United States)

    Dvorak, Christopher C.; Gracia, Clarisa R.; Sanders, Jean E.; Cheng, Edward Y.; Baker, K. Scott; Pulsipher, Michael A.; Petryk, Anna

    2011-01-01

    The endocrine system is highly susceptible to damage by high-dose chemotherapy and/or irradiation prior to hematopoietic cell transplantation (HCT) during childhood. The specific endocrine organs most affected by HCT include the thyroid gland, the pituitary, and the gonads. In addition, hormones that support development and stability of the skeletal system are also affected. Insufficiency of thyroid hormone is one of the most common late sequelae of HCT, and occurs more often in young children. Deficiency in the pituitary’s production of growth hormone is a problem of unique concern to the pediatric population. The reproductive risks of HCT depend on the patient’s gender and pubertal status at the time of HCT. Pubertal or gonadal failure frequently occurs, especially in females. Infertility risks for both genders remain high, while methods of fertility preservation are limited in all but post-pubertal males. Bone health post-HCT can be compromised by low bone mineral density as well as avascular necrosis, but the data on both problems in the pediatric HCT population are limited. In this paper, the current state of knowledge, gaps in that knowledge, and recommendations for future research are addressed in detail for each of these systems. PMID:22005649

  4. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  5. Central nervous system medications and falls risk in men aged 60-75 years

    DEFF Research Database (Denmark)

    Masud, Tahir; Frost, Morten; Ryg, Jesper

    2013-01-01

    Introduction: drugs acting on the central nervous system (CNS) increase falls risk. Most data on CNS drugs and falls are in women/mixed-sex populations. This study assessed the relationship between CNS drugs and falls in men aged 60-75 years.......Introduction: drugs acting on the central nervous system (CNS) increase falls risk. Most data on CNS drugs and falls are in women/mixed-sex populations. This study assessed the relationship between CNS drugs and falls in men aged 60-75 years....

  6. Late Raphael

    OpenAIRE

    Henry, Tom F. K.; Joannides, Paul; González Mozo, Ana; Martín, Bruno

    2012-01-01

    Exhibition catalogue (co-authored with P. Joannides) in English, Spanish and French by the Museo del Prado and the Musée du Louvre, 2012. English edition, publisher: Museo Nacional del Prado (ISBN 978-84-8480-237-2). 382 pages, of which 300 were co-authored with P. Joannides. This publication was the catalogue of the major exhibtion of Raphael's late work which was at the Prado and the Louvre in 2012-13. The exhibition was seen by more than 650,000 visitors, and was widely reviewed in the int...

  7. Association of Late Adolescent Personality With Risk for Subsequent Serious Mental Illness Among Men in a Swedish Nationwide Cohort Study.

    Science.gov (United States)

    Hayes, Joseph F; Osborn, David P J; Lewis, Glyn; Dalman, Christina; Lundin, Andreas

    2017-07-01

    Understanding of personality as an independent risk factor for serious mental illness (SMI) remains limited. Recently, overlap between the polygenic basis for specific personality traits and specific SMIs has been identified. To determine the association of the adolescent personality domains of social maturity, mental energy, and emotional stability with later diagnosis of SMI. This longitudinal cohort study enrolled Swedish male military conscripts aged 18 or 19 years from January 1, 1974, through December 31, 1997. The diagnosis of an SMI was extracted from the National Patient Register for all inpatient treatment episodes in Sweden from January 1, 1974, through December 31, 2011. Data were analyzed from May 3 to September 16, 2016. Social maturity, mental energy, and emotional stability assessed at conscription interview. Inpatient diagnoses of bipolar disorder, schizoaffective disorder, schizophrenia, and other nonaffective psychoses occurring until December 31, 2011. Of the 1 017 691 men included in the cohort, 4310 developed bipolar disorder; 784, schizoaffective disorder; 4823, schizophrenia; and 5013, other nonaffective psychoses. After adjustment, with use of mean scores as a reference, low social maturity (hazard ratio [HR], 1.61; 95% CI, 1.48-1.74), low mental energy (HR, 1.34; 95% CI, 1.24-1.44), and low emotional stability (HR, 1.51; 95% CI, 1.40-1.63) were inversely associated with schizophrenia in a dose-dependent fashion. Other nonaffective psychoses displayed a similar pattern. Bipolar disorder was associated with high (HR, 1.21; 95% CI, 1.09-1.35) and low (HR, 1.12; 95% CI, 1.01-1.25) social maturity and low emotional stability (HR, 1.62; 95% CI, 1.46-1.78). Schizoaffective disorder was associated with low emotional stability (HR, 1.53; 95% CI, 1.26-1.85). Emotional stability is inversely associated with all SMI. Bipolar disorder has a unique U-shaped association with social maturity. Premorbid personality may reflect subtle changes in

  8. The shifting landscape of metastatic breast cancer to the CNS.

    Science.gov (United States)

    Quigley, Matthew R; Fukui, Olivia; Chew, Brandon; Bhatia, Sanjay; Karlovits, Steven

    2013-07-01

    The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1-4 (p = .004, log-rank), which

  9. Respective impact of implementation of prevention strategies, colonization with multiresistant bacteria and antimicrobial use on the risk of early- and late-onset VAP: An analysis of the OUTCOMEREA network

    OpenAIRE

    Ibn Saied, Wafa; Souweine, Bertrand; Garrouste-Orgeas, Maité; Ruckly, Stéphane; Darmon, Michael; Bailly, Sébastien; Cohen, Yves; Azoulay, Elie; Schwebel, Carole; Radjou, Aguila; Kallel, Hatem; Adrie, Christophe; Dumenil, Anne-Sylvie; Argaud, Laurent; Marcotte, Guillaume

    2017-01-01

    International audience; Rationale: The impact of prevention strategies and risk factors for early-onset (EOP) versus late-onset (LOP) ventilator -associated pneumonia (VAP) are still debated.Objectives: To evaluate, in a multicenter cohort, the risk factors for EOP and LOP, as the evolution of prevention strategies.Methods: 7,784 patients with mechanical ventilation (MV) for at least 48 hours were selected into the multicenter prospective OUTCOMEREA database (1997-2016). VAP occurring between...

  10. Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; Kokki, Hannu; Kokki, Merja; Danhof, Meindert; van Hasselt, Johan G. C.; de Lange, Elizabeth C. M.

    2018-01-01

    Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human,

  11. Tendencies the treatment of the central nervous system (CNS) tumors

    International Nuclear Information System (INIS)

    Alert Silva, Jose; Jimenez Medina, Jose

    2004-01-01

    It is known that the treatment of the central nervous system (CNS) tumors is based on the use of surgery and radiotherapy (RT) and that chemotherapy (QMT) is used even more, as well as the other drugs. A bibliographic review was made to update the knowledge on the current trends and perspectives of RT applied to CNS tumors. The following were found among them: a) combinations of RT and CMT; b) radiosensitizers incorporated to the radiant treatment; c) angiogenesis inhibitors associated with RT; d) the scale-up or increase of the RT doses thanks to the development of new technologies, such as 3 D conformal radiotherapy, intensity- modulated radiotherapy, surgery and others. Another field of research is that of the changes in the rhythm or fractioning of the RT: hyperfractionated, accelerated, combinations of both, etc., which will allow mainly to increase the dosage scale-up

  12. CNS-targets in control of energy and glucose homeostasis.

    Science.gov (United States)

    Kleinridders, André; Könner, A Christine; Brüning, Jens C

    2009-12-01

    The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

  13. Disruption of the blood-brain barrier as the primary effect of CNS irradiation.

    Science.gov (United States)

    Rubin, P; Gash, D M; Hansen, J T; Nelson, D F; Williams, J P

    1994-04-01

    The blood-brain barrier (BBB) is believed to be unique in organ microcirculation due to the 'tight junctions' which exist between endothelial cells and, some argue, the additional functional components represented by the perivascular boundary of neuroglial cells; these selectively exclude proteins and drugs from the brain parenchyma. This study was designed to examine the effects of irradiation on the BBB and determine the impact of the altered pathophysiology on the production of central nervous system (CNS) late effects such as demyelination, gliosis and necrosis. Rats, irradiated at 60 Gy, were serially sacrificed at 2, 6, 12 and 24 weeks. Magnetic resonance image analysis (MRI) was obtained prior to sacrifice with selected animals from each group. The remaining animals underwent horse-radish peroxidase (HRP) perfusion at the time of sacrifice. The serial studies showed a detectable disruption of the BBB at 2 weeks post-irradiation and this was manifested as discrete leakage; late injury seen at 24 weeks indicated diffuse vasculature leakage, severe loss of the capillary network, cortical atrophy and white matter necrosis. Reversal or repair of radiation injury was seen between 6 and 12 weeks, indicating a bimodal peak in events. Blood-brain barrier disruption is an early, readily recognizable pathophysiological event occurring after radiation injury, is detectable in vivo/in vitro by MRI and HRP studies, and appears to precede white matter necrosis. Dose response studies over a wide range of doses, utilizing both external and interstitial irradiation, are in progress along with correlative histopathologic and ultrastructural studies.

  14. 4th ENRI International Workshop on ATM/CNS

    CERN Document Server

    2017-01-01

    This book is a compilation of selected papers from the 4th ENRI International Workshop on ATM/CNS (EIWAC2015). The work focuses on novel techniques for aviation infrastructure in air traffic management (ATM) and communications, navigation, surveillance, and informatics (CNSI) domains. The contents make valuable contributions to academic researchers, engineers in the industry, and regulators of aviation authorities. As well, readers will encounter new ideas for realizing a more efficient and safer aviation system. .

  15. Morphological evaluation of fetus CNS and its related anomalies

    International Nuclear Information System (INIS)

    Oi, Shizuo; Tamaki, Norihiko; Matsumoto, Satoshi; Katayama, Kazuaki; Mochizuki, Matsuto

    1989-01-01

    The fetus central nervous system was evaluated morphologically by ultrasonography (US), magnetic resonance imaging (MRI), and CT scan to analyze the prenatal diagnostic value for CNS anomalies. A total of 31 patients with 42 lesions had been diagnosed during the preceding 7 years. The patients included 24 with hydrocephalus, three with anencephaly, three with myeloschisis, three with holoprosencephaly, three with an encephalocele, two with a Dandy-Walker cyst, one with hydroencephalodysplasia, one with an intracranial neoplasm, one with sacrococcygeal teratoma, and one with sacral agenesis. Compared with US and MRI, CT proved to be more accurate in the detection of spine and cranium-bone morphology. This finding seems to be valuable in the diagnosis of spina bifida, cranium bifidum and some cases of hypertensive hydrocephalus, especially in the axial view. MRI was definitely superior in the anatomico-pathological diagnosis of cerebral dysgenesis, ventriculomegaly, intracranial tumors, and other brain parenchymal changes in view of multi-dimensional analysis. The most considerable disadvantage of MRI in the diagnosis of a fetus CNS anomaly is the poor information about spine and cranium morphology. A super-conducting MRI system is still insufficient to demonstrate the spinal cord of a fetus. US was routinely used, and the multidimensional slices were useful for screening the CNS abnormalies. Some of the fetus brain lesions, such as intracranial hematomas, had a specific echogenecity on US. However, US sometimes failed to demarcate the cerebral parenchymal or subdural morphological changes because its artifacts had hyperchoic shadows. While US, MRI, and CT were valuable diagnostic tools in the morphological evaluation of fetus CNS and its related anomalies, each modality has different diagnostic advantages and disadvantages. Improvement can be expected when these diagnostic imaging modalities are complementary, depending upon the nature of the anatomy. (J.P.N.)

  16. Primary CNS lymphoma in nonimmunocompromised patients magnetic resonance study

    International Nuclear Information System (INIS)

    Pena, J.; Fernandez, J.M.; Galarraga, M.I.; Pozo, A.; Montes, A.; Ablanedo, P.

    1995-01-01

    Prymary lymphoma of the CNS (PLCNS) is a relatively infrequent malignant tumor that has become increasingly common over the past decade. The radiological signs, although not pathognomonic, are quite specific and suggestive of the correct diagnosis, thus facilitating therapeutic management. We present six cases of PLCNS in nonimmunocopromised patients studied by MR in our hospital over the past two and a half years. We describe theradiological findings, correlating them with those mentioned in the literature. 14 refs

  17. Computerized tomography data on CNS affection in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Ivanova, M.M.; Bliznyuk, O.I.; Todua, F.I.; Tumanova, A.A.

    1989-01-01

    Computed tomography (CT) of the brain was employed in 40 patients with systemic lupus erythematosus (SLE). Clinical cerebral pathology was obvious in 30 and absent in 10 patients. By CT cerebral symptoms were divided of 4 groups. Clinical symptom complexes of CNS defects and SLE were reflected on definite CT images correlated with focal damage to the brain. CT picture of enlarged subarachnoid space, ventricles and basal cisterns can be observed in SLE patients without neurological symptoms. This indicated likely subclinical cerebral affection

  18. Risk determination after an acute myocardial infarction: review of 3 clinical risk prediction tools.

    Science.gov (United States)

    Scruth, Elizabeth Ann; Page, Karen; Cheng, Eugene; Campbell, Michelle; Worrall-Carter, Linda

    2012-01-01

    The objective of the study was to provide comprehensive information for the clinical nurse specialist (CNS) on commonly used clinical prediction (risk assessment) tools used to estimate risk of a secondary cardiac or noncardiac event and mortality in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). The evolution and widespread adoption of primary PCI represent major advances in the treatment of acute myocardial infarction, specifically STEMI. The American College of Cardiology and the American Heart Association have recommended early risk stratification for patients presenting with acute coronary syndromes using several clinical risk scores to identify patients' mortality and secondary event risk after PCI. Clinical nurse specialists are integral to any performance improvement strategy. Their knowledge and understandings of clinical prediction tools will be essential in carrying out important assessment, identifying and managing risk in patients who have sustained a STEMI, and enhancing discharge education including counseling on medications and lifestyle changes. Over the past 2 decades, risk scores have been developed from clinical trials to facilitate risk assessment. There are several risk scores that can be used to determine in-hospital and short-term survival. This article critiques the most common tools: the Thrombolytic in Myocardial Infarction risk score, the Global Registry of Acute Coronary Events risk score, and the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications risk score. The importance of incorporating risk screening assessment tools (that are important for clinical prediction models) to guide therapeutic management of patients cannot be underestimated. The ability to forecast secondary risk after a STEMI will assist in determining which patients would require the most aggressive level of treatment and monitoring postintervention including

  19. EMMPRIN, an upstream regulator of MMPs, in CNS biology.

    Science.gov (United States)

    Kaushik, Deepak Kumar; Hahn, Jennifer Nancy; Yong, V Wee

    2015-01-01

    Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction. Copyright © 2015 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  20. Mechanisms of CNS invasion and damage by parasites.

    Science.gov (United States)

    Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

    2013-01-01

    Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. CNS Involvement in Hemophagocytic Lymphohistiocytosis: CT and MR Findings

    International Nuclear Information System (INIS)

    Chung, Tae Woong

    2007-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. emophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by nonmalignant diffuse infiltration of multiple organs, including the central nervous system (CNS), by lymphocytes and histiocytes (1). Many radiologic reports describing diffuse white matter infiltrations, parenchymal atrophy and calcification have been published, but the characteristics of these findings remain non-specific, especially in immunocompromised patients. We present here a case of HLH in a 3-year-old boy who presented with multiple ring enhancing lesions involving the brain. In conclusion, although the CT and MRI findings of HLH with ring enhancing parenchymal lesions are nonspecific and mimic abscess, and especially in the immunosuppressed patients, increased diffusion at the center on DWI may be a finding of HLH to differentiate it from abscess, which has restricted diffusion at the center. However, the pathologic correlation with DWI according to the lesion stage certainly needs further study with a larger number of patients

  2. Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy. Risk-modifying factors

    International Nuclear Information System (INIS)

    Hille-Betz, Ursula; Soergel, Philipp; Kundu, Sudip; Klapdor, Ruediger; Hillemanns, Peter; Vaske, Bernhard; Bremer, Michael; Henkenberens, Christoph

    2016-01-01

    The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters. (orig.) [de

  3. Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ε4, and the Risk of Late-Onset Alzheimer Disease in African Americans

    Science.gov (United States)

    Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hendrie, Hugh; Hall, Kathleen S.; Goate, Alison M.; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Mayeux, Richard

    2013-01-01

    Importance Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, Setting, and Participants The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance–weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main Outcomes and Measures Presence of Alzheimer disease according to standardized criteria. Results Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10–9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8

  4. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.

    Science.gov (United States)

    Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B; Graff-Radford, Neill R; Evans, Denis; De Jager, Philip L; Crane, Paul K; Buxbaum, Joseph D; Murrell, Jill R; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T; Green, Robert C; Barnes, Lisa L; Cantwell, Laura B; Fallin, M Daniele; Go, Rodney C P; Griffith, Patrick; Obisesan, Thomas O; Manly, Jennifer J; Lunetta, Kathryn L; Kamboh, M Ilyas; Lopez, Oscar L; Bennett, David A; Hendrie, Hugh; Hall, Kathleen S; Goate, Alison M; Byrd, Goldie S; Kukull, Walter A; Foroud, Tatiana M; Haines, Jonathan L; Farrer, Lindsay A; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Mayeux, Richard

    2013-04-10

    Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. To identify genetic loci associated with late-onset Alzheimer disease in African Americans. The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Presence of Alzheimer disease according to standardized criteria. Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8 Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005 Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional

  5. Risk of Late Urinary Complications Following Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: Refining Bladder Dose-Volume Parameters.

    Science.gov (United States)

    Manea, Elena; Escande, Alexandre; Bockel, Sophie; Khettab, Mohamed; Dumas, Isabelle; Lazarescu, Ioana; Fumagalli, Ingrid; Morice, Philippe; Deutsch, Eric; Haie-Meder, Christine; Chargari, Cyrus

    2018-06-01

    To study correlations between dose-volume parameters of the whole bladder and bladder trigone and late urinary toxicity in locally advanced cervical cancer patients treated with pulsed-dose-rate brachytherapy. Patients with locally advanced cervical cancer treated with chemoradiation therapy and pulsed-dose-rate brachytherapy from 2004 to 2015 were included. Cumulative dose-volume parameters of the whole bladder and bladder trigone were converted into 2-Gy/fraction equivalents (EQD2, with α/β = 3 Gy); these parameters, as well as clinical factors, were analyzed as predictors of toxicity in patients without local relapse. A total of 297 patients fulfilled the inclusion criteria. The median follow-up period was 4.9 years (95% confidence interval 4.5-5.3 years). In patients without local relapse (n = 251), the Kaplan-Meier estimated grade 2 or higher urinary toxicity rates at 3 years and 5 years were 25.4% and 32.1%, respectively. Minimal dose to the most exposed 2 cm 3 of the whole bladder [Formula: see text] , bladder International Commission on Radiation Units & Measurements (ICRU) (B ICRU ) dose, and trigone dose-volume parameters correlated with grade 2 or higher toxicity. At 3 years, the cumulative incidence of grade 2 or higher complications was 22.8% (standard error, 2.9%) for bladder [Formula: see text]   60 Gy EQD2 was significant for grade 2 or higher toxicity (P = .027). The probability of grade 3 or higher toxicities increased with bladder [Formula: see text]  > 80 Gy EQD2 (16.7% vs 1.6%; hazard ratio [HR], 5.77; P = .039), B ICRU dose > 65 Gy EQD2 (4.9% vs 1.3%; HR, 6.36; P = .018), and trigone D 50%  > 60 Gy EQD2 (3.1% vs 1.2%; HR, 6.29; P = .028). Pearson correlation coefficients showed a moderate correlation between bladder [Formula: see text] , B ICRU dose, and bladder trigone D 50% (P < .0001). These data suggest that [Formula: see text]  ≤ 80 Gy EQD2 should be advised for minimizing the risk of severe urinary

  6. Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma

    International Nuclear Information System (INIS)

    Merchant, Thomas E.; Kiehna, Erin N.; Li Chenghong; Shukla, Hemant; Sengupta, Saikat; Xiong Xiaoping; Gajjar, Amar; Mulhern, Raymond K.

    2006-01-01

    Purpose: Model the effects of radiation dosimetry on IQ among pediatric patients with central nervous system (CNS) tumors. Methods and Materials: Pediatric patients with CNS embryonal tumors (n = 39) were prospectively evaluated with serial cognitive testing, before and after treatment with postoperative, risk-adapted craniospinal irradiation (CSI) and conformal primary-site irradiation, followed by chemotherapy. Differential dose-volume data for 5 brain volumes (total brain, supratentorial brain, infratentorial brain, and left and right temporal lobes) were correlated with IQ after surgery and at follow-up by use of linear regression. Results: When the dose distribution was partitioned into 2 levels, both had a significantly negative effect on longitudinal IQ across all 5 brain volumes. When the dose distribution was partitioned into 3 levels (low, medium, and high), exposure to the supratentorial brain appeared to have the most significant impact. For most models, each Gy of exposure had a similar effect on IQ decline, regardless of dose level. Conclusions: Our results suggest that radiation dosimetry data from 5 brain volumes can be used to predict decline in longitudinal IQ. Despite measures to reduce radiation dose and treatment volume, the volume that receives the highest dose continues to have the greatest effect, which supports current volume-reduction efforts

  7. Disability, body image and sports/physical activity in adult survivors of childhood CNS tumors: population-based outcomes from a cohort study

    NARCIS (Netherlands)

    Boman, Krister K.; Hörnquist, Lina; de Graaff, Lisanne; Rickardsson, Jenny; Lannering, Birgitta; Gustafsson, Göran

    2013-01-01

    Childhood CNS tumor survivors risk health and functional impairments that threaten normal psychological development and self-perception. This study investigated the extent to which health and functional ability predict adult survivors' body image (BI) and self-confidence regarding sports and

  8. Late somatic effects

    International Nuclear Information System (INIS)

    Gilbert, E.

    1985-01-01

    A model is provided for estimating risks of late effects resulting from low-LET radiation exposure likely to be received in the event of a nuclear power plant accident. Separate estimates are provided for risks of leukemia, cancers of the bones, lungs, gastrointestinal tract, thyroid, skin, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. In addition, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated. The model used in the earlier Reactor Safety Study has been modified to reflect additional epidemiological data and these changes are described in detail. 37 references, 1 figure, 13 tables

  9. Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants born small for gestational age: a large multicenter study from the German Neonatal Network.

    Science.gov (United States)

    Tröger, Birte; Göpel, Wolfgang; Faust, Kirstin; Müller, Thilo; Jorch, Gerhard; Felderhoff-Müser, Ursula; Gortner, Ludwig; Heitmann, Friedhelm; Hoehn, Thomas; Kribs, Angela; Laux, Reinhard; Roll, Claudia; Emeis, Michael; Mögel, Michael; Siegel, Jens; Vochem, Matthias; von der Wense, Axel; Wieg, Christian; Herting, Egbert; Härtel, Christoph

    2014-03-01

    It was the aim of this study to assess whether very-low-birth-weight (VLBW) infants born small for gestational age (SGA; birth weight less than 10th percentile) are at increased risk for late-onset sepsis. This was a prospective, multicenter study of the German Neonatal Network including VLBW infants from 23 to risk with coagulase-negative staphylococci in our SGA cohort. In a multivariate logistic regression analysis, higher gestational age [per week; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.72-0.78, PGerman descendance (OR: 0.76, 95% CI: 0.63-0.91, P = 0.003) and prophylaxis with glycopeptide antibiotics (OR: 0.64, 95% CI: 0.47-0.87, P = 0.005) were shown to be protective against late-onset sepsis. In contrast, longer duration of parenteral nutrition (per day; OR: 1.016, 95% CI: 1.011-1.021, P risk factors (OR: 1.31, 95% CI: 1.02-1.68, P= 0.03). SGA contributes to the risk of late-onset sepsis in VLBW infants. Future studies are needed to investigate the underlying pathophysiology to guide individualized preventive measures in this vulnerable subgroup.

  10. Poor Vitamin C Status Late in Pregnancy Is Associated with Increased Risk of Complications in Type 1 Diabetic Women: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Bente Juhl

    2017-02-01

    Full Text Available Vitamin C (vitC is essential for normal pregnancy and fetal development and poor vitC status has been related to complications of pregnancy. We have previously shown lower vitC status in diabetic women throughout pregnancy compared to that of non-diabetic controls. Here, we evaluate the relationship between vitC status late in diabetic pregnancy in relation to fetal outcome, complications of pregnancy, diabetic characteristics, and glycemic control based on data of 47 women from the same cohort. We found a significant relationship between the maternal vitC level > or ≤ the 50% percentile of 26.6 μmol/L, respectively, and the umbilical cord blood vitC level (mean (SD: 101.0 μmol/L (16.6 versus 78.5 μmol/L (27.8, p = 0.02; n = 12/16, while no relation to birth weight or Apgar score was observed. Diabetic women with complications of pregnancy had significantly lower vitC levels compared to the women without complications (mean (SD: 24.2 μmol/L (10.6 vs. 34.6 μmol/L (14.4, p = 0.01; n = 19 and 28, respectively and the subgroup of women (about 28% characterized by hypovitaminosis C (<23 μmol/L had an increased relative risk of complications of pregnancy that was 2.4 fold higher than the one found in the group of women with a vitC status above this level (p = 0.02, 95% confidence interval 1.2–4.4. No correlation between diabetic characteristics of the pregnant women and vitC status was observed, while a negative association of maternal vitC with HbA1c at delivery was found at regression analysis (r = −0.39, p < 0.01, n = 46. In conclusion, our results may suggest that hypovitaminosis C in diabetic women is associated with increased risk of complications of pregnancy.

  11. Late Gadolinium Enhancement Amount as an Independent Risk Factor for the Incidence of Adverse Cardiovascular Events in Patients with Stage C or D Heart Failure

    Directory of Open Access Journals (Sweden)

    Tong Liu

    2016-10-01

    Full Text Available Background Myocardial fibrosis (MF is a risk factor for poor prognosis in dilated cardiomyopathy (DCM. Late gadolinium enhancement (LGE of the myocardium on cardiac magnetic resonance (CMR represents MF. We examined whether the LGE amount increases the incidence of adverse cardiovascular events in patients with stage C or D heart failure (HF. Methods Eighty-four consecutive patients with stage C or D HF, either ischemic or non-ischemic, were enrolled. Comprehensive clinical and CMR evaluations were performed. All patients were followed up for a composite endpoint of cardiovascular death, heart transplantation, and cardiac resynchronization therapy with defibrillator (CRT-D.Results LGE was present in 79.7% of the end-stage HF patients. LGE distribution patterns were mid-wall, epi-myocardial, endo-myocardial, and the morphological patterns were patchy, transmural, and diffuse. During the average follow-up of 544 days, 13 (15.5% patients had endpoint events: 7 patients cardiac death, 2 patients heart transplantation, and 4 patients underwent CRT-D implantation. On univariate analysis, LGE quantification on cardiac magnetic resonance, blood urine nitrogen, QRS duration on electrocardiogram, left ventricular end-diastolic diameter (LVEDD and left ventricular end-diastolic volume (LVEDV on CMR had the strongest associations with the composite endpoint events. However, on multivariate analysis for both Model I (after adjusting for age, sex, and body mass index and Model II (after adjusting for age, sex, BMI, renal function, QRS duration and atrial fibrillation on electrocardiogram, the etiology of HF, LVEF, CMR-LVEDD and CMR-LVEDV, LGE amount was a significant risk factor for composite endpoint events (Model I 6SD HR 1.037, 95%CI 1.005-1.071, p=0.022; Model II 6SD HR 1.045, 95%CI 1.001-1.084, p=0.022. Conclusion LGE amount from high-scale threshold on CMR increased the incidence of adverse cardiovascular events for patients in either stage C or D HF.

  12. A historical overview of probabilistic risk assessment development and its use in the nuclear power industry: a tribute to the late Professor Norman Carl Rasmussen

    International Nuclear Information System (INIS)

    Keller, William; Modarres, Mohammad

    2005-01-01

    This paper reviews the historical development of the probabilistic risk assessment (PRA) methods and applications in the nuclear industry. A review of nuclear safety and regulatory developments in the early days of nuclear power in the United States has been presented. It is argued that due to technical difficulties for measuring and characterizing uncertainties and concerns over legal challenges, safety design and regulation of nuclear power plants has primarily relied upon conservative safety assessment methods derived based on a set of design and safety principles. Further, it is noted that the conservatism adopted in safety and design assessments has allowed the use of deterministic performance assessment methods. This approach worked successfully in the early years of nuclear power epoch as the reactor design proved to be safe enough. However, it has been observed that as the conservative approach to design and safety criteria proved arbitrary, and yielded inconsistencies in the degree to which different safety measures in nuclear power plants protect safety and public heath, the urge for a more consistent assessment of safety became apparent in the late 1960s. In the early 1970s, as a result of public and political pressures, then the US Atomic Energy Commission initiated a new look at the safety of the nuclear power plants through a comprehensive study called 'Reactor Safety Study' (WASH-1400, or 'Rasmussen Study'-after its charismatic study leader Professor Norman Rasmussen of MIT) to demonstrate safety of the nuclear power plants. Completed in October 1975, this landmark study introduced a novel probabilistic, systematic and holistic approach to the assessment of safety, which ultimately resulted in a sweeping paradigm shift in safety design and regulation of nuclear power in the United States in the turn of the Century. Technical issues of historic significance and concerns raised by the subsequent reviews of the Rasmussen Study have been discussed

  13. Increased risk of antidepressant use in childhood cancer survivors

    DEFF Research Database (Denmark)

    Lund, Lasse Wegener; Winther, J.F.; Cederkvist, L

    2015-01-01

    to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer......AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage....... Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk...

  14. Early and late motherhood

    DEFF Research Database (Denmark)

    Christoffersen, Mogens; Lausten, Mette

    2009-01-01

    The study investigates parental child rearing methods, structural factors relating to the family during adolescence geographic segregation, individual resource deficits and social background of first time late live births among 32 to 37 years old women and compare to teenagers before becoming...... economic and social gradient for first-time teenage mothers. Teenagers who had experienced family separation or who were formerly in out-of-home care in particular had an increased risk of early childbearing. Results showed that teenage mothers were in every respect in a more disadvantaged position than...

  15. Immune and inflammatory responses in the CNS : Modulation by astrocytes

    DEFF Research Database (Denmark)

    Penkowa, Milena; aschner, michael; hidalgo, juan

    2008-01-01

    Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

  16. Kynurenines in CNS disease: regulation by inflammatory cytokines

    Science.gov (United States)

    Campbell, Brian M.; Charych, Erik; Lee, Anna W.; Möller, Thomas

    2014-01-01

    The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the “neurotoxic” and “neuroprotective” arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders. PMID:24567701

  17. Exploring Late Globalization

    DEFF Research Database (Denmark)

    Turcan, Romeo V.

    2016-01-01

    literature on late globalization from sociocultural and economic perspectives. It illustrates in a vignette the character and features of late globalization observable in the withdrawal from foreign locations or deinternationalization of universities, as late globalizing entitis. The paper discusses...

  18. Neurotransmitter synthesis from CNS glutamine for central control of breathing

    International Nuclear Information System (INIS)

    Hoop, B.; Systrom, D.; Chiang, C.H.; Shih, V.E.; Kazemi, H.

    1986-01-01

    The maximum rate at which CNS glutamine (GLN) derived from glutamate (GLU) can be sequestered for synthesis of neurotransmitter GLU and/or γ-aminobutyric acid (GABA) has been determined in pentobarbital-anesthetized dogs. A total of 57 animals were studied under normal, hypoxic (Pa/sub O2/ greater than or equal to 20 mmHg), or hypercapnic (Pa/sub CO2/ less than or equal to 71 mm Hg) conditions. Thirteen of these were bilaterally vagotomized and carotid body denervated and studied only under normoxic or hypoxic conditions. In 5 animals cerebrospinal fluid GLN transfer rate constant k was measured using 13 N-ammonia tracer. Measured cerebral cortical (CC) and medullary (MED) GLN concentrations c are found to vary with GLU metabolic rate r according to c-C/sub m/r/(r+R), where r, the product of k and corresponding tissue GLU concentration, is assumed equal to the maximum GLN metabolic rate via pathways other than for neurotransmitter synthesis. The constants C/sub m/ and R are the predicted maximum GLN concentration and its maximum rate of sequestration for neurotransmitter synthesis, respectively. For both CNS tissue types in all animals, C/sub m/ = 20.9 +- 7.4 (SD) mmoles/kg wet wt(mM) and R = 6.2 +- 2.3 mM/min. These values are consistent with results obtained in anesthetized rats

  19. Primary CNS lymphoma as a cause of Korsakoff syndrome.

    Science.gov (United States)

    Toth, Cory; Voll, Chris; Macaulay, Robert

    2002-01-01

    Korsakoff syndrome presents with memory dysfunction with retrograde amnesia, anterograde amnesia, limited insight into dysfunction, and confabulation. The most common etiology of Korsakoff syndrome is thiamine deficiency secondary to alcoholism. There are limited case reports of structural lesions causing Korsakoff syndrome. A 46-year-old male with a long history of alcoholism presented with a history of confusion, amnesia, and confabulation with no localizing features on neurological examination. The patient showed no clinical change with intravenous thiamine. Computed tomography of the brain revealed a heterogenous, enhancing mass lesion centered within the third ventricle, with other lesions found throughout cortical and subcortical regions. The patient was given dexamethasone i.v. without noticeable clinical improvement but with marked radiological improvement with mass reduction. Stereotactic biopsy revealed a diagnosis of primary central nervous system (CNS) lymphoma. Most patients presenting with Korsakoff syndrome have thiamine deficiency; however, mass lesions can produce an identical clinical picture. This is the first case report of a patient with primary CNS lymphoma presenting as Korsakoff syndrome.

  20. Glibenclamide for the Treatment of Acute CNS Injury

    Directory of Open Access Journals (Sweden)

    J. Marc Simard

    2013-10-01

    Full Text Available First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis—all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options.

  1. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    Science.gov (United States)

    Delishaj, Durim; Fabrini, Maria Grazia; Gonnelli, Alessandra; Morganti, Riccardo; Perrone, Franco; Tana, Roberta; Paiar, Fabiola; Gadducci, Angiolo

    2016-01-01

    Purpose The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). Material and methods Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity. PMID:28115957

  2. Gut-derived factors promote neurogenesis of CNS-neural stem cells and nudge their differentiation to an enteric-like neuronal phenotype.

    Science.gov (United States)

    Kulkarni, Subhash; Zou, Bende; Hanson, Jesse; Micci, Maria-Adelaide; Tiwari, Gunjan; Becker, Laren; Kaiser, Martin; Xie, Xinmin Simon; Pasricha, Pankaj Jay

    2011-10-01

    Recent studies have explored the potential of central nervous system-derived neural stem cells (CNS-NSC) to repopulate the enteric nervous system. However, the exact phenotypic fate of gut-transplanted CNS-NSC has not been characterized. The aim of this study was to investigate the effect of the gut microenvironment on phenotypic fate of CNS-NSC in vitro. With the use of Transwell culture, differentiation of mouse embryonic CNS-NSC was studied when cocultured without direct contact with mouse intestinal longitudinal muscle-myenteric plexus preparations (LM-MP) compared with control noncocultured cells, in a differentiating medium. Differentiated cells were analyzed by immunocytochemistry and quantitative RT-PCR to assess the expression of specific markers and by whole cell patch-clamp studies for functional characterization of their phenotype. We found that LM-MP cocultured cells had a significant increase in the numbers of cells that were immune reactive against the panneuronal marker β-tubulin, neurotransmitters neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and neuropeptide vasoactive intestinal peptide (VIP) and showed an increase in expression of these genes, compared with control cells. Whole cell patch-clamp analysis showed that coculture with LM-MP decreases cell excitability and reduces voltage-gated Na(+) currents but significantly enhances A-current and late afterhyperpolarization (AHP) and increases the expression of the four AHP-generating Ca(2+)-dependent K(+) channel genes (KCNN), compared with control cells. In a separate experiment, differentiation of LM-MP cocultured CNS-NSC produced a significant increase in the numbers of cells that were immune reactive against the neurotransmitters nNOS, ChAT, and the neuropeptide VIP compared with CNS-NSC differentiated similarly in the presence of neonatal brain tissue. Our results show that the gut microenvironment induces CNS-NSC to produce neurons that share some of the

  3. Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture.

    Science.gov (United States)

    Kim, Euiseok J; Battiste, James; Nakagawa, Yasushi; Johnson, Jane E

    2008-08-01

    Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate-mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiating as evidenced by rapid migration out of germinal zones. Ascl1 lineage cells contribute to distinct cell types in each major brain division: the forebrain including the cerebral cortex, olfactory bulb, hippocampus, striatum, hypothalamus, and thalamic nuclei, the midbrain including superior and inferior colliculi, and the hindbrain including Purkinje and deep cerebellar nuclei cells and cells in the trigeminal sensory system. Ascl1 progenitor cells at early stages in each CNS region preferentially become neurons, and at late stages they become oligodendrocytes. In conclusion, Ascl1-expressing progenitor cells in the brain give rise to multiple, but not all, neuronal subtypes and oligodendrocytes depending on the temporal and spatial context, consistent with a broad role in neural differentiation with some subtype specification.

  4. Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C; Carrasco, J; Hidalgo, J

    2001-01-01

    Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein......-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression...

  5. Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

    Science.gov (United States)

    Swedberg, Michael D B

    2016-01-01

    Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

  6. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

    NARCIS (Netherlands)

    Mocroft, Amanda; Lundgren, Jens D.; Sabin, Miriam Lewis; Monforte, Antonella d'Arminio; Brockmeyer, Norbert; Casabona, Jordi; Castagna, Antonella; Costagliola, Dominique; Dabis, Francois; de Wit, Stéphane; Fätkenheuer, Gerd; Furrer, Hansjakob; Johnson, Anne M.; Lazanas, Marios K.; Leport, Catherine; Moreno, Santiago; Obel, Niels; Post, Frank A.; Reekie, Joanne; Reiss, Peter; Sabin, Caroline; Skaletz-Rorowski, Adriane; Suarez-Lozano, Ignacio; Torti, Carlo; Warszawski, Josiane; Zangerle, Robert; Fabre-Colin, Céline; Kjaer, Jesper; Chene, Genevieve; Grarup, Jesper; Kirk, Ole; Lundgren, Jens; Sabin, Miriam; Johnson, Anne; Lazanas, Mario; Post, Frank; Suarez-Loano, Ignacio; Johnson, Hansjakob Furrer Anne; Touloumi, Giota; Meyer, Laurence; Dabis, François; Krause, Murielle Mary; Ghosn, Jade; de Wolf, Frank; Prins, Maria; Bucher, Heiner; Gibb, Diana; Hamouda, Osamah; Bartmeyer, Barbara; del Amo, Julia

    2013-01-01

    Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV

  7. Late prematurity: a systematic review

    Directory of Open Access Journals (Sweden)

    Luís Carlos Machado Júnior

    2014-06-01

    Full Text Available Objective: this study aimed to review the literature regarding late preterm births (34 weeks to 36 weeks and 6 days of gestation in its several aspects. Sources: the MEDLINE, LILACS, and Cochrane Library databases were searched, and the references of the articles retrieved were also used, with no limit of time. Data synthesis: numerous studies showed a recent increase in late preterm births. In all series, late preterm comprised the majority of preterm births. Studies including millions of births showed a strong association between late preterm birth and neonatal mortality. A higher mortality in childhood and among young adults was also observed. Many studies found an association with several neonatal complications, and also with long-term disorders and sequelae: breastfeeding problems, cerebral palsy, asthma in childhood, poor school performance, schizophrenia, and young adult diabetes. Some authors propose strategies to reduce late preterm birth, or to improve neonatal outcome: use of antenatal corticosteroids, changes in some of the guidelines for early delivery in high-risk pregnancies, and changes in neonatal care for this group. Conclusions: numerous studies show greater mortality and morbidity in late preterm infants compared with term infants, in addition to long-term disorders. More recent studies evaluated strategies to improve the outcomes of these neonates. Further studies on these strategies are needed.

  8. Late effects from hadron therapy

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, Eleanor A.; Chang, Polly Y.

    2004-06-01

    Successful cancer patient survival and local tumor control from hadron radiotherapy warrant a discussion of potential secondary late effects from the radiation. The study of late-appearing clinical effects from particle beams of protons, carbon, or heavier ions is a relatively new field with few data. However, new clinical information is available from pioneer hadron radiotherapy programs in the USA, Japan, Germany and Switzerland. This paper will review available data on late tissue effects from particle radiation exposures, and discuss its importance to the future of hadron therapy. Potential late radiation effects are associated with irradiated normal tissue volumes at risk that in many cases can be reduced with hadron therapy. However, normal tissues present within hadron treatment volumes can demonstrate enhanced responses compared to conventional modes of therapy. Late endpoints of concern include induction of secondary cancers, cataract, fibrosis, neurodegeneration, vascular damage, and immunological, endocrine and hereditary effects. Low-dose tissue effects at tumor margins need further study, and there is need for more acute molecular studies underlying late effects of hadron therapy.

  9. 6. CNS international conference on CANDU maintenance. Proceedings

    International Nuclear Information System (INIS)

    2003-01-01

    The 6th CNS International Conference on CANDU Maintenance took place in Toronto, Ontario on November 16-18, 2003. The theme for the conference was 'Maintenance for Life'. About 270 delegates attended the conference held by the Canadian Nuclear Society. The conference consisted of four parallel sessions, a pattern that continued throughout the conference. Papers were grouped under the following headings: Fuel Channels and End Fittings - Assessments; Fuel Channels and End Fittings - Inspections; Fuel Channels and End Fittings - Maintenance; Fuel Channels and End Fittings - Universal Delivery Machine; Water Upgrading; Performance and Plant Life Improvement; Steam Generator Life Management; Steam Generator Modifications; Steam Generators - Inspections; Steam Generators - Assessments; Maintenance Programs; Feeder Inspections; Feeder Assessment and Mitigation; Valve Maintenance; Instrumentation and Control; Inspection Technology; and Fuel Handling

  10. Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

    Science.gov (United States)

    Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu

    2015-01-01

    Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID:26277384

  11. Gene therapy for CNS diseases – Krabbe disease

    Directory of Open Access Journals (Sweden)

    Mohammad A. Rafi

    2016-06-01

    Full Text Available This is a brief report of the 19th Annual Meeting of the American Society of Gene and Cell Therapy that took place from May 4th through May 7th, 2016 in Washington, DC, USA. While the meeting provided many symposiums, lectures, and scientific sessions this report mainly focuses on one of the sessions on the "Gene Therapy for central nervous system (CNS Diseases" and specifically on the "Gene Therapy for the globoid cell leukodystrophy or Krabbe disease. Two presentations focused on this subject utilizing two animal models of this disease: mice and dog models. Different serotypes of adeno-associate viral vectors (AAV alone or in combination with bone marrow transplantations were used in these research projects. The Meeting of the ASGCT reflected continuous growth in the fields of gene and cell therapy and brighter forecast for efficient treatment options for variety of human diseases.

  12. Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

    Science.gov (United States)

    Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

    2016-01-01

    The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

  13. Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy. Risk-modifying factors

    Energy Technology Data Exchange (ETDEWEB)

    Hille-Betz, Ursula; Soergel, Philipp; Kundu, Sudip; Klapdor, Ruediger; Hillemanns, Peter [Hannover Medical School, Department of Obstetrics and Gynaecology, Hannover (Germany); Vaske, Bernhard [Hannover Medical School, Institute of Medical Biometry and Informatics, Hannover (Germany); Bremer, Michael; Henkenberens, Christoph [Hannover Medical School, Department of Radiation Oncology and Special Oncology, Hannover (Germany)

    2016-01-15

    The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters. (orig.) [German] Ziel dieser Arbeit war es, Parameter zu identifizieren, die Spaetschaeden nach Radiotherapie, ein unguenstiges

  14. Late induced abortion.

    Science.gov (United States)

    Savage, W

    1990-09-01

    In the UK in 1988, 13.3% of abortions were performed at 13 weeks' gestation or later. Reasons for this delay, in addition to the diagnosis through amniocentesis of a fetal abnormality, include late recognition of pregnancy, a change of mind about completing the pregnancy, a failure of primary care physicians to entertain the diagnosis of pregnancy, travel or financial problems, and referral difficulties and scheduling delays. Women with little education and very young women are most likely to present for late abortions. From 13-16 weeks, dilatation and evacuation is the safest method of pregnancy termination. The procedure can be made easier through preparation of the cervix with a prostaglandin pessary or Foley catheter. After 16 weeks, an instillation method is recommended; prostaglandin administration can be intro- or extra-amniotic. Complication rates at 13-19 weeks are 14.5/1000 for vaginal methods of abortion and 7.2/1000 for prostaglandin methods. The risk of complications is 3 times higher for women who have 2nd-trimester abortions through the National Health Service. Although it is not realistic to expect that late abortions ever can be eliminated, improved sex education and contraceptive reliability as well as reforms in the National Health Service could reduce the number substantially. To reduce delay, it is suggested that the National Health Service set up satellite day care units and 1-2 central units in each region to deal quickly with midtrimester abortions. Delays would be further reduced by legislation to allow abortion on request in at least the 1st trimester of pregnancy.

  15. Respective impact of implementation of prevention strategies, colonization with multiresistant bacteria and antimicrobial use on the risk of early- and late-onset VAP: An analysis of the OUTCOMEREA network.

    Directory of Open Access Journals (Sweden)

    Wafa Ibn Saied

    Full Text Available The impact of prevention strategies and risk factors for early-onset (EOP versus late-onset (LOP ventilator-associated pneumonia (VAP are still debated.To evaluate, in a multicenter cohort, the risk factors for EOP and LOP, as the evolution of prevention strategies.7,784 patients with mechanical ventilation (MV for at least 48 hours were selected into the multicenter prospective OUTCOMEREA database (1997-2016. VAP occurring between the 3rd and 6th day of MV defined EOP, while those occurring after defined LOPs. We used a Fine and Gray subdistribution model to take the successful extubation into account as a competing event.Overall, 1,234 included patients developed VAP (EOP: 445 (36%; LOP: 789 (64%. Male gender was a risk factor for both EOP and LOP. Factors specifically associated with EOP were admission for respiratory distress, previous colonization with multidrug-resistant Pseudomonas aeruginosa, chest tube and enteral feeding within the first 2 days of MV. Antimicrobials administrated within the first 2 days of MV were all protective of EOP. ICU admission for COPD exacerbation or pneumonia were early risk factors for LOP, while imidazole and vancomycin use within the first 2 days of MV were protective factors. Late risk factors (between the 3rd and the 6th day of MV were the intra-hospital transport, PAO2-FIO2<200 mmHg, vasopressor use, and known colonization with methicillin-resistant Staphylococcus aureus. Among the antimicrobials administered between the 3rd and the 6th day, fluoroquinolones were the solely protective one.Contrarily to LOP, the risk of EOP decreased across the study time periods, concomitantly with an increase in the compliance with bundle of prevention measures.VAP risk factors are mostly different according to the pneumonia time of onset, which should lead to differentiated prevention strategies.

  16. Is high dose methotrexate without irradiation of the brain sufficiently effective in prevention of CNS disease in children with acute lymphoblastic leukemia?

    International Nuclear Information System (INIS)

    Cap, J.; Foltinova, A.; Kaiserova, E.; Mojzesova, A.; Sejnova, D.; Jamarik, M.

    1998-01-01

    We present 5-year results of treatment in 93 children suffering from acute lymphoblastic leukemia using two therapeutic protocols containing multidrug chemotherapy including high dose methotrexate. We could ascertain different results in standard and high risk patients. In a group of 62 children with standard risk we observed improvement in complete remission rate being 98.9% after induction phase of therapy, only one patient died on septicemia. Relapse rate in this group was 21.2% and that 14. 7% in the bone marrow and 6.5% in CNS and no testicular relapse at all. In the group of 31 children with high risk leukemia all patients achieved complete remission. Only one of them died on acute pancreatitis due to toxicity. Overall relapse rate in this group was 28.9% with 12.8% of medullary relapse and 16.1 % of CNS relapse. The last one was significantly higher than in the previous study when brain irradiation was a part of therapeutic procedure. It seems that this treatment is effective mainly in the standard risk leukemia, however, in the high risk leukemias this procedure appears to be less effective in preventing CNS leukemia. In this group of patients irradiation of the brain need to be enclosed in the therapy. (authors)

  17. IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease

    Directory of Open Access Journals (Sweden)

    Kim Byung S

    2012-09-01

    Full Text Available Abstract Background Theiler’s virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS. IL-1 plays an important role in the pathogenesis of both the autoimmune disease model (EAE and this viral model for MS. However, IL-1 is known to play an important protective role against certain viral infections. Therefore, it is unclear whether IL-1-mediated signaling plays a protective or pathogenic role in the development of TMEV-induced demyelinating disease. Methods Female C57BL/6 mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO were infected with Theiler’s murine encephalomyelitis virus (1 x 106 PFU. Differences in the development of demyelinating disease and changes in the histopathology were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected mice were analyzed using quantitative PCR, ELISA, and flow cytometry. Results Administration of IL-1β, thereby rending resistant B6 mice susceptible to TMEV-induced demyelinating disease, induced a high level of Th17 response. Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6 mice also induced TMEV-induced demyelinating disease. High viral persistence was found in the late stage of viral infection in IL-1R-deficient mice, although there were few differences in the initial anti-viral immune responses and viral persistent levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV-infected IL-1R-deficient mice, leading to deficiencies in T cell function that permit viral persistence. Conclusions These results suggest that the presence of high IL-1 level exerts the pathogenic role by elevating pathogenic Th17 responses, whereas the lack of IL-1 signals promotes viral persistence in the spinal cord due to insufficient T cell activation by elevating the production of

  18. Are we ready to predict late effects?

    DEFF Research Database (Denmark)

    Salz, Talya; Baxi, Shrujal S; Raghunathan, Nirupa

    2015-01-01

    BACKGROUND: After completing treatment for cancer, survivors may experience late effects: consequences of treatment that persist or arise after a latent period. PURPOSE: To identify and describe all models that predict the risk of late effects and could be used in clinical practice. DATA SOURCES:...

  19. Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

    Energy Technology Data Exchange (ETDEWEB)

    Giantsoudi, Drosoula; Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Eaton, Bree R. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Caruso, Paul A.; Rapalino, Otto [Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: smacdonald@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2016-05-01

    Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

  20. Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

    International Nuclear Information System (INIS)

    Giantsoudi, Drosoula; Sethi, Roshan V.; Yeap, Beow Y.; Eaton, Bree R.; Ebb, David H.; Caruso, Paul A.; Rapalino, Otto; Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

    2016-01-01

    Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

  1. Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

    Science.gov (United States)

    Giantsoudi, Drosoula; Sethi, Roshan V; Yeap, Beow Y; Eaton, Bree R; Ebb, David H; Caruso, Paul A; Rapalino, Otto; Chen, Yen-Lin E; Adams, Judith A; Yock, Torunn I; Tarbell, Nancy J; Paganetti, Harald; MacDonald, Shannon M

    2016-05-01

    Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET. Published by Elsevier Inc.

  2. CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

    DEFF Research Database (Denmark)

    Holfort, S K; Lindegaard, J; Isager, P

    2008-01-01

    was observed in two cases (14%). The amount of tumour infiltrating lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had multiple organ metastases, and the average time from the initial CNS symptoms to death...

  3. Risk of Late Mortality and Second Malignant Neoplasms among 5-Year Survivors of Young Adult Cancer: A Report of the Childhood, Adolescent, and Young Adult Cancer Survivors Research Program

    International Nuclear Information System (INIS)

    Zhang, Y.; Spinelli, J. J.; Gotay, C.; McBride, M. L.; Zhang, Y.; Spinelli, J. J.; Goddard, K.

    2012-01-01

    We conducted a population-based retrospective study to assess the long-term risks of overall and cause-specific mortality and second malignant neoplasm (SMN) among survivors of young adult cancer compared to the risk in British Columbia (BC) population and to evaluate the effects of demographic and clinical factors on risk. 1248 5-year survivors of young adult cancer diagnosed 1970-1995 between 20 and 24 years of age were identified from the BC Cancer Registry and followed to the end of 2007. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated. The Cox proportional hazards model was used to estimate the effects of different demographic and disease-related characteristics on the risk of death and SMN. A total of 138 deaths and 62 SMNs were observed during follow-up. The overall SMR was 5.9 (95% CI 4.9-6.9) and the absolute excess risk was 5.3 per 1,000 person-years. The overall SIR was 3.0 (95% CI 2.3-3.8). Treatment with radiation resulted in increased risks of death and SMN. These observed increased risks emphasize the importance of prevention, surveillance, and treatment of late effects in survivors of young adult cancers.

  4. Adverse Life Events and Psychopathology and Prosocial Behavior in Late Adolescence: Testing the Timing, Specificity, Accumulation, Gradient, and Moderation of Contextual Risk

    Science.gov (United States)

    Flouri, Eirini; Kallis, Constantinos

    2007-01-01

    A study examines the role of contextual risk in psychopathology and prosocial behavior in adolescents. The results show that risk accumulation matters instead of specificity and that the number of adverse life events is nonmultiplicative with psychopathology.

  5. HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix

    Science.gov (United States)

    Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki

    2016-01-01

    Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

  6. Therapy of CNS leukemia with intraventricular chemotherapy and low-dose neuraxis radiotherapy

    International Nuclear Information System (INIS)

    Steinherz, P.; Jereb, B.; Galicich, J.

    1985-01-01

    Successful treatment of CNS leukemic relapse has been frustrated by frequent local recurrence and eventual marrow relapse. The authors describe the treatment of meningeal leukemia in 39 children with intrathecal remission induction followed by the placement of an Ommaya reservoir to facilitate the administration and distribution of chemotherapeutic agents into the CSF. Six hundred or 900 rad of craniospinal radiation and maintenance intraventricular and intrathecal chemotherapy was then administered. Systemic reinduction therapy was added in the later cases. Sixteen children (41%) experienced no further events, with 17+ months to 13+ years (median, 25 months) follow-up . Eleven patients (28%) had CNS recurrence, nine (23%) bone marrow (BM) relapse, and two (5%) testicular relapse as the next adverse event. The course of patients with first isolated CNS relapse differed from that of the others. Eleven (69%) of 16 patients treated for first isolated CNS relapse are alive and 9 are event free, while only 35% of patients whose CNS relapse occurred simultaneously or after recurrent disease at other sites are alive (P = .04). Seven of 23 in the later group are event free. The difference is due to the increased incidence of BM relapse in the later group (30% v 6%; P = .04). For patients with first isolated CNS relapse, the life-table median CNS remission duration is 42 months. The projected CNS relapse-free survival and event-free survival 8 to 10 years after CNS relapse are 40% and 32%, respectively. Headache, nausea, and emesis of short duration were frequent during therapy. In three patients, the reservoir had to be removed for infection. No patient suffered neurologic deficit related to the reservoir. The therapy described can reduce the CNS relapse rate with manageable toxicity

  7. CNA/CNS proceedings of the 37. annual conference 1997

    International Nuclear Information System (INIS)

    1997-01-01

    The thirty-seventh meeting of the Canadian Nuclear Association began with a joint session of keynote addresses that included the Canadian Nuclear Society. The other sessions that the 21 papers were organized under have the following titles: international opportunities for the industry, competitiveness in the marketplace, opportunities in the late nineties, moving forward in the late nineties. The conference was concerned mainly with marketing nuclear power plants, especially CANDU plants, but some papers cover such topics as uranium, fusion, and radioisotopes, all from a general, or marketing, aspect. All the individual papers published that come within the scope of INIS have been abstracted separately

  8. CNA/CNS proceedings of the 37. annual conference 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-31

    The thirty-seventh meeting of the Canadian Nuclear Association began with a joint session of keynote addresses that included the Canadian Nuclear Society. The other sessions that the 21 papers were organized under have the following titles: international opportunities for the industry, competitiveness in the marketplace, opportunities in the late nineties, moving forward in the late nineties. The conference was concerned mainly with marketing nuclear power plants, especially CANDU plants, but some papers cover such topics as uranium, fusion, and radioisotopes, all from a general, or marketing, aspect. All the individual papers published that come within the scope of INIS have been abstracted separately.

  9. TIME COURSE MODIFICATIONS INDUCED BY PERINATAL ASPHYXIA IN RAT CNS

    Directory of Open Access Journals (Sweden)

    Francisco Capani

    2015-04-01

    of estradiol treatment we were able to revert some of these alterations using PI3K/Akt/GSK3. Overall these results demonstrate that synaptic dysfunction following PA might be produced by early changes in the actin organization and long-term misfolding and aggregation of proteins in the PSDs. Therefore, we hypothesize that the synaptic and neuronal cytoskeleton changes induced by PA in the rat CNS could lead to the cellular dysfunction and death in adult animals. Estradiol appears as a new therapeutic tool to slacken the damage induces by perinatal asphyxia on the CNS.

  10. Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

    Science.gov (United States)

    Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

    2018-01-01

    Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

  11. Role of galectin-3 in prion infections of the CNS

    International Nuclear Information System (INIS)

    Mok, Simon W.F.; Riemer, Constanze; Madela, Kazimierz; Hsu, Daniel K.; Liu, Fu-Tong; Gueltner, Sandra; Heise, Ines; Baier, Michael

    2007-01-01

    Galectin-3 is a multi-functional protein and participates in mediating inflammatory reactions. The pronounced overexpression of galectin-3 in prion-infected brain tissue prompted us to study the role of this protein in a murine prion model. Immunofluorescence double-labelling identified microglia as the major cell type expressing galectin-3. Ablation of galectin-3 did not affect PrP Sc -deposition and development of gliosis. However, galectin-3 -/- -mice showed prolonged survival times upon intracerebral and peripheral scrapie infections. Moreover, protein levels of the lysosomal activation marker LAMP-2 were markedly reduced in prion-infected galectin-3 -/- -mice suggesting a role of galectin-3 in regulation of lysosomal functions. Lower mRNA levels of Beclin-1 and Atg5 in prion-infected wild-type and galectin-3 -/- -mice indicated an impairment of autophagy although autophagosome formation was unchanged. The results point towards a detrimental role of galectin-3 in prion infections of the CNS and suggest that endo-/lysosomal dysfunction in combination with reduced autophagy may contribute to disease development

  12. Fluids and barriers of the CNS: a historical viewpoint

    Directory of Open Access Journals (Sweden)

    Liddelow Shane A

    2011-01-01

    Full Text Available Abstract Tracing the exact origins of modern science can be a difficult but rewarding pursuit. It is possible for the astute reader to follow the background of any subject through the many important surviving texts from the classical and ancient world. While empirical investigations have been described by many since the time of Aristotle and scientific methods have been employed since the Middle Ages, the beginnings of modern science are generally accepted to have originated during the 'scientific revolution' of the 16th and 17th centuries in Europe. The scientific method is so fundamental to modern science that some philosophers consider earlier investigations as 'pre-science'. Notwithstanding this, the insight that can be gained from the study of the beginnings of a subject can prove important in the understanding of work more recently completed. As this journal undergoes an expansion in focus and nomenclature from cerebrospinal fluid (CSF into all barriers of the central nervous system (CNS, this review traces the history of both the blood-CSF and blood-brain barriers from as early as it was possible to find references, to the time when modern concepts were established at the beginning of the 20th century.

  13. CNS fungal meningitis to the "Top of the basilar"

    Institute of Scientific and Technical Information of China (English)

    Logan CS; Kirschner RC; Simonds GR

    2013-01-01

    Central nervous system(CNS) infections are a rare complication of epidural steroid injections and without strong clinical suspicion, fungal organisms may be overlooked among the long differential of causes of meningitis.Rare sequela of fungal meningitis is the development of stroke.To our knowledge, we present the first case of post epidural steroid injection(ESI) fungal meningitis leading toa basilar artery stroke, otherwise known as“top of the basilar” syndrome.We present a49-year-old female with a history ofESIs who presented to the emergency department with headache, neck stiffness, and abdominal pain.She was discharged after her labs and symptoms were deemed inconsistent with meningitis.She was eventually admitted and twelve days after her originalED visit, she was diagnosed with meningitis and started on anti-fungal treatment.She was discharged88 days later but was readmitted due to left sided weakness and mental status changes.She quickly lost motor and bulbar functions.AnMRA showed diminished distal flow through the basilar artery, suggesting near complete occlusion.Although appropriate long term anti-fungal treatment was started, the patient still succumbed to a rare vascular event.Physicians who are treating patients forESI meningitis should be aware of the potential for vasculitic and encephalitic complications.

  14. Electrophysiological CNS-processes related to associative learning in humans.

    Science.gov (United States)

    Christoffersen, Gert R J; Schachtman, Todd R

    2016-01-01

    The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Stress preconditioning of spreading depression in the locust CNS.

    Directory of Open Access Journals (Sweden)

    Corinne I Rodgers

    Full Text Available Cortical spreading depression (CSD is closely associated with important pathologies including stroke, seizures and migraine. The mechanisms underlying SD in its various forms are still incompletely understood. Here we describe SD-like events in an invertebrate model, the ventilatory central pattern generator (CPG of locusts. Using K(+ -sensitive microelectrodes, we measured extracellular K(+ concentration ([K(+](o in the metathoracic neuropile of the CPG while monitoring CPG output electromyographically from muscle 161 in the second abdominal segment to investigate the role K(+ in failure of neural circuit operation induced by various stressors. Failure of ventilation in response to different stressors (hyperthermia, anoxia, ATP depletion, Na(+/K(+ ATPase impairment, K(+ injection was associated with a disturbance of CNS ion homeostasis that shares the characteristics of CSD and SD-like events in vertebrates. Hyperthermic failure was preconditioned by prior heat shock (3 h, 45 degrees C and induced-thermotolerance was associated with an increase in the rate of clearance of extracellular K(+ that was not linked to changes in ATP levels or total Na(+/K(+ ATPase activity. Our findings suggest that SD-like events in locusts are adaptive to terminate neural network operation and conserve energy during stress and that they can be preconditioned by experience. We propose that they share mechanisms with CSD in mammals suggesting a common evolutionary origin.

  16. Human abuse liability evaluation of CNS stimulant drugs.

    Science.gov (United States)

    Romach, Myroslava K; Schoedel, Kerri A; Sellers, Edward M

    2014-12-01

    Psychoactive drugs that increase alertness, attention and concentration and energy, while also elevating mood, heart rate and blood pressure are referred to as stimulants. Despite some overlapping similarities, stimulants cannot be easily categorized by their chemical structure, mechanism of action, receptor binding profile, effects on monoamine uptake, behavioral pharmacology (e.g., effects on locomotion, temperature, and blood pressure), therapeutic indication or efficacy. Because of their abuse liability, a pre-market assessment of abuse potential is required for drugs that show stimulant properties; this review article focuses on the clinical aspects of this evaluation. This includes clinical trial adverse events, evidence of diversion or tampering, overdoses and the results of a human abuse potential study. While there are different types of human experimental studies that can be employed to evaluate stimulant abuse potential (e.g., drug discrimination, self-administration), only the human abuse potential study and clinical trial adverse event data are required for drug approval. The principal advances that have improved human abuse potential studies include using study enrichment strategies (pharmacologic qualification), larger sample sizes, better selection of endpoints and measurement strategies and more carefully considered interpretation of data. Because of the methodological advances, comparisons of newer studies with historical data is problematic and may contribute to a biased regulatory framework for the evaluation of newer stimulant-like drugs, such as A2 antagonists. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

    OpenAIRE

    de Lange, Elizabeth CM

    2013-01-01

    Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

  18. When the Tail Can't Wag the Dog: The Implications of CNS-Intrinsic Initiation of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Deirdre S Davis

    2009-04-01

    Full Text Available The CNS (central nervous system is unquestionably the central organ that regulates directly or indirectly all physiological systems in the mammalian body. Yet, when considering the defence of the CNS from pathogens, the CNS has often been considered passive and subservient to the pro-inflammatory responses of the immune system. In this view, neuroinflammatory disorders are examples of when the tail (the immune system wags the dog (the CNS to the detriment of an individual's function and survival.

  19. Acute histologic chorioamnionitis is a risk factor for adverse neonatal outcome in late preterm birth after preterm premature rupture of membranes.

    Directory of Open Access Journals (Sweden)

    Seung Mi Lee

    Full Text Available BACKGROUND: The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM. METHODOLOGY/PRINCIPAL FINDINGS: The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005 than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids. CONCLUSIONS/SIGNIFICANCE: The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM.

  20. Acute histologic chorioamnionitis is a risk factor for adverse neonatal outcome in late preterm birth after preterm premature rupture of membranes.

    Science.gov (United States)

    Lee, Seung Mi; Park, Jeong Woo; Kim, Byoung Jae; Park, Chan-Wook; Park, Joong Shin; Jun, Jong Kwan; Yoon, Bo Hyun

    2013-01-01

    The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM. The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids. The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM.

  1. The retina as a window to the brain-from eye research to CNS disorders.

    Science.gov (United States)

    London, Anat; Benhar, Inbal; Schwartz, Michal

    2013-01-01

    Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.

  2. Observations at the CNS-PNS border of ventral roots connected to a neuroma

    Directory of Open Access Journals (Sweden)

    Sten Remahl

    2010-10-01

    Full Text Available Previous studies have shown that numerous sprouts originating from a neuroma, after nerve injury in neonatal animals, can invade spinal nerve roots. In this study the border between the central and peripheral nervous system (CNS-PNS border of ventral roots in kittens was examined with both light and electron microscopy after early postnatal sciatic nerve resection. A transient ingrowth of substance P positive axons was observed into the CNS, but no spouts remained 6 weeks after the injury. Using serial sections and electron microscopy it was possible to identify small bundles of unmyelinated axons that penetrated from the root fascicles for a short distance into the CNS. These axons ended blindly, sometimes with a growth cone-like terminal swelling filled with vesicles. The axon bundles were accompanied by p75 positive cells in both the root fascicles and the pia mater, but not in the CNS. It may thus be suggested that neurotrophin presenting p75 positive cells could facilitate axonal growth into the pia mater and that the lack of such cells in the CNS compartment might contribute to the failure of growth into the CNS. A maldevelopment of myelin sheaths at the CNS-PNS border of motor axons was observed and it seems possible that this could have consequences for the propagation of action potential across this region after neonatal nerve injury.

  3. Late effects of radiation on the central nervous system: role of vascular endothelial damage and glial stem cell survival.

    NARCIS (Netherlands)

    Coderre, J.A.; Morris, G.M.; Micca, P.L.; Hopewell, J.W.; Verhagen, I.; Kleiboer, B.J.; Kogel, A.J. van der

    2006-01-01

    Selective irradiation of the vasculature of the rat spinal cord was used in this study, which was designed specifically to address the question as to whether it is the endothelial cell or the glial progenitor cell that is the target responsible for late white matter necrosis in the CNS. Selective

  4. Feasibility and safety of GliaSite brachytherapy in treatment of CNS tumors following neurosurgical resection

    Directory of Open Access Journals (Sweden)

    Wernicke A

    2010-01-01

    Full Text Available Purpose: To investigate feasibility and safety of GliaSite brachytherapy for treatment of central nervous system (CNS tumors following neurosurgical resection. We report mature results of long-term follow-up, outcomes and toxicity. Materials and Methods: In the period from 2004 to 2007, 10 consecutive adult patients with recurrent, newly diagnosed, and metastatic brain malignancies underwent GliaSite brachytherapy following maximally safe neurosurgical resection. While 6/10 (60% patients were treated for recurrence, having previously been treated with external beam radiotherapy (EBRT, 4/10 (40% received radiotherapy (RT for the first time. A median dose of 52.0 Gy (range, 45.0 - 60.0 Gy was prescribed to 0.5 cm - 1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG criteria were used to assess toxicities associated with this technique. Follow-up was assessed with MRI scans and was available on all enrolled patients. Results: Median follow-up was 38 months (range, 18 - 57 months. Mean size of GliaSite balloon was 3.4 cm (range, 2.0 - 4.0 cm. Median survival was 14.0 months for the entire cohort after the treatment. The 17.6 and 16.0 months average survival for newly diagnosed and recurrent high grade gliomas (HGG, respectively, translated into a three-month improvement in survival in patients with newly diagnosed HGG compared to historical controls (P = 0.033. There were no RTOG grades 3 or 4 acute or late toxicities. Follow-up magnetic resonance imaging (MRI imaging did not identify radiation necrosis. Conclusions: Our data indicate that treatment with GliaSite brachytherapy is feasible, safe and renders acceptable local control, acute and long-term toxicities. We are embarking on testing larger numbers of patients with this treatment modality.

  5. Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

    Directory of Open Access Journals (Sweden)

    Kate Kosmac

    2013-03-01

    Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

  6. Derivation of an occupational exposure limit (OEL) for methylene chloride based on acute CNS effects and relative potency analysis.

    Science.gov (United States)

    Storm, J E; Rozman, K K

    1998-06-01

    The Occupational Safety and Health Administration (OSHA) methylene chloride Permissible Exposure Level (PEL) or 25 ppm is quantitatively derived from mouse tumor results observed in a high-exposure National Toxicology Program bioassay. Because this approach depends on controversial interspecies and low-dose extrapolations, the PEL itself has stimulated heated debate. Here, an alternative safety assessment for methylene chloride is presented. It is based on an acute human lowest-observed-adverse-effect level (LOAEL) of 200 ppm for subtle central nervous system (CNS) depression. Steep, parallel exposure-response curves for anesthetic and subanesthetic CNS effects associated with compounds mechanistically and structurally related to methylene chloride are shown to support a safety factor of two to account for inter-individual variability in response. LOAEL/no-observed-adverse-effect ratios for subtle CNS effects associated with structurally related solvents are shown to support a safety factor range of two to four to account for uncertainty in identifying a subthreshold exposure level. Anesthetic relative potencies and anesthetic/subanesthetic effect level ratios are shown to be constant for the compounds evaluated, demonstrating that subanesthetic relative potencies are also constant. Relative potencies among similarly derived occupational exposure limits (OELs) for solvents structurally related to methylene chloride are therefore used to validate the derived methylene chloride OEL range of 25-50 ppm. Because this safety assessment is based on human (rather than rodent) data and empirical (rather than theoretical) exposure-response relationships and is supported by relative potency analysis, it is a defensible alternative to to the OSHA risk assessment and should positively contribute to the debate regarding the appropriate basis and value for a methylene chloride PEL.

  7. Prediction of the estimated 5-year risk of sudden cardiac death and syncope or non-sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy using late gadolinium enhancement and extracellular volume CMR

    Energy Technology Data Exchange (ETDEWEB)

    Avanesov, Maxim; Weinrich, Julius; Well, Lennart; Tahir, Enver; Adam, Gerhard; Lund, Gunnar [University Hospital Hamburg Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Muench, Julia; Patten, Monica [University Heart Center Hamburg, Department of General and Interventional Cardiology, Hamburg (Germany); DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Luebeck, Hamburg (Germany); Saering, Dennis [University of Applied Sciences, Information Technology and Image Processing, Wedel (Germany); Stehning, Christian [Philips Research, Hamburg (Germany); Bohnen, Sebastian; Radunski, Ulf K.; Muellerleile, Kai [University Heart Center Hamburg, Department of General and Interventional Cardiology, Hamburg (Germany)

    2017-12-15

    To evaluate the ability of late gadolinium enhancement (LGE) and mapping cardiac magnetic resonance (CMR) including native T1 and global extracellular volume (ECV) to identify hypertrophic cardiomyopathy (HCM) patients at risk for sudden cardiac death (SCD) and to predict syncope or non-sustained ventricular tachycardia (VT). A 1.5-T CMR was performed in 73 HCM patients and 16 controls. LGE size was quantified using the 3SD, 5SD and full width at half maximum (FWHM) method. T1 and ECV maps were generated by a 3(3)5 modified Look-Locker inversion recovery sequence. Receiver-operating curve analysis evaluated the best parameter to identify patients with increased SCD risk ≥4% and patients with syncope or non-sustained VT. Global ECV was the best predictor of SCD risk with an area under the curve (AUC) of 0.83. LGE size was significantly inferior to global ECV with an AUC of 0.68, 0.70 and 0.70 (all P < 0.05) for 3SD-, 5SD- and FWHM-LGE, respectively. Combined use of the SCD risk score and global ECV significantly improved the diagnostic accuracy to identify HCM patients with syncope or non-sustained VT. Combined use of the SCD risk score and global ECV has the potential to improve HCM patient selection, benefiting most implantable cardioverter defibrillators. (orig.)

  8. Prediction of the estimated 5-year risk of sudden cardiac death and syncope or non-sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy using late gadolinium enhancement and extracellular volume CMR

    International Nuclear Information System (INIS)

    Avanesov, Maxim; Weinrich, Julius; Well, Lennart; Tahir, Enver; Adam, Gerhard; Lund, Gunnar; Muench, Julia; Patten, Monica; Saering, Dennis; Stehning, Christian; Bohnen, Sebastian; Radunski, Ulf K.; Muellerleile, Kai

    2017-01-01

    To evaluate the ability of late gadolinium enhancement (LGE) and mapping cardiac magnetic resonance (CMR) including native T1 and global extracellular volume (ECV) to identify hypertrophic cardiomyopathy (HCM) patients at risk for sudden cardiac death (SCD) and to predict syncope or non-sustained ventricular tachycardia (VT). A 1.5-T CMR was performed in 73 HCM patients and 16 controls. LGE size was quantified using the 3SD, 5SD and full width at half maximum (FWHM) method. T1 and ECV maps were generated by a 3(3)5 modified Look-Locker inversion recovery sequence. Receiver-operating curve analysis evaluated the best parameter to identify patients with increased SCD risk ≥4% and patients with syncope or non-sustained VT. Global ECV was the best predictor of SCD risk with an area under the curve (AUC) of 0.83. LGE size was significantly inferior to global ECV with an AUC of 0.68, 0.70 and 0.70 (all P < 0.05) for 3SD-, 5SD- and FWHM-LGE, respectively. Combined use of the SCD risk score and global ECV significantly improved the diagnostic accuracy to identify HCM patients with syncope or non-sustained VT. Combined use of the SCD risk score and global ECV has the potential to improve HCM patient selection, benefiting most implantable cardioverter defibrillators. (orig.)

  9. The effect of gender, age, and symptom severity in late-life depression on the risk of all-cause mortality: The Bambuí Cohort Study of Aging

    Science.gov (United States)

    Diniz, Breno S.; Reynolds, Charles F.; Butters, Meryl A.; Dew, Mary Amanda; Firmo, Josélia O. A.; Lima-Costa, Maria Fernanda; Castro-Costa, Erico

    2014-01-01

    Background Increased mortality risk and its moderators is an important, but still under recognized, negative outcome of Late-Life Depression (LLD). Therefore, we aimed to evaluate whether LLD is a risk factor for all-cause mortality in a population-based study with over ten years of follow-up, and addressed the moderating effect of gender and symptom severity on mortality risk. Methods This analysis used data from the Bambuí Cohort Study of Aging. The study population comprised 1.508 (86.5%) of all eligible 1.742 elderly residents. Depressive symptoms were annually evaluated by the GHQ-12, with scores of 5 or higher indicating clinically significant depression. From 1997 to 2007, 441 participants died during 10,648 person-years of follow-up. We estimated the hazard ratio for mortality risk by Cox regression analyses. Results Depressive symptoms were a risk factor for all-cause mortality after adjusting for confounding lifestyle and clinical factors (adjusted HR=1.24 CI95% [1.00–1.55], p=0.05). Mortality risk was significantly elevated in men (adjusted HR=1.45 CI95% [1.01 – 2.07], p=0.04), but not in women (adjusted HR=1.13 CI95% [0.84 – 1.48], p=0.15). We observed a significant interaction between gender and depressive symptoms on mortality risk ((HR= 1.72 CI95% [1.18 – 2.49], p=0.004). Conclusion The present study provides evidence that LLD is a risk factor for all-cause mortality in the elderly, especially in men. The prevention and adequate treatment of LLD may help to reduce premature disability and death among elders with depressive symptoms. PMID:24353128

  10. Exposure to the Holocaust and World War II concentration camps during late adolescence and adulthood is not associated with increased risk for dementia at old age.

    Science.gov (United States)

    Ravona-Springer, Ramit; Beeri, Michal Schnaider; Goldbourt, Uri

    2011-01-01

    Holocaust and Nazi concentration camp survivors were subjects to prolonged and multi-dimensional trauma and stress. The aim of the present study was to assess the association between exposure to such trauma during late adolescence and adulthood with dementia at old age. In 1963, approximately 10,000 male civil servants aged 40-71 participated in the Israel Ischemic Heart Disease (IIHD) study. Of them, 691 reported having survived Nazi concentration camps [concentration Camp Survivors (CCS)]. Additional 2316 participants were holocaust survivors but not concentration camp survivors (HSNCC) and 1688 were born in European countries but not exposed to the Holocaust (NH). Dementia was assessed in 1999-2000, over three decades later, in 1889 survivors of the original IIHD cohort; 139 of whom were CCS, 435 were HSNCC, and 236 were NH. Dementia prevalence was 11.5% in CCS, 12.6% in HSNCC, and 15.7% in NH. The odds ratio of dementia prevalence, estimated by age adjusted logistic regression, for CCS as compared to HSNCC was 0.97 (95% CI: 0.53-1.77), approximate Z = -0.10; p = 0.92. Further adjustment for socioeconomic status, diabetes mellitus, and other co-morbidity at midlife (coronary heart disease, lung, and kidney disease), and height did not change the results substantially. Thus, in subjects who survived until old age, late adolescence and adulthood exposure to extreme stress, as reflected by experiencing holocaust and Nazi concentration camps, was not associated with increased prevalence of dementia. Individuals who survived concentration camps and then lived into old age may carry survival advantages that are associated with protection from dementia and mortality.

  11. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  12. The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Maraldo, M. V.; Jorgensen, M.; Brodin, N. P.

    2014-01-01

    –II classical HL patients 4 x 2 plans for each patient. The lifetime excess risks of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow......IFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique. PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage I...... to the heart, lungs, breasts, and thyroid compared to past,extended fields, even for patients with mediastinal disease. This translated into a significantly reduced estimated risk of cardiovascular disease, secondary cancers, and LYL. CONCLUSIONS: Involved Node Radiotherapy should be considered for pediatric...

  13. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-01-01

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients

  14. CLIPPERS among patients diagnosed with non-specific CNS neuroinflammatory diseases

    DEFF Research Database (Denmark)

    Kerrn-Jespersen, B M; Lindelof, M; Illes, Zsolt

    2014-01-01

    Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is an inflammatory CNS disorder characterized by 1) subacute onset of cerebellar and brainstem symptoms, 2) peripontine contrast-enhancing perivascular lesions with a "salt-and-pepper" appeara...

  15. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

    NARCIS (Netherlands)

    Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T. W.; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; von Bueren, André O.; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

    2016-01-01

    Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally

  16. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

    NARCIS (Netherlands)

    Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; Von Bueren, André O.; Von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; Van Meter, Timothy; Monoranu, Camelia Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; Van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; Von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

    2016-01-01

    Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of

  17. Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

    Directory of Open Access Journals (Sweden)

    Andrea R. Yung

    2018-02-01

    Full Text Available During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR, and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots.

  18. Micropituitarism and cortical dysplasia: an unknown association of two uncommon CNS disorders

    International Nuclear Information System (INIS)

    Blinder, G.; Corat-Simon, J.; Hershkovitz, E.

    2001-01-01

    We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)

  19. Micropituitarism and cortical dysplasia: an unknown association of two uncommon CNS disorders

    Energy Technology Data Exchange (ETDEWEB)

    Blinder, G. [MAR Bikur Cholim Hospital Jerusalem (MOR-MAR), Jerusalem (Israel); Corat-Simon, J. [Dept. of Radiology, Assaf Harofeh Medical Center, Zrifin, Beer Jakov (Israel); Hershkovitz, E. [Dept. of Pediatrics, Soroka Medical Center, Beer Sheba (Israel)

    2001-06-01

    We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)

  20. Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.

    Science.gov (United States)

    Sugai, Keiko; Fukuzawa, Ryuji; Shofuda, Tomoko; Fukusumi, Hayato; Kawabata, Soya; Nishiyama, Yuichiro; Higuchi, Yuichiro; Kawai, Kenji; Isoda, Miho; Kanematsu, Daisuke; Hashimoto-Tamaoki, Tomoko; Kohyama, Jun; Iwanami, Akio; Suemizu, Hiroshi; Ikeda, Eiji; Matsumoto, Morio; Kanemura, Yonehiro; Nakamura, Masaya; Okano, Hideyuki

    2016-09-19

    The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.

  1. Late effects on normal tissues: oesophagus

    International Nuclear Information System (INIS)

    Pavy, J.J.; Bosset, J.F.

    1997-01-01

    Radiation-induced late effects of oesophagus are observed after treatment of various cancers. Acute reactions, mainly oesophagitis, are well known and accurately described; late effects share, for most of these, a common consequence: alteration of the main oesophageal function, namely to conduct the food bolus; clinically they are impaired in terms of mobility and stenosis. More rarely, ulcerations and pseudodiverticulae can be observed. Chemotherapy further increases the risk of late effects, especially in case of concomitant chemo-radiotherapy. All numbers and statistical data on oesophagus late effects should be regarded with caution due to recent changes in the therapeutic attitudes (more and more combined chemotherapy-radiotherapy) and some progress in given cancer locations. A common scale like the LENT-SOMA should enable the clinician to better know these late effects on oesophagus which is required to initiate effective prevention measures and adapted treatments. (authors)

  2. Short Length of Stay After Elective Transfemoral Transcatheter Aortic Valve Replacement is Not Associated With Increased Early or Late Readmission Risk.

    Science.gov (United States)

    Sud, Maneesh; Qui, Feng; Austin, Peter C; Ko, Dennis T; Wood, David; Czarnecki, Andrew; Patel, Vaidehi; Lee, Douglas S; Wijeysundera, Harindra C

    2017-04-24

    Elderly patients undergoing transcatheter aortic valve replacement (TAVR) are at risk of hospital readmission postprocedure. It is not known whether the index hospital length of stay and, specifically, early discharge post-TAVR is associated with an increased risk of readmission. We hypothesized a nonlinear relationship whereby both short and long lengths of stay were associated with increased readmission risk. We performed a retrospective multicenter cohort analysis of patients undergoing elective transfemoral TAVR and surviving to discharge between January 2007 and March 2014. The exposure variable was hospital length of stay measured from the procedure date to the date of discharge and modeled as a continuous variable in a multivariable cause-specific Cox regression. Main outcome measures were 30-day and 1-year all-cause readmissions. The study population consisted of 709 patients with a median length of stay of 6 days (interquartile range, 4-8). At 30-days and 1-year, 13.5% and 44.0% of patients were readmitted, respectively. Although post-TAVR length of stay was not associated with 30-day all-cause readmissions ( P =0.925), there existed a significant association with 1-year readmission ( P =0.010) after adjustment for baseline clinical variables. The association between post-TAVR length of stay and 1-year readmission was linear ( P =0.549 for nonlinearity) with no evidence supporting an increased readmission risk for shorter length of stays. Among elderly survivors of elective transfemoral TAVR, a short postprocedural length of stay was not associated with an increased risk readmission within 30 days or 1 year. However, the risk of 1-year readmission increased with longer post-TAVR lengths of stay. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  3. Changes in the socio-demographic patterning of late adolescent health risk behaviours during the 1990s: analysis of two West of Scotland cohort studies

    Directory of Open Access Journals (Sweden)

    Sweeting Helen

    2011-10-01

    Full Text Available Abstract Background Substance use and sexual risk behaviour affect young people's current and future health and wellbeing in many high-income countries. Our understanding of time-trends in adolescent health-risk behaviour is largely based on routinely collected survey data in school-aged adolescents (aged 15 years or less. Less is known about changes in these behaviours among older adolescents. Methods We compared two cohorts from the same geographical area (West of Scotland, surveyed in 1990 and 2003, to: describe time-trends in measures of smoking, drinking, illicit drug use, early sexual initiation, number of opposite sex sexual partners and experience of pregnancy at age 18-19 years, both overall and stratified by gender and socioeconomic status (SES; and examine the effect of time-trends on the patterning of behaviours by gender and SES. Our analyses adjust for slight between-cohort age differences since age was positively associated with illicit drug use and pregnancy. Results Rates of drinking, illicit drug use, early sexual initiation and experience of greater numbers of sexual partners all increased significantly between 1990 and 2003, especially among females, leading to attenuation and, for early sexual initiation, elimination, of gender differences. Most rates increased to a similar extent regardless of SES. However, rates of current smoking decreased only among those from higher SES groups. In addition, increases in 'cannabis-only' were greater among higher SES groups while use of illicit drugs other than cannabis increased more in lower SES groups. Conclusion Marked increases in female substance use and sexual risk behaviours have implications for the long-term health and wellbeing of young women. More effective preventive measures are needed to reduce risk behaviour uptake throughout adolescence and into early adulthood. Public health strategies should reflect both the widespread prevalence of risk behaviour in young people as

  4. Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

    Science.gov (United States)

    Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

    2013-01-01

    Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

  5. Cerebral infarctions due to CNS infection with Enterobacter sakazakii

    International Nuclear Information System (INIS)

    Gallagher, P.G.; Ball, W.S.

    1991-01-01

    Recent reports have implicated Enterobacter sakazakii, a gram-negative enteric bacillus, in neonatal sepsis and meningitis. Cases of severe central nervous system involvement, including ventriculitis, brain abscess, infarction, and cyst formation, have been described. We present serial head CT findings in a case of neonatal E. sakazakii meningitis complicated by a ring enhancing cerebral infarction which mimicked abscess formation. In meningitis secondary to this agent, a recognized pattern of cerebral hypodensity with or without cystic degeneration late in the course of the infection is likely to represent cerebral infarction rather than an abscess especially if there is a lack of culture evidence of a bacterial infection. (orig.)

  6. Poor Vitamin C Status Late in Pregnancy Is Associated with Increased Risk of Complications in Type 1 Diabetic Women: A Cross-Sectional Study

    DEFF Research Database (Denmark)

    Juhl, Bente; Lauszus, Finn Friis; Lykkesfeldt, Jens

    2017-01-01

    Vitamin C (vitC) is essential for normal pregnancy and fetal development and poor vitC status has been related to complications of pregnancy. We have previously shown lower vitC status in diabetic women throughout pregnancy compared to that of non-diabetic controls. Here, we evaluate...... the relationship between vitC status late in diabetic pregnancy in relation to fetal outcome, complications of pregnancy, diabetic characteristics, and glycemic control based on data of 47 women from the same cohort. We found a significant relationship between the maternal vitC level > or ≤ the 50% percentile...... of 26.6 μmol/L, respectively, and the umbilical cord blood vitC level (mean (SD)): 101.0 μmol/L (16.6) versus 78.5 μmol/L (27.8), p = 0.02; n = 12/16), while no relation to birth weight or Apgar score was observed. Diabetic women with complications of pregnancy had significantly lower vitC levels...

  7. Skin bacterial flora as a potential risk factor predisposing to late bacterial infection after cross-linked hyaluronic acid gel augmentation.

    Science.gov (United States)

    Netsvyetayeva, Irina; Marusza, Wojciech; Olszanski, Romuald; Szyller, Kamila; Krolak-Ulinska, Aneta; Swoboda-Kopec, Ewa; Sierdzinski, Janusz; Szymonski, Zachary; Mlynarczyk, Grazyna

    2018-01-01

    Cross-linked hyaluronic acid (HA) gel is widely used in esthetic medicine. Late bacterial infection (LBI) is a rare, but severe complication after HA augmentation. The aim of this study was to determine whether patients who underwent the HA injection procedure and developed LBI had qualitatively different bacterial flora on the skin compared to patients who underwent the procedure without any complications. The study group comprised 10 previously healthy women with recently diagnosed, untreated LBI after HA augmentation. The control group comprised 17 healthy women who had a similar amount of HA injected with no complications. To assess the difference between the two groups, their skin flora was cultured from nasal swabs, both before and after antibiotic treatment in the study group. A significant increase in the incidence of Staphylococcus epidermidis was detected in the control group ( P =0.000) compared to the study group. The study group showed a significantly higher incidence of Staphylococcus aureus ( P =0.005), Klebsiella pneumoniae ( P =0.006), Klebsiella oxytoca ( P =0.048), and Staphylococcus haemolyticus ( P =0.048) compared to the control group. The bacterial flora on the skin differed in patients with LBI from the control group. The control group's bacterial skin flora was dominated by S. epidermidis . Patients with LBI had a bacterial skin flora dominated by potentially pathogenic bacteria.

  8. Early risk factors for being a bully, victim, or bully/victim in late elementary and early secondary education : The longitudinal TRAILS study

    NARCIS (Netherlands)

    Jansen, D.E.M.C.; Veenstra, R.; Ormel, J.; Verhulst, F.C.; Reijneveld, S.A.

    2011-01-01

    Background: Data regarding the impact of early risk factors on later involvement in bullying are scarce. We investigated the impact of preschool behaviors, family characteristics (socio-economic status, family breakup) and parental mental health on bullying and victimization at age 11 (T1) and age

  9. Early risk factors for being a bully, victim, or bully/victim in late elementary and early secondary education. the longitudinal TRAILS study

    NARCIS (Netherlands)

    D.E.M.C. Jansen (Daniëlle); R. Veenstra (René); J. Ormel (Johan Hans); F.C. Verhulst (Frank); S.A. Reijneveld (Sijmen)

    2011-01-01

    textabstractBackground: Data regarding the impact of early risk factors on later involvement in bullying are scarce. We investigated the impact of preschool behaviors, family characteristics (socio-economic status, family breakup) and parental mental health on bullying and victimization at age 11

  10. IQ in late adolescence/early adulthood, risk factors in middle age, and later cancer mortality in men: the Vietnam Experience Study

    DEFF Research Database (Denmark)

    Batty, G David; Mortensen, Laust Hvas; Gale, Catharine R

    2009-01-01

    (i) examine the relation, if any, of pre-morbid IQ scores at 20 years of age with the risk of later cancer mortality; and (ii) explore the role, if any, of potential mediating factors (e.g. smoking, obesity), assessed in middle age, in explaining the IQ-cancer relation....

  11. [Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

    Science.gov (United States)

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

    Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  12. Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

    Science.gov (United States)

    Mocroft, Amanda; Lundgren, Jens D.; Sabin, Miriam Lewis; Monforte, Antonella d'Arminio; Brockmeyer, Norbert; Casabona, Jordi; Castagna, Antonella; Costagliola, Dominique; Dabis, Francois; De Wit, Stéphane; Fätkenheuer, Gerd; Furrer, Hansjakob; Johnson, Anne M.; Lazanas, Marios K.; Leport, Catherine; Moreno, Santiago; Obel, Niels; Post, Frank A.; Reekie, Joanne; Reiss, Peter; Sabin, Caroline; Skaletz-Rorowski, Adriane; Suarez-Lozano, Ignacio; Torti, Carlo; Warszawski, Josiane; Zangerle, Robert; Fabre-Colin, Céline; Kjaer, Jesper; Chene, Genevieve; Grarup, Jesper; Kirk, Ole

    2013-01-01

    Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP. Please see later in the article for the Editors' Summary PMID:24137103

  13. Personality in Late Midlife

    DEFF Research Database (Denmark)

    Mortensen, Erik Lykke; Flensborg-Madsen, Trine; Molbo, Drude

    2014-01-01

    To analyze associations in late midlife between sex, age, education and social class, and the Big Five personality traits; to analyze associations between personality traits and cognitive ability in late midlife; and to evaluate how these associations are influenced by demographic factors....

  14. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE).

    Science.gov (United States)

    Mocroft, Amanda; Lundgren, Jens D; Sabin, Miriam Lewis; Monforte, Antonella d'Arminio; Brockmeyer, Norbert; Casabona, Jordi; Castagna, Antonella; Costagliola, Dominique; Dabis, Francois; De Wit, Stéphane; Fätkenheuer, Gerd; Furrer, Hansjakob; Johnson, Anne M; Lazanas, Marios K; Leport, Catherine; Moreno, Santiago; Obel, Niels; Post, Frank A; Reekie, Joanne; Reiss, Peter; Sabin, Caroline; Skaletz-Rorowski, Adriane; Suarez-Lozano, Ignacio; Torti, Carlo; Warszawski, Josiane; Zangerle, Robert; Fabre-Colin, Céline; Kjaer, Jesper; Chene, Genevieve; Grarup, Jesper; Kirk, Ole

    2013-01-01

    Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further

  15. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE.

    Directory of Open Access Journals (Sweden)

    Amanda Mocroft

    Full Text Available Few studies have monitored late presentation (LP of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE as HIV diagnosis with a CD4 count <350/mm(3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%. LP was highest in heterosexual males (66.1%, Southern European countries (57.0%, and persons originating from Africa (65.1%. LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97. LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70 and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43.LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and

  16. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

    Science.gov (United States)

    Eckert, C; Hagedorn, N; Sramkova, L; Mann, G; Panzer-Grümayer, R; Peters, C; Bourquin, J-P; Klingebiel, T; Borkhardt, A; Cario, G; Alten, J; Escherich, G; Astrahantseff, K; Seeger, K; Henze, G; von Stackelberg, A

    2015-08-01

    The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD treatment reduced MRD to treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs.

  17. Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Kristel Kegler

    Full Text Available Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas

  18. Early risk factors for being a bully, victim, or bully/victim in late elementary and early secondary education. The longitudinal TRAILS study

    Directory of Open Access Journals (Sweden)

    Ormel Johan

    2011-06-01

    Full Text Available Abstract Background Data regarding the impact of early risk factors on later involvement in bullying are scarce. We investigated the impact of preschool behaviors, family characteristics (socio-economic status, family breakup and parental mental health on bullying and victimization at age 11 (T1 and age 13.5 (T2. Methods longitudinal data from a subsample of the TRacking Adolescents' Individual Lives Survey (TRAILS (T1: N = 982; T2: N = 977. TRAILS is a prospective study of adolescent mental health in a mixed urban and rural region of the Netherlands. At T1 parents reported on family characteristics, parental mental health and retrospectively on children's preschool behavior at age 4-5. Schoolmates reported involvement of adolescents in bullying or victimization at T1 and T2. Results Children with preschool anxiety were less likely to be bully/victim at T1. Children with preschool aggressiveness were more likely to be bully (T1, bully/victim (T1 and T2 and victim (T2 and children with good preschool motor functioning were more likely to be bully (T1 and less likely to be victim (T1 and T2. Children from low socioeconomic status families were more likely be to be bully, victim, or bully/victim and less likely to be uninvolved both at T1 and T2. Finally, children from intact two parent families were more likely to be uninvolved at T2. Conclusion Preschool behavioral, emotional and motor problems, socioeconomic status, and family breakup are related to involvement in bullying at a later age. Prevention of bullying and its consequences can be enhanced by focusing on risk groups in early life.

  19. Risk and vulnerability to ENSO flooding in the Peruvian Atacama Desert: paleofloods, floodplain development, and agrarian strategies during the late Holocene

    Science.gov (United States)

    Magilligan, F. J.; Goldstien, P.

    2011-12-01

    River restoration projects with the goal of restoring a wide range of morphologic and ecologic channel processes and functions have become common. The complex interactions between flow and sediment-transport make it challenging to design river channels that are both self-sustaining and improve ecosystem function. The relative immaturity of the field of river restoration and shortcomings in existing methodologies for evaluating channel designs contribute to this problem, often leading to project failures. The call for increased monitoring of constructed channels to evaluate which restoration techniques do and do not work is ubiquitous and may lead to improved channel restoration projects. However, an alternative approach is to detect project flaws before the channels are built by using numerical models to simulate hydraulic and sediment-transport processes and habitat in the proposed channel (Restoration Design Analysis). Multi-dimensional models provide spatially distributed quantities throughout the project domain that may be used to quantitatively evaluate restoration designs for such important metrics as (1) the change in water-surface elevation which can affect the extent and duration of floodplain reconnection, (2) sediment-transport and morphologic change which can affect the channel stability and long-term maintenance of the design; and (3) habitat changes. These models also provide an efficient way to evaluate such quantities over a range of appropriate discharges including low-probability events which often prove the greatest risk to the long-term stability of restored channels. Currently there are many free and open-source modeling frameworks available for such analysis including iRIC, Delft3D, and TELEMAC. In this presentation we give examples of Restoration Design Analysis for each of the metrics above from projects on the Russian River, CA and the Kootenai River, ID. These examples demonstrate how detailed Restoration Design Analysis can be used to

  20. CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

    Science.gov (United States)

    Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

    2009-12-01

    While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

  1. Current approaches to enhance CNS delivery of drugs across the brain barriers

    Directory of Open Access Journals (Sweden)

    Lu CT

    2014-05-01

    Full Text Available Cui-Tao Lu,1 Ying-Zheng Zhao,2,3 Ho Lun Wong,4 Jun Cai,5 Lei Peng,2 Xin-Qiao Tian1 1The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Hainan Medical College, Haikou City, Hainan Province, People’s Republic of China; 3College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, People’s Republic of China; 4School of Pharmacy, Temple University, Philadelphia, PA, USA; 5Departments of Pediatrics and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine Louisville, KY, USA Abstract: Although many agents have therapeutic potentials for central nervous system (CNS diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB, central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF

  2. Foxp3+ regulatory T cells control persistence of viral CNS infection.

    Directory of Open Access Journals (Sweden)

    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  3. Detail Design of the hydrogen system and the gas blanketing system for the HANARO-CNS

    International Nuclear Information System (INIS)

    Choi, Jung Woon; Kim, Hark Rho; Kim, Young Ki; Wu, Sang Ik; Kim, Bong Su; Lee, Yong Seop

    2007-04-01

    The cold neutron source (CNS), which will be installed in the vertical CN hole of the reflector tank at HANARO, makes thermal neutrons to moderate into the cold neutrons with the ranges of 0.1 ∼ 10 meV passing through a moderator at about 22K. A moderator to produce cold neutrons is liquid hydrogen, which liquefies by the heat transfer with cryogenic helium flowing from the helium refrigeration system (HRS). Because of its installed location, the hydrogen system is designed to be surrounded by the gas blanketing system to notify the leakage on the system and to prevent hydrogen leakage out of the CNS. The hydrogen system, consisted of hydrogen charging unit, hydrogen storage unit, hydrogen buffer tank, and hydrogen piping, is designed to smoothly and safely supply hydrogen to and to draw back hydrogen from the IPA of the CNS under the HRS operation mode. Described is that calculation for total required hydrogen amount in the CNS as well as operation schemes of the hydrogen system. The gas blanketing system (GBS) is designed for the supply of the compressed nitrogen gas into the air pressurized valves for the CNS, to isolate the hydrogen system from the air and the water, and to prevent air or water intrusion into the vacuum system as well as the hydrogen system. All detail descriptions are shown inhere as well as the operation scheme for the GBS

  4. CNS metabolism in high-risk drug abuse, German version. Insights gained from {sup 1}H- and {sup 31}P MRS and PET; ZNS-Stoffwechsel bei Missbrauch von Hochrisikodrogen. Erkenntnisse durch {sup 1}H- und {sup 31}P-MRS sowie PET

    Energy Technology Data Exchange (ETDEWEB)

    Bodea, S.V. [Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany)

    2017-06-15

    High-risk drug consumption is a considerable problem for public health actors in industrialised countries. The latest trends show a market tendency towards diversification and increasing demand for high-purity synthetic drugs. Whilst most consumers seek medical help after cannabis use, it is high-risk drugs like cocaine, heroin and amphetamines that account for most of the 1000 drug-related deaths that occur in Germany every year. This article presents the most prominent in vivo cerebral metabolic information in cocaine, heroin and methamphetamine users provided by MRI spectroscopy and PET imaging. We reviewed the literature reporting neuroimaging studies of in vivo metabolic data for methamphetamine, cocaine and heroin consumption published up to March 2017. The search was conducted using PubMed with the following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET. MRI and PET are indispensable tools in gauging brain metabolic response to illegal drug abuse. Future breakthroughs in this field will most likely come from the investigation of novel neurotransmitter systems in PET and imaging phosphorus and carbon metabolites in MRI. (orig.) [German] In den Industrielaendern ist der Konsum von Hochrisikodrogen ein erhebliches Problem fuer das gesamte Gesundheitssystem. Neueste Entwicklungen zeigen eine Tendenz zu immer groesserer Diversifikation und eine erhoehte Nachfrage nach synthetischen Drogen von hohem Reinheitsgrad. Waehrend die meisten Konsumenten medizinische Hilfe nach Cannabisverbrauch suchen, sind es die Hochrisikodrogen wie Heroin, Kokain und Amphetamine, an denen die meisten der 1000 Drogentoten pro Jahr in Deutschland sterben. In diesem Artikel werden die auffaelligsten, mithilfe der Magnetresonanzspektroskopie (MRS) und Positronenemissionstomographie (PET) erfassten In-vivo-Daten zum Hirnstoffwechsel bei Konsumenten von Kokain, Heroin und Methamphetaminen vorgestellt. Die Literatur ueber den zerebralen Energiestoffwechsel bei

  5. Late-Stage Caregiving

    Science.gov (United States)

    ... Caregiving Middle-Stage Caregiving Late-Stage Caregiving Behaviors Aggression & Anger Anxiety & Agitation Depression Hallucinations Memory Loss & Confusion Repetition Sleep Issues & Sundowning Suspicion & Delusions Wandering Abuse Start Here What You Need to Know Online ...

  6. Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus.

    Science.gov (United States)

    Das, Trina; Jaffar-Bandjee, Marie Christine; Hoarau, Jean Jacques; Krejbich Trotot, Pascale; Denizot, Melanie; Lee-Pat-Yuen, Ghislaine; Sahoo, Renubala; Guiraud, Pascale; Ramful, Duksha; Robin, Stephanie; Alessandri, Jean Luc; Gauzere, Bernard Alex; Gasque, Philippe

    2010-06-01

    Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an acute symptomatic illness with fever, skin rash, and incapacitating arthralgia, which can evolve into chronic rheumatoid arthritis in elderly patients. This is a tropical disease originally described in central/east Africa in the 1960s, but its 2004 re-emergence in Africa and rapid spread in lands in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to almost 6 million cases worldwide. The risk of importation and spreading diseases with long-term sequelae is even greater today given the global distribution of the vectors (including in the Americas), increased tourism and the apparent capacity of CHIKV to produce high levels of viremia (10(9)-10(12) virus/ml of blood) and new mutants. CHIKV-associated neuropathology was described early in the 1960s, but it is the unprecedented incidence rate in Indian Ocean areas with efficient clinical facilities that allowed a better description of cases with severe encephalitis, meningoencephalitis, peripheral neuropathies and deaths among newborns (mother-to-child infection), infants and elderly patients. Death rates following CHIKV infection were estimated at 1:1000 cases in la Reunion's outbreak. These clinical observations have been corroborated by experimental infection in several mouse models, leading to CNS pathologies. We further describe in this review the capacity of CHIKV to infect neurons and glial cells, delineate the fundamental innate (intrinsic) immune defence mechanisms to protect from infection and argue about the possible mechanisms involved in the encephalopathy. (c) 2010 Elsevier Ltd. All rights reserved.

  7. [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

    DEFF Research Database (Denmark)

    Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

    2014-01-01

    -azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

  8. Serial brain MRI findings in CNS involvement of familial erythrophagocytic lymphohistiocytosis: a case report

    International Nuclear Information System (INIS)

    Cho, Kyung Soo; Yoo, Jeong Hyun; Suh, Jeong Soo; Ryu, Kyung Ha; Hong, Ki Sook; Kim, Hak Jin

    2002-01-01

    Familial erythrophagocytic lymphohistiocytosis is a fatal early childhood disorder characterized by multiorgan lymphohistiocytic infiltration and active hemophagocytosis. Involvement of the central nervous system (CNS) is not uncommon and is characterized by rapidly progressive tissue damage affecting both the gray and white matter. We encountered a case of familial erythrophagocytic lymphohistiocytosis with CNS involvement. Initial T2-weighted MRI of the brain demonstrated high signal intensity in the right thalamus, though after chemotherapy, which led to the relief of neurologic symptoms, this disappeared. After four months. however, the patient's neurologic symptoms recurred, and follow-up T2-weighted MR images showed high signal intensity in the thalami, basal ganglia, and cerebral and cerebellar white matter. Brain MRI is a useful imaging modality for the evaluation of CNS involvement and monitoring the response to treatment

  9. Analysis of neurocognitive function and CNS endpoints in the PROTEA trial

    DEFF Research Database (Denmark)

    Clarke, Amanda; Johanssen, Veronika; Gerstoft, Jan

    2014-01-01

    INTRODUCTION: During treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF) is lower, compared to standard triple therapy. However, the clinical consequences are unclear. METHODS: A total of 273 patients with HIV...... and the Grooved Pegboard Test at screening, baseline and at Week 48. A global neurocognitive score (NPZ-5) was derived by averaging the standardized results of the five domains. In a central nervous system (CNS) sub-study (n=70), HIV RNA levels in the CNS were evaluated at baseline and Week 48. Clinical adverse...... events related to the CNS were collected at each visit. RESULTS: Patients were 83% male and 88% White, with median age 43 years. There were more patients with nadir CD4 count below 200 cells/µL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm (30/136, 22%). At Week 48...

  10. Intellectual abilities among survivors of childhood leukaemia as a function of CNS irradiation

    International Nuclear Information System (INIS)

    Eiser, C.

    1978-01-01

    Twenty-eight children in remission at least 2 years after completing chemotherapy for acute lymphoblastic leukaemia were assessed on standardised psychological tests. It was found that 7 who never had central nervous system (CNS) irradiation and 9 having prophylactic CNS irradiation at least 6 months after diagnosis tended to perform at average or above levels, while those 10 each having prophylactic CNS irradiation (within 2 months of diagnosis) were generally at lower ability. Within the latter group 3 children showed serious intellectual impairments, while the group as a whole functioned especially poorly on quantitative tasks and those involving speeded performance with abstract material. General language ability was not affected. Practical and theoretical implications are discussed. (author)

  11. Neonatal CNS infection and inflammation caused by Ureaplasma species: rare or relevant?

    Science.gov (United States)

    Glaser, Kirsten; Speer, Christian P

    2015-02-01

    Colonization with Ureaplasma species has been associated with adverse pregnancy outcome, and perinatal transmission has been implicated in the development of bronchopulmonary dysplasia in preterm neonates. Little is known about Ureaplasma-mediated infection and inflammation of the CNS in neonates. Controversy remains concerning its incidence and implication in the pathogenesis of neonatal brain injury. In vivo and in vitro data are limited. Despite improving care options for extremely immature preterm infants, relevant complications remain. Systematic knowledge of ureaplasmal infection may be of great benefit. This review aims to summarize pathogenic mechanisms, clinical data and diagnostic pitfalls. Studies in preterm and term neonates are critically discussed with regard to their limitations. Clinical questions concerning therapy or prophylaxis are posed. We conclude that ureaplasmas may be true pathogens, especially in preterm neonates, and may cause CNS inflammation in a complex interplay of host susceptibility, serovar pathogenicity and gestational age-dependent CNS vulnerability.

  12. Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification

    Directory of Open Access Journals (Sweden)

    McGavern Dorian B

    2007-06-01

    Full Text Available Abstract Once a virus infection establishes persistence in the central nervous system (CNS, it is especially difficult to eliminate from this specialized compartment. Therefore, it is of the utmost importance to fully understand scenarios during which a persisting virus is ultimately purged from the CNS by the adaptive immune system. Such a scenario can be found following infection of adult mice with an immunosuppressive variant of lymphocytic choriomeningitis virus (LCMV referred to as clone 13. In this study we demonstrate that following intravenous inoculation, clone 13 rapidly infected peripheral tissues within one week, but more slowly inundated the entire brain parenchyma over the course of a month. During the establishment of persistence, we observed that genetically tagged LCMV-specific cytotoxic T lymphocytes (CTL progressively lost function; however, the severity of this loss in the CNS was never as substantial as that observed in the periphery. One of the most impressive features of this model system is that the peripheral T cell response eventually regains functionality at ~60–80 days post-infection, and this was associated with a rapid decline in virus from the periphery. Coincident with this "reanimation phase" was a massive influx of CD4 T and B cells into the CNS and a dramatic reduction in viral distribution. In fact, olfactory bulb neurons served as the last refuge for the persisting virus, which was ultimately purged from the CNS within 200 days post-infection. These data indicate that a functionally revived immune response can prevail over a virus that establishes widespread presence both in the periphery and brain parenchyma, and that therapeutic enhancement of an existing response could serve as an effective means to thwart long term CNS persistence.

  13. CD11c-expressing cells affect Treg behavior in the meninges during CNS infection1

    Science.gov (United States)

    O’Brien, Carleigh A.; Overall, Christopher; Konradt, Christoph; O’Hara Hall, Aisling C.; Hayes, Nikolas W.; Wagage, Sagie; John, Beena; Christian, David A.; Hunter, Christopher A.; Harris, Tajie H.

    2017-01-01

    Treg cells play an important role in the CNS during multiple infections as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, the Treg cells in the CNS during T. gondii infection are Th1-polarized, exemplified by T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4+ T cells, an MHC Class II tetramer reagent specific for T. gondii did not recognize Treg cells isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector and regulatory T cells in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Treg cells were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+ T cells within the meninges were highly migratory, while Treg cells moved more slowly and were found in close association with CD11c+ cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+ cells, mice were treated with anti-LFA-1 antibodies to reduce the number of CD11c+ cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+ cells and increased the speed of Treg cell migration. These data suggest that Treg cells are anatomically restricted within the CNS and the interaction with CD11c+ populations regulates their local behavior during T. gondii infection. PMID:28389591

  14. Kinetic modelling of [123I]CNS 1261--a potential SPET tracer for the NMDA receptor

    International Nuclear Information System (INIS)

    Erlandsson, Kjell; Bressan, Rodrigo A.; Mulligan, Rachel S.; Gunn, Roger N; Cunningham, Vincent J.; Owens, Jonathan; Wyper, David; Ell, Peter J.; Pilowsky, Lyn S.

    2003-01-01

    N-(1-napthyl)-N'-(3-[ 123 I]-iodophenyl)-N-methylguanidine ([ 123 I]CNS 1261) is a novel SPET ligand developed for imaging the NMDA receptor intra-channel MK 801/PCP/ketamine site. Data was acquired in 7 healthy volunteers after bolus injection of [ 123 I]CNS 1261. Kinetic modeling showed reversible tracer binding. Arterial and venous time-activity curves overlapped after 90 min. The rank order of binding was: Thalamus > striatum > cortical regions > white matter. This distribution concurs with [ 11 C]-ketamine and [ 18 F]-memantine PET studies . These data provide a methodological basis for further direct in vivo challenge studies

  15. Lentiviral-mediated administration of IL-25 in the CNS induces alternative activation of microglia

    DEFF Research Database (Denmark)

    Maiorino, C; Khorooshi, R; Ruffini, F

    2013-01-01

    Interleukin-25 (IL-25) is the only anti-inflammatory cytokine of the IL-17 family, and it has been shown to be efficacious in inhibiting neuroinflammation. Known for its effects on cells of the adaptive immune system, it has been more recently described to be effective also on cells of the innate...... was partly inhibited and the CNS protected from immune-mediated damage. To our knowledge, this is the first example of M2 shift (alternative activation) induced in vivo on CNS-resident myeloid cells by gene therapy, and may constitute a promising strategy to investigate the potential role of protective...

  16. Metallothionein-1+2 protect the CNS after a focal brain injury

    DEFF Research Database (Denmark)

    Giralt, Mercedes; Penkowa, Milena; Lago, Natalia

    2002-01-01

    We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number...... dramatically reduced the cryolesion-induced oxidative stress and neuronal apoptosis. Remarkably, these effects were also obtained by the intraperitoneal administration of MT-2 to both normal and MT-1+2 knock-out mice. These results fully support the notion that MT-1+2 are essential in the CNS for coping...

  17. Imaging aspects of neurologic emergencies in children treated for non-CNS malignancies

    International Nuclear Information System (INIS)

    Kaste, S.C.; Langston, J.; Rodriguez-Galindo, C.; Furman, W.L.; Thompson, S.J.

    2000-01-01

    There is a paucity of radiologic literature addressing neurologic emergencies in children receiving therapy for non-CNS primary malignancies. In the acute setting, many of these children present to local community hospitals. This pictorial is from a single institutional experience describing the spectrum of neurologic emergencies seen in children with non-CNS cancers. We hope to familiarize pediatric radiologists with these entities in order to expedite diagnosis, facilitate treatment, and minimize morbity and mortality that may be associated with these complications. (orig.)

  18. Neuroprotective effects of estrogen in CNS injuries: insights from animal models

    Directory of Open Access Journals (Sweden)

    Raghava N

    2017-07-01

    Full Text Available Narayan Raghava,1 Bhaskar C Das,2 Swapan K Ray1 1Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2 is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS injuries such as spinal cord injury (SCI, traumatic brain injury (TBI, and ischemic brain injury (IBI. These CNS injuries are not only serious health problems, but also enormous economic burden on the patients, their families, and the society at large. Studies from animal models of these CNS injuries provide insights into the multiple neuroprotective mechanisms of E2 and also suggest the possibility of translating the therapeutic efficacy of E2 in the treatment SCI, TBI, and IBI in humans in the near future. The pathophysiology of these injuries includes loss of motor function in the limbs, arms and their extremities, cognitive deficit, and many other serious consequences including life-threatening paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal models. Because activation of estrogen receptors has profound implications in maintaining and also affecting normal physiology, there are notable impediments in translating E2 therapy to the clinics for neuroprotection in CNS injuries in humans. While E2 may not yet be the sole molecule for

  19. Causes for Late onset Alcohol Use Disorder

    DEFF Research Database (Denmark)

    Emiliussen, Jakob; Nielsen, Anette Søgaard; Andersen, Kjeld

    the studies. The results of this review are generally inconclusive. In spite of the low quality scores, we did find that chronic stress, role/identity loss and friends approval of drinking, was associated with an increased risk for late-onset AUD whereas retirement, death of spouse or close relative does...

  20. [Late primary abdominal pregnancy. Case report].

    Science.gov (United States)

    Farías, Emigdio Torres; Gómez, Luis Guillermo Torres; Allegre, René Márquez; Higareda, Salvador Hernández

    2008-09-01

    Abdominal advanced pregnancy is an obstetric complication that put at risk maternal and fetal life. We report a case of advanced abdominal pregnancy with intact ovaries and fallopian tubes, without ureteroperitoneal fistulae and, late prenatal diagnosis, in a multiparous patient without risk factors, with alive newborn, and whose pregnancy was attended at Unidad Medica de Alta Especialidad, Hospital de Gineco-Obstetricia, Centro Medico Nacional de Occidente del IMSS, Guadalajara, Jalisco, México.

  1. Late onset endophthalmitis

    Directory of Open Access Journals (Sweden)

    Abdulaziz AlHadlaq

    2016-04-01

    Full Text Available We report an extremely rare presentation of late-onset endophthalmitis in a young adult patient with an unexposed Ahmed tube implant. The implant was inserted 11 years prior to presentation. There was no history of trauma or any obvious exposure on clinical examination and the tube plate was filled with purulent material. After aqueous and vitreous tap, the patient underwent intracameral, intravitreal subconjunctival antibiotic injections and was started on systemic antibiotics with good response. Endophthalmitis associated with tube drainage device can present as late as 11 years and even without an unexposed tube.

  2. Intraoperative squash smear cytology in CNS lesions: A study of 150 pediatric cases

    Directory of Open Access Journals (Sweden)

    Arpita Jindal

    2017-01-01

    Full Text Available Background: Tumors of the central nervous system in the pediatric age group occur relatively frequently during the early years of life. Brain tumors are the most common solid malignancies of childhood and only second to acute childhood leukemia. Squash cytology is an indispensable diagnostic aid to central nervous system (CNS lesions. The definitive diagnosis of brain lesions is confirmed by histological examination. Aim: To study the cytology of CNS lesions in pediatric population and correlate it with histopathology. Materials and Methods: One hundred and fifty cases of CNS lesions in pediatric patients were studied over a period of 2 years. Intraoperative squash smears were prepared, stained with hematoxylin and eosin, and examined. Remaining sample was subjected to histopathological examination. Results: Medulloblastoma (24.0% was the most frequently encountered tumor followed by pilocyctic astrocytoma (21.33% and ependymoma (13.33%. Diagnostic accuracy of squash smear technique was 94.67% when compared with histological diagnosis. Conclusion: Smear cytology is a fairly accurate tool for intraoperative CNS consultations.

  3. Mining the topography and dynamics of the 4D Nucleome to identify novel CNS drug pathways.

    Science.gov (United States)

    Higgins, Gerald A; Allyn-Feuer, Ari; Georgoff, Patrick; Nikolian, Vahagn; Alam, Hasan B; Athey, Brian D

    2017-07-01

    The pharmacoepigenome can be defined as the active, noncoding province of the genome including canonical spatial and temporal regulatory mechanisms of gene regulation that respond to xenobiotic stimuli. Many psychotropic drugs that have been in clinical use for decades have ill-defined mechanisms of action that are beginning to be resolved as we understand the transcriptional hierarchy and dynamics of the nucleus. In this review, we describe spatial, temporal and biomechanical mechanisms mediated by psychotropic medications. Focus is placed on a bioinformatics pipeline that can be used both for detection of pharmacoepigenomic variants that discretize drug response and adverse events to improve pharmacogenomic testing, and for the discovery of novel CNS therapeutics. This approach integrates the functional topology and dynamics of the transcriptional hierarchy of the pharmacoepigenome, gene variant-driven identification of pharmacogenomic regulatory domains, and mesoscale mapping for the discovery of novel CNS pharmacodynamic pathways in human brain. Examples of the application of this pipeline are provided, including the discovery of valproic acid (VPA) mediated transcriptional reprogramming of neuronal cell fate following injury, and mapping of a CNS pathway glutamatergic pathway for the mood stabilizer lithium. These examples in regulatory pharmacoepigenomics illustrate how ongoing research using the 4D nucleome provides a foundation to further insight into previously unrecognized psychotropic drug pharmacodynamic pathways in the human CNS. Copyright © 2017. Published by Elsevier Inc.

  4. Inflammatory cytokines in the brain: does the CNS shape immune responses?

    DEFF Research Database (Denmark)

    Owens, T; Renno, T; Taupin, V

    1994-01-01

    Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far ...

  5. A safety assessment methodology applied to CNS/ATM-based air traffic control system

    Energy Technology Data Exchange (ETDEWEB)

    Vismari, Lucio Flavio, E-mail: lucio.vismari@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil); Batista Camargo Junior, Joao, E-mail: joaocamargo@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil)

    2011-07-15

    In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

  6. Durable treatment response of relapsing CNS plasmacytoma using intrathecal chemotherapy, radiotherapy, and Daratumumab.

    Science.gov (United States)

    Elhassadi, Ezzat; Murphy, Maurice; Hacking, Dayle; Farrell, Michael

    2018-04-01

    CNS myelomatous involvement is a rare complication of multiple myeloma with dismal outcome. This disease's optimal treatment is unclear. Combined approach of systemic therapy, radiotherapy, and intrathecal injections chemotherapy should be considered and autologous stem cell transplant consolidation is offered to eligible patients. The role of Daratumumab in this disease deserves further evaluation.

  7. Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers

    Directory of Open Access Journals (Sweden)

    Jessica L Williams

    2014-05-01

    Full Text Available In the adult central nervous system (CNS, chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

  8. Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi.

    Science.gov (United States)

    Malik, Jai; Karan, Maninder; Vasisht, Karan

    2011-12-01

    Shankhpushpi, a well-known drug in Ayurveda, is extensively used for different central nervous system (CNS) effects especially memory enhancement. Different plants are used under the name shankhpushpi in different regions of India, leading to an uncertainty regarding its true source. Plants commonly used under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn. (Leguminosae). To find out the true source of shankhpushpi by evaluating and comparing memory-enhancing activity of the three above mentioned plants. Anxiolytic, antidepressant and CNS-depressant activities of these three plants were also compared and evaluated. The nootropic activity of the aqueous methanol extract of each plant was tested using elevated plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS-depressant studies were evaluated using EPM, Porsolt?s swim despair and actophotometer models, respectively. C. pluricaulis extract (CPE) at a dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p nootropic, anxiolytic and CNS-depressant activity. The results of memory-enhancing activity suggest C. pluricaulis to be used as true source of shankhpushpi.

  9. Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease.

    Science.gov (United States)

    Brown, Melissa A; Weinberg, Rebecca B

    2018-01-01

    Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.

  10. Immune cell entry to the CNS--a focus for immunoregulation of EAE

    DEFF Research Database (Denmark)

    Owens, T; Tran, E; Hassan-Zahraee, M

    1999-01-01

    -requirement then to prove such a role. The point that emerges is that cytokine production in the CNS parenchyma is itself dependent on the prior infiltration of immune cells, and that without immune cell entry, EAE does not occur. This identifies events at the BBB, and in particular in the perivascular space, as critical...

  11. Migration, fate and in vivo imaging of stem cells in the CNS

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva

    2009-01-01

    Roč. 16, Suppl.3 (2009), s. 4-4 ISSN 1351-5101. [Congress of the European-Federation-of-Neurological-Societies /13./. 12.09.2009-15.09.2009, Florencie] Institutional research plan: CEZ:AV0Z50390703 Keywords : CNS * ESC Subject RIV: FH - Neurology

  12. Comparative analysis of acid sphingomyelinase distribution in the CNS of rats and mice following intracerebroventricular delivery.

    Directory of Open Access Journals (Sweden)

    Christopher M Treleaven

    Full Text Available Niemann-Pick A (NPA disease is a lysosomal storage disorder (LSD caused by a deficiency in acid sphingomyelinase (ASM activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO mice could be partially alleviated by intracerebroventricular (ICV infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat.

  13. CNS Damage Classification in Newborn Infants by Neural Network Based Cry Analysis

    NARCIS (Netherlands)

    Poel, Mannes; Ekkel, T.

    2002-01-01

    The central nervous system (CNS) of the human body is the whole system of brain, spinal marrow and nerve cells throughout the body that correlates and regulates the internal reactions of the body and controls its adjustment to the environment. It controls muscles and processes sensory information

  14. CSF Hypocretin-1 Levels and Clinical Profiles in Narcolepsy and Idiopathic CNS Hypersomnia in Norway

    Science.gov (United States)

    Heier, Mona Skard; Evsiukova, Tatiana; Vilming, Steinar; Gjerstad, Michaela D.; Schrader, Harald; Gautvik, Kaare

    2007-01-01

    Objective: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. Method: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. Results: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. Conclusion: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings. Citation: Heier MS; Evsiukova T; Vilming S; Gjerstad MD; Schrader H; Gautvik K. CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in norway. SLEEP 2007;30(8):969-973. PMID:17702265

  15. A safety assessment methodology applied to CNS/ATM-based air traffic control system

    International Nuclear Information System (INIS)

    Vismari, Lucio Flavio; Batista Camargo Junior, Joao

    2011-01-01

    In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

  16. Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent patients with primary CNS lymphoma

    International Nuclear Information System (INIS)

    Nishiyama, Yoshihiro; Yamamoto, Yuka; Monden, Toshihide; Sasakawa, Yasuhiro; Satoh, Katashi; Ohkawa, Motoomi; Kawai, Nobuyuki

    2007-01-01

    The purpose of this study was to investigate the accumulation of FDG in immunocompetent patients with primary central nervous system (CNS) lymphoma using qualitative and quantitative PET images and to compare baseline with follow-up PET after therapy. Twelve immunocompetent patients with CNS lymphoma were examined. Dynamic emission data were acquired for 60 min immediately following injection of FDG. In seven patients, repeated PET studies were performed after treatment. Applying a three-compartment five-parameter model, K 1 , k 2 , k 3 , k 4 , vascular fraction (V B ) and cerebral metabolic rate of glucose (CMR Glc ) were obtained. We evaluated the FDG uptake visually using qualitative and parametric images and quantitatively using parametric images. A total of 12 lesions were identified in ten patients with newly diagnosed CNS lymphoma. On visual analysis, ten lesions showed an increase on qualitative images, eight showed an increase on K 1 images, 12 showed an increase on k 3 images and ten showed an increase on CMR Glc images. On quantitative analysis, k 2 , k 3 and CMR Glc values of the lesion were significantly different from those of the normal grey matter (p 3 and CMR Glc images. The K 1 , k 2 , k 3 and CMR Glc values after treatment were significantly different from those obtained before treatment (p 3 , using dynamic FDG PET might be helpful for diagnosis of CNS lymphoma and for monitoring therapeutic assessment. (orig.)

  17. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Kuziel, William A; Rivest, Serge

    2003-01-01

    Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...

  18. Lateness to School Remediation Game

    Science.gov (United States)

    Ugwuegbulam, Charles N.; Ibrahim, Haj. Naheed

    2015-01-01

    Primary and secondary school in Nigeria encourage punctuality to school yet a good number of the learners came late to school. This is especially true in the case of day students. Learners who come late to school are usually punished in one way or the other yet the lateness to school phenomenon still persist. Lateness to school behaviour affects…

  19. Enhancing Psychosocial Outcomes for Young Adult Childhood CNS Cancer Survivors: Importance of Addressing Vocational Identity and Community Integration

    Science.gov (United States)

    Strauser, David R.; Wagner, Stacia; Wong, Alex W. K.

    2012-01-01

    The purpose of this study was to examine the relationship between vocational identity, community integration, positive and negative affect, and satisfaction with life in a group of young adult central nervous system (CNS) cancer survivors. Participants in this study included 45 young adult CNS cancer survivors who ranged in age from 18 to 30 years…

  20. Distribution of CNS Species on Teat Skin and in Milk Samples from Dairy Cows in Automatic Milking Systems

    DEFF Research Database (Denmark)

    Mahmmod, Yasser; Svennesen, Line; Pedersen, Karl

    identified in milk samples. Staphylococcus chromogenes was detected in both milk (n= 2) and teat skin (n= 1) samples. Data collection will be finished in April 2017. The final results will give new insights into herd specific CNS species patterns and the microbial ecology and epidemiology of common CNS...

  1. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)

    2014-05-15

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  2. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    International Nuclear Information System (INIS)

    Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

    2014-01-01

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  3. Late prematurity: a systematic review

    Directory of Open Access Journals (Sweden)

    Luís Carlos Machado, Júnior

    2014-05-01

    Full Text Available Objective: this study aimed to review the literature regarding late preterm births (34 weeks to 36 weeks and 6 days of gestation in its several aspects. Sources: the MEDLINE, LILACS, and Cochrane Library databases were searched, and the references of the articles retrieved were also used, with no limit of time. Data synthesis: numerous studies showed a recent increase in late preterm births. In all series, late preterm comprised the majority of preterm births. Studies including millions of births showed a strong association between late preterm birth and neonatal mortality. A higher mortality in childhood and among young adults was also observed. Many studies found an association with several neonatal complications, and also with long-term disorders and sequelae: breastfeeding problems, cerebral palsy, asthma in childhood, poor school performance, schizophrenia, and young adult diabetes. Some authors propose strategies to reduce late preterm birth, or to improve neonatal outcome: use of antenatal corticosteroids, changes in some of the guidelines for early delivery in high-risk pregnancies, and changes in neonatal care for this group. Conclusions: numerous studies show greater mortality and morbidity in late preterm infants compared with term infants, in addition to long-term disorders. More recent studies evaluated strategies to improve the outcomes of these neonates. Further studies on these strategies are needed. Resumo: Objetivo: revisar a literatura sobre prematuridade tardia (nascimentos de 34 semanas a 36 semanas e seis dias em seus vários aspectos. Fonte dos dados: buscas nas bases MEDLINE, LILACS e Biblioteca Cochrane, sem limite de tempo, e nas referências bibliográficas dos artigos encontrados. Síntese dos dados: muitos estudos mostram aumento na taxa de prematuridade tardia nos últimos anos. Em todas as séries, os prematuros tardios correspondem à maioria dos nascimentos prematuros. Estudos envolvendo análises de milhões de

  4. P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

    Science.gov (United States)

    Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

    2014-01-01

    The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

  5. Discrimination of different brain metastases and primary CNS lymphomas using morphologic criteria and diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bette, S.; Wiestler, B.; Huber, T.; Boeckh-Behrens, T.; Zimmer, C.; Kirschke, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuroradiology; Delbridge, C. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuropathology; Meyer, B.; Gempt, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neurosurgery

    2016-12-15

    Brain metastases are a common complication of cancer and occur in about 15-40% of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADC{sub lymphoma} 0.92 [0.83-1.07] vs. ADC{sub no} {sub lymphoma} 1.35 [1.10-1.64] P=0.001). Further differentiation between types of metastases was not possible using FA and ADC. There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis.

  6. SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury

    Directory of Open Access Journals (Sweden)

    Emma V. Jones

    2018-02-01

    Full Text Available The proper formation and maintenance of functional synapses in the central nervous system (CNS requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood. Interestingly, SPARC has been shown to be upregulated in CNS injury and disease. However, the role of SPARC upregulation in these contexts is not fully understood. In this study, we investigated the effect of chronic SPARC administration on glutamate receptors on mature hippocampal neuron cultures and following CNS injury. We found that SPARC treatment increased the number of GluA1-containing AMPARs at synapses and enhanced synaptic function. Furthermore, we determined that the increase in synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of SPARC treatment on neuronal health in an injury context where SPARC expression is upregulated. We found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion (MCAO in vivo and oxygen-glucose deprivation (OGD in vitro. Remarkably, chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors. Taken together, this study suggests a novel role for SPARC and GluA1 in promoting neuronal health and recovery following CNS damage.

  7. Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

    Science.gov (United States)

    Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

    2016-10-01

    Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

  8. Ketamine displaces the novel NMDA receptor SPET probe [123I]CNS-1261 in humans in vivo

    International Nuclear Information System (INIS)

    Stone, James M.; Erlandsson, Kjell; Arstad, Erik; Bressan, Rodrigo A.; Squassante, Lisa; Teneggi, Vincenza; Ell, Peter J.; Pilowsky, Lyn S.

    2006-01-01

    [ 123 I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [ 123 I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [ 123 I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [ 123 I]CNS-1261 V T in most of the brain regions examined (P 123 I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site

  9. Ketamine displaces the novel NMDA receptor SPET probe [{sup 123}I]CNS-1261 in humans in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Stone, James M. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom)]. E-mail: j.stone@iop.kcl.ac.uk; Erlandsson, Kjell [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Arstad, Erik [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Bressan, Rodrigo A. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Squassante, Lisa [GlaxoSmithKline (GSK), Verona 37135 (Italy); Teneggi, Vincenza [GlaxoSmithKline (GSK), Verona 37135 (Italy); Ell, Peter J. [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Pilowsky, Lyn S. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom)

    2006-02-15

    [{sup 123}I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [{sup 123}I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [{sup 123}I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [{sup 123}I]CNS-1261 V {sub T} in most of the brain regions examined (P<.05). [{sup 123}I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site.

  10. Late effecten van kankerbehandeling

    NARCIS (Netherlands)

    Langeveld, Nelia E.

    2004-01-01

    In dit artikel wordt ingegaan op de lange termijn effecten van kanker op de kinderleeftijd. Vervolgens wordt een kort overzicht gegeven van de belangrijkste late gevolgen die kunnen optreden na een oncologische behandeling met radio- en/of chemotherapie toegepast in de kinderleeftijd. Er wordt kort

  11. Late-modern hipsters

    DEFF Research Database (Denmark)

    Andersen, Bjørn Schiermer

    2014-01-01

    The article deals with the cultural significance of a new figure in late-modern Western culture: the hipster. The current hipster culture, so I argue, can be used as a magnifying glass that makes impending changes to our conception of culture and of cultural development visible. It ushers...

  12. Big Java late objects

    CERN Document Server

    Horstmann, Cay S

    2012-01-01

    Big Java: Late Objects is a comprehensive introduction to Java and computer programming, which focuses on the principles of programming, software engineering, and effective learning. It is designed for a two-semester first course in programming for computer science students.

  13. Late Embryogenesis Abundant Proteins

    NARCIS (Netherlands)

    Shih, M.D.; Hoekstra, F.A.; Hsing, Y.I.C.

    2008-01-01

    During the late maturation stage of seed development, water content decreases greatly. One of the most striking characteristics of mature orthodox seeds is their ability to withstand severe desiccation. Mechanisms of plant drought/desiccation tolerance have been studied by numerous groups, and a

  14. Quantification of late complications after radiation therapy

    International Nuclear Information System (INIS)

    Jung, Horst; Beck-Bornholdt, Hans-Peter; Svoboda, Vladimir; Alberti, Winfried; Herrmann, Thomas

    2001-01-01

    Background: An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. Methods: Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15x2 Gy (range, 20-40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. Results: Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p a was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p a remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same (p a =10-14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). Discussion: Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time

  15. Persistent Epstein-Barr viral load in Epstein-Barr viral naïve pediatric heart transplant recipients: Risk of late-onset post-transplant lymphoproliferative disease.

    Science.gov (United States)

    Das, Bibhuti; Morrow, Robert; Huang, Rong; Fixler, David

    2016-12-24

    To examine the risk of late-onset post-transplant lymphoproliferative disorder (PTLD) in the presence of persisting high Epstein-Barr virus (EBV) in EBV naïve pediatric heart transplant (HT) recipients. A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. PTLD was diagnosed in 8 out of 145 patients (5.5%); 6/91 (6.5%) in those who were EBV seropositive and 2/54 (3.7%) in the EBV naïve group at the time of HT ( P = 0.71). We found 32/145 (22%) patients with persistently high EBV load during continuing follow-up; 20/91 (22%) in EBV seropositive group vs 12/54 (22%) in EBV naïve group ( P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant ( P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15% (3/20) of patients with high EBV vs 4.2% (3/71) of patients with low or undetectable EBV load ( P = 0.14) whereas in EBV naïve patients 8.3% (1/12) of those with high EBV load and 2.3% (1/42) with low or undetectable EBV load ( P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up (4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort ( P = 0.005). At least one episode of acute rejection occurred in 72% (23/32) of patients with high EBV vs 36% (41/113) patients with low or undetectable EBV after HT ( P < 0.05). There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in

  16. Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling

    International Nuclear Information System (INIS)

    Lumen, A; George, N I

    2017-01-01

    The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher. - Highlights: • Probabilistic risk assessment for perchlorate in U.S. pregnant women was conducted. • No significant change in maternal fT4 predicted due to perchlorate from food alone. • Drinking water concentration allowance for perchlorate estimated as 7.6–9.2 μg/L

  17. Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lumen, A, E-mail: Annie.Lumen@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-110, Jefferson, AR 72079 (United States); George, N I, E-mail: Nysia.George@fda.hhs.gov [Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-20, Jefferson, AR 72079 (United States)

    2017-05-01

    The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher. - Highlights: • Probabilistic risk assessment for perchlorate in U.S. pregnant women was conducted. • No significant change in maternal fT4 predicted due to perchlorate from food alone. • Drinking water concentration allowance for perchlorate estimated as 7.6–9.2 μg/L.

  18. Late-Onset Asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2017-01-01

    Late-onset asthma is common, associated with poor outcome, underdiagnosed and undertreated, possibly due to the modifying effect of ageing on disease expression. Although the diagnostic work-up in elderly individuals suspected of having asthma follows the same steps as in younger individuals (case......, to objectively confirm asthma. If necessary, a trial of oral or inhaled corticosteroid might be necessary. Asthma can be diagnosed when increased airflow variability is identified in a symptomatic patient, and if the patient does not have a history of exposure, primarily smoking, known to cause chronic...... obstructive pulmonary disease, the diagnosis is asthma even if the patient does not have fully reversible airflow obstruction. Pharmacological therapy in patients with late-onset asthma follows international guidelines, including treatment with the lowest effective dose of inhaled corticosteroid to minimize...

  19. Late Babylonian Astrology

    Science.gov (United States)

    Steele, John M.

    The last five centuries BC saw the development of several new forms of astrology in Babylonia. Key to these new astrological techniques was the invention of the zodiac in about 400 BC. These new forms of astrology include personal horoscopes, astral medicine, and the exploitation of geometrical relationships between the position of heavenly bodies. Several Late Babylonian astrological doctrines were later adopted within Greek astrology.

  20. Late Palaeozoic plants.

    Science.gov (United States)

    Feng, Zhuo

    2017-09-11

    Land plants are one of the major constituents of terrestrial ecosystems on Earth, and play an irreplaceable role in human activities today. If we are to understand the extant plants, it is imperative that we have some understanding of the fossil plants from the deep geological past, particularly those that occurred during their early evolutionary history, in the late Palaeozoic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

    Science.gov (United States)

    de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

    2017-06-01

    Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

  2. The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

    Science.gov (United States)

    Forbes, Lindsey H.

    2018-01-01

    The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury. PMID:29849554

  3. Risk

    Science.gov (United States)

    Cole, Stephen R.; Hudgens, Michael G.; Brookhart, M. Alan; Westreich, Daniel

    2015-01-01

    The epidemiologist primarily studies transitions between states of health and disease. The purpose of the present article is to define a foundational parameter for such studies, namely risk. We begin simply and build to the setting in which there is more than 1 event type (i.e., competing risks or competing events), as well as more than 1 treatment or exposure level of interest. In the presence of competing events, the risks are a set of counterfactual cumulative incidence functions for each treatment. These risks can be depicted visually and summarized numerically. We use an example from the study of human immunodeficiency virus to illustrate concepts. PMID:25660080

  4. CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

    Directory of Open Access Journals (Sweden)

    Christine M Matullo

    2011-12-01

    Full Text Available Although viruses have been implicated in central nervous system (CNS diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV and peripherally restricted lymphocytic choriomeningitis virus (LCMV. While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35% of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

  5. Late to the Game

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Kettinger, William J.

    2015-01-01

    This article introduces a framework for assessing IT integration risk in acquisitions. We illustrate the framework’s merits for the management of high-risk acquisitions and identification of low-risk acquisitions with the experience of Trelleborg AB, a global industrial company with acquisitions ...

  6. A lack of cerebral lateralization in schizophrenia is within the normal variation in brain maturation but indicates late, slow maturation.

    Science.gov (United States)

    Saugstad, L F

    1999-10-19

    The planum temporale (PT) bias, PT leftward, PT symmetry, and PT rightward reversal and sidedness preference, consistent right-handedness, ambilaterality, and consistent left-handedness are placed on a continuum mirroring the normal variation in rate of brain maturation. Maturational rate declines as we pass from PT leftward bias and consistent right-handedness to PT reversal and consistent left-handedness. Concomitantly, we expect an increased prevalence of males due to their pubertal age being about 2 years later than that of females, and a shift in cognitive profile from higher verbal scores than performance scores on the WAIS to higher performance than verbal scores. Three disorders fulfilling the criteria of late CNS maturation apart from the corresponding cognitive profile were studied: infantile autism (IA), schizophrenia (S), and developmental dyslexia (DD). These disorders have in common deficits in cognition, perception, and somatomotor function. The deficits range from an arrest in brain development (which is evident in infancy superimposed on late maturation in IA) to overall delayed brain and somatic development in S (culminating in postpubertal psychotic episodes and persistent and generalized residual deficits). Finally, reading inability, problems in perception (vision and hearing) and in motor coordination, particularly between the two hemispheres, characterize DD. Enhancing brain maturation and the prevalence of 'normal' cerebral asymmetry--laterality is preferable if we want to reduce the risk of developing the above-mentioned disorders. It is suggested that in the past environmental challenges have favored early maturation, with its abundant neuronal population, arborization and excessive density of synapses and cerebral excitability which has powered evolution through the mechanism of natural selection. Early maturation is obtainable through optimal nutrition, including a satisfactory amount of marine fat (PUFA), before and during pregnancy and

  7. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Fabio Cavaliere

    2016-01-01

    Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

  8. Inflammatory cytokines in the brain: does the CNS shape immune responses?

    Science.gov (United States)

    Owens, T; Renno, T; Taupin, V; Krakowski, M

    1994-12-01

    Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far from being an immunologically privileged organ, T lymphocytes may be regular and frequent visitors to the CNS, for purposes of immune surveillance. Here, Trevor Owens and colleagues propose that the brain itself can regulate or shape immune responses therein. Furthermore, given that the immune cells may be subverted to autoimmunity, they suggest that the study of inflammatory autoimmune disease in the brain may shed light on the ability of the local environment to regulate immune responses.

  9. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, C.E. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)]. E-mail: chockycj@yahoo.co.uk; Turnbull, I.W. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)

    2006-05-15

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences.

  10. Peroxisome Proliferator-Activated Receptors (PPARs as Potential Inducers of Antineoplastic Effects in CNS Tumors

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS. The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

  11. The glymphatic system in CNS health and disease: past, present and future

    Science.gov (United States)

    Plog, Benjamin A.; Nedergaard, Maiken

    2018-01-01

    The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here we review the role of the glymphatic pathway in CNS physiology, factors known to regulate glymphatic flow, and pathologic processes where a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, will also be discussed. PMID:29195051

  12. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    International Nuclear Information System (INIS)

    Offiah, C.E.; Turnbull, I.W.

    2006-01-01

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences

  13. Evaluation of CNS activities of aerial parts of Cynodon dactylon Pers. in mice.

    Science.gov (United States)

    Pal, Dilipkumar

    2008-01-01

    The dried extracts of aerial parts of Cynodon dactylon Pers. (Graminae) were evaluated for CNS activities in mice. The ethanol extract of aerial parts of C. dactylon (EECD) was found to cause significant depression in general behavioral profiles in mice. EECD significantly potentiated the sleeping time in mice induced by standard hypnotics viz. pentobarbitone sodium, diazepam, and meprobamate in a dose dependant manner. EECD showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. EECD inhibited the onset and the incidence of convulsion in a dose dependent manner against pentylenetetrazole (PTZ)-induced convulsion. The present study indicates that EECD has significant CNS depressant activities.

  14. CNS manifestation in progressive facial hemiatrophy (Romberg's disease). MRI findings and review of the literature

    International Nuclear Information System (INIS)

    Terstegge, K.; Henkes, H.; Kern, A.

    1993-01-01

    In this article the authors describe the clinical and MR imaging findings of the CNS in three female patients with PFH and present a comprehensive review of the literature. One of three PFH patients had partial epilepsy. MRI showed ventricular enlargement, white matter lesions, flattening of the cortical surface and meningeal adhesions homolateral to the facial hemiatrophy. Two other patients had completely normal intracranial findings. These findings confirm that cerebral hemiatrophy can occur in a subgroup of PFH patients. The MRI pattern, however, does not seem to be consistent with a simple atrophic or malnutrition process. The authors consider chronic localized meningoencephalitis with vascular involvement as a possible underlying mechanism for the occasional CNS involvement in PFH. (orig./MG) [de

  15. Coping – Late Side Effects

    Science.gov (United States)

    Cancer treatment can cause late side effects that may not show up for months or years after treatment. These late effects may include heart and lung problems, bone loss, eye and hearing changes, lymphedema, and other problems

  16. Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

    2007-01-01

    to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

  17. Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI

    International Nuclear Information System (INIS)

    Taets ven Amerongen, A.H.M.; Kaiser, M.C.; Waal, F.C. de

    1987-01-01

    A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted an MRI appearance allowing us to exclude tumor outgrowth into the brain. (orig.)

  18. Rotorcraft Low Altitude CNS (Communications, Navigation and Surveillance) Benefit/Cost Analysis, Rotorcraft Operations Data

    Science.gov (United States)

    1989-09-01

    inventory of rotorcraft activity by mission and location. 17. Key Words 18. Distribution Statement Helicopter Helicopter Missions This document is available...helicopter is used to transport skiers /hikers to remote, normally inaccessible places. This mission is performed in rural or wilderness areas at altitudes...their applicability to the CNS benefit/cost analysis. Because of the uncertainty in the knowledge of the characteristics of both current and future

  19. Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Taets ven Amerongen, A.H.M.; Kaiser, M.C.; Waal, F.C. de

    1987-03-01

    A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted an MRI appearance allowing us to exclude tumor outgrowth into the brain.

  20. BOBATH THERAPY IN CORRECTION OF PSYCHOMOTOR DEVELOPMENT OF CHILDREN WITH ORGANIC INJURIES CNS

    OpenAIRE

    Bukhovets, B. O.; Romanchuk, A. P.

    2014-01-01

    The article represents therapy of Bobath such as one of the most effective author method which use in correction psychomotor development of children with disorders of musculoskeletal system. Bobath method is not new in the correction of movement disorders since last century and still supplementing and improving. In this work highlight topic of the effective use Bobath therapy in correction of psychomotor development in children age 3 – 6 years with organic involvement CNS. the experiment w...

  1. The glymphatic system in CNS health and disease: past, present and future

    OpenAIRE

    Plog, Benjamin A.; Nedergaard, Maiken

    2018-01-01

    The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and th...

  2. Nanomaterials for delivery of nucleic acid to the central nervous system (CNS)

    DEFF Research Database (Denmark)

    Wang, Danyang; Wu, Lin-Ping

    2017-01-01

    -related disease, such as neurodegeneration and disorders, suitable, safe and effective drug delivery nanocarriers have to been developed to overcome the blood brain barrier (BBB), which is the most inflexible barrier in human body. Here, we highlight the structure and function of barriers in the central nervous...... system (CNS) and summary several types of nanomaterials which can be potentially used in the brain delivery nucleic acid....

  3. Clinical significance of late high-degree atrioventricular block in patients with left ventricular dysfunction after an acute myocardial infarction--a Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) substudy

    DEFF Research Database (Denmark)

    Gang, Uffe Jakob Ortved; Jøns, Christian; Jørgensen, Rikke Mørch

    2011-01-01

    High-degree atrioventricular block (HAVB) is a frequent complication in the acute stages of a myocardial infarction associated with an increased rate of mortality. However, the incidence and clinical significance of HAVB in late convalescent phases of an AMI is largely unknown. The aim of this st...... of this study was to assess the incidence and prognostic value of late HAVB documented by continuous electrocardiogram (ECG) monitoring in post-AMI patients with reduced left ventricular function....

  4. Prospective evaluation of delayed central nervous system (CNS) toxicity of hyperfractionated total body irradiation (TBI)

    International Nuclear Information System (INIS)

    Wenz, Frederik; Steinvorth, Sarah; Lohr, Frank; Fruehauf, Stefan; Wildermuth, Susanne; Kampen, Michael van; Wannenmacher, Michael

    2000-01-01

    Purpose: Prospective evaluation of chronic radiation effects on the healthy adult brain using neuropsychological testing of intelligence, attention, and memory. Methods and Materials: 58 patients (43 ± 10 yr) undergoing hyperfractionated total body irradiation (TBI) (TBI, 14.4 Gy, 12 x 1.2 Gy in 4 days) before bone marrow or peripheral blood stem cell transplantation were prospectively included. Twenty-one recurrence-free long-term survivors were re-examined 6-36 months (median 27 months) after completion of TBI. Neuropsychological testing included assessment of general intelligence, attention, and memory using normative, standardized psychometric tests. Mood status was controlled, as well. Test results are given as IQ scores (population mean 100) or percentiles for attention and memory (population mean 50). Results: The 21 patients showed normal baseline test results of IQ (101 ± 13) and attention (53 ± 28), with memory test scores below average (35 ± 21). Test results of IQ (98 ± 17), attention (58 ± 27), and memory (43 ± 28) showed no signs of clinically measurable radiation damage to higher CNS (central nervous system) functions during the follow-up. The mood status was improved. Conclusion: The investigation of CNS toxicity after hyperfractionated TBI showed no deterioration of test results in adult recurrence-free patients with tumor-free CNS. The median follow-up of 27 months will be extended.

  5. Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.

    Directory of Open Access Journals (Sweden)

    Roberta Noseda

    2016-04-01

    Full Text Available Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS and central nervous system (CNS myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1, a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K/v-AKT murine thymoma viral oncogene homolog (AKT pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.

  6. Optimization of dipeptidic inhibitors of cathepsin L for improved Toxoplasma gondii selectivity and CNS permeability.

    Science.gov (United States)

    Zwicker, Jeffery D; Diaz, Nicolas A; Guerra, Alfredo J; Kirchhoff, Paul D; Wen, Bo; Sun, Duxin; Carruthers, Vern B; Larsen, Scott D

    2018-06-01

    The neurotropic protozoan Toxoplasma gondii is the second leading cause of death due to foodborne illness in the US, and has been designated as one of five neglected parasitic infections by the Center for Disease Control and Prevention. Currently, no treatment options exist for the chronic dormant-phase Toxoplasma infection in the central nervous system (CNS). T. gondii cathepsin L (TgCPL) has recently been implicated as a novel viable target for the treatment of chronic toxoplasmosis. In this study, we report the first body of SAR work aimed at developing potent inhibitors of TgCPL with selectivity vs the human cathepsin L. Starting from a known inhibitor of human cathepsin L, and guided by structure-based design, we were able to modulate the selectivity for Toxoplasma vs human CPL by nearly 50-fold while modifying physiochemical properties to be more favorable for metabolic stability and CNS penetrance. The overall potency of our inhibitors towards TgCPL was improved from 2 μM to as low as 110 nM and we successfully demonstrated that an optimized analog 18b is capable of crossing the BBB (0.5 brain/plasma). This work is an important first step toward development of a CNS-penetrant probe to validate TgCPL as a feasible target for the treatment of chronic toxoplasmosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. BRAINSTEM AUDITORY EVOKED POTENTIAL AS AN INDEX OF CNS DEMYELINATION IN GUILLAIN -BARRÉ SYNDROME (GBS

    Directory of Open Access Journals (Sweden)

    Smita Singh

    2016-01-01

    Full Text Available Background: Guillain-Barré Syndrome (GBS is an acute, frequently severe and fulminant polyradicular neuropathy that is autoimmune in nature. GBS manifest as rapidly evolving areflexic motor paralysis with or without sensory disturbances. It mainly involves peripheral nervous system and autonomic nervous system. There are rare evidences about the involvement of central nervous system (CNS in GBS. Aims: The main objective of the study was to assess the CNS involvement in GBS using the Brainstem Auditory Evoked Potential (BAEP. Methods & Material: The study was conducted in the clinical neurophysiology lab in the department of physiology, CSMMU Lucknow. Study group involved 26 subjects (n=26 having GBS and control group involved 30 normal subjects (n=30. BAEPS were recorded by Neuroperfect- EMG 2000 EMG/NCV/EPsytem. The data so obtained were subjected to analysis using Statistical Package for Social Sciences (SPSS Version 13.0. Results & Conclusions: There was significant increase in PIII & PV peak latencies and PI-PIII & PI-PV interpeak latencies in both left and right ear in the study group, which showed the CNS involvement in GBS which can be assessed using BAEP.

  8. Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

    Directory of Open Access Journals (Sweden)

    Wilson Pak-Kin Lou

    2018-01-01

    Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

  9. Risk

    Science.gov (United States)

    Barshi, Immanuel

    2016-01-01

    Speaking up, i.e. expressing ones concerns, is a critical piece of effective communication. Yet, we see many situations in which crew members have concerns and still remain silent. Why would that be the case? And how can we assess the risks of speaking up vs. the risks of keeping silent? And once we do make up our minds to speak up, how should we go about it? Our workshop aims to answer these questions, and to provide us all with practical tools for effective risk assessment and effective speaking-up strategies..

  10. Late Washing efficiency

    International Nuclear Information System (INIS)

    Morrissey, M.F.

    1992-01-01

    Interim Waste Technology has demonstrated the Late Washing concept on the Experimental Laboratory Filter (ELF) at TNX. In two tests, washing reduced the [NO 2 - ] from 0.08 M to approximately 0.01 M on slurries with 2 year equivalent radiation exposures and 9.5 wt. % solids. For both washes, the [NO 2 - ] decreased at rates near theoretical for a constant volume stirred vessel, indicating approximately l00% washing efficiency. Permeate flux was greater than 0.05 gpm/ft 2 for both washes at a transmembrane pressure of 50 psi and flow velocity of 9 ft/sec

  11. Late-onset hypogonadism

    Directory of Open Access Journals (Sweden)

    Piotr Dudek

    2017-06-01

    Full Text Available In Poland, the number of men over the age of 50 years exceeds 6 million. It is estimated that about 2-6% of this population develops symptoms of late-onset hypogonadism (LOH. In men, testosterone deficiency increases slightly with age. LOH is a clinically and biochemically defined disease of older men with serum testosterone level below the reference parameters of younger healthy men and with symptoms of testosterone deficiency, manifested by pronounced disturbances of quality of life and harmful effects on multiple organ systems. Testosterone replacement therapy may give several benefits regarding body composition, metabolic control, and psychological and sexual parameters.

  12. Late somatic sequelae after treatment of childhood cancer in Slovenia

    Directory of Open Access Journals (Sweden)

    Erman Nuša

    2012-05-01

    Full Text Available Abstract Background This is a long-term follow-up clinical study of adolescents and adults, survivors of childhood cancer. We evaluate and analyze the late somatic sequelae of childhood cancer treatment. Many such studies are susceptible to a strong selection bias, i.e., they employ a limited non-systematic sample of patients, based on a clinical hospital that provided the cancer treatment or performed the follow-up. To address the issue of selection bias, we perform here an analysis of late sequelae on a systematic database of the entire population of the children treated for cancer in Slovenia. Due to the specifics of cancer treatment procedures in Slovenia, they have all been treated and followed-up in the same clinic. Methods The data are based on the centralized registry of cancer patients in Slovenia and present a controlled and homogeneous collection. Late sequelae are evaluated following a modified CTCAE, i.e., the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3.0. We use survival analysis method to estimate the incidence of and risk for late sequelae, where the time variable is measured in years from the diagnosis date, while we follow the event of incidence of late sequelae scored other than none. Survival analysis is performed using KaplanMeier estimator and Cox regression model. Results The incidence of mild, moderate, or severe late sequelae of childhood cancer treatment significantly decreased from 75% in the group of patients diagnosed before 1975 to 55% for those diagnosed after 1995. The Cox regression analysis of the risk factors for the incidence of late sequelae identifies three significant factors: treatment modalities, age at diagnosis, and primary diagnosis. Conclusions The change of treatment modalities in terms of replacement of surgery and radiotherapy with chemotherapy is the main reason for the decrease of the incidence and the risk for late sequelae of childhood cancer treatment

  13. Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

    DEFF Research Database (Denmark)

    Hassan-Zahraee, M; Tran, E H; Bourbonnière, L

    2000-01-01

    but levels were higher in IFNgamma transgenics. BM transplantation into IFNgamma-deficient recipients also had a high failure rate. Transplants of BM from mice lacking expression of IFNgamma-receptor failed, whereas IFNgamma-deficient grafts survived, suggesting that IFNgamma response status of the graft can......Bone marrow transplantation (BMT) is increasingly used to treat Multiple Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNgamma levels. We wished to determine the effect of IFNgamma on BM graft survival in a transgenic mouse model for chronic MS. BM transplantation...... into transgenic mice which express elevated levels of IFNgamma in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFalpha in the CNS, using the same MBP promoter. IFNgamma was detectable in spleen of irradiated mice...

  14. Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report.

    Science.gov (United States)

    Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian

    2018-05-30

    Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.

  15. Prevalence of Different Combinations of Antiepileptic Drugs and CNS Drugs in Elderly Home Care Service and Nursing Home Patients in Norway.

    Science.gov (United States)

    Halvorsen, Kjell H; Johannessen Landmark, Cecilie; Granas, Anne Gerd

    2016-01-01

    Introduction. Antiepileptic drugs (AEDs) are used to treat different conditions in elderly patients and are among the drug classes most susceptible to be involved in drug-drug interactions (DDI). The aim of the study was to describe and compare use of AEDs between home care service and nursing home patients, as these patients are not included in nationwide databases of drug utilization. In the combined population, we investigate DDI of AEDs with other central nervous system- (CNS-) active drugs and DDIs involving AEDs in general. Materials and Methods. Point-prevalence study of Norwegian patients in home care services and nursing homes in 2009. At the patient level, we screened for different DDIs involving AEDs. Results. In total, 882 patients (7.8%) of 11,254 patients used AEDs and number of users did not differ between home care services and nursing homes (8.2% versus 7.7%). In the combined population, we identified 436 potential DDIs in 45% of the patients. Conclusions. In a large population of elderly, home care service and nursing home patients do not differ with respect to exposure of AEDs but use more AEDs as compared to the general population of similar age. The risk of DDIs with AEDs and other CNS-active drugs should be taken into consideration and individual clinical evaluations are assessed in this population.

  16. Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma

    OpenAIRE

    2008-01-01

    Abstract Patients with malignant central nervous system (CNS) involvement of lymphoma have a poor prognosis with intrathecal chemotherapy and radiation. In this paper, we report the results we obtained in such patients by intravenous chemotherapy with high-dose methotrexate and ifosfamide (HDMTX/IFO). The study involved a review of all patients who received HDMTX/IFO for CNS involvement of malignant lymphoma at our hospital. Therapy consisted of 4 g/m2 of MTX (4 h infu...

  17. Tailored central nervous system-directed treatment strategy for isolated CNS recurrence of adult acute myeloid leukemia.

    Science.gov (United States)

    Zheng, Changcheng; Liu, Xin; Zhu, Weibo; Cai, Xiaoyan; Wu, Jingsheng; Sun, Zimin

    2014-06-01

    The aim of this report was to investigate the tailored treatment strategies for isolated central nervous system (CNS) recurrence in adult patients with acute myeloid leukemia (AML). Isolated CNS recurrence was documented in 34 patients: there were 18, 6, and 10 patients with meningeal involvement type (type A), cranial nerve palsy type (type B), and myeloid sarcoma type (type C), respectively. For patients with type A, intrathecal chemotherapy was the predominant strategy. For type B, systemic HD-Ara-C with four cycles was the main treatment. For type C, cranial irradiation or craniospinal irradiation was adopted and two cycles of HD-Ara-C were given after the irradiation. The 5-year cumulative incidence of CNS recurrence was 12.8%. There was a significantly higher WBC count (32.6∼60.8 × 10(9)/l) in patients at first diagnosis who developed CNS recurrence (all of the three types) compared with patients with no CNS recurrence (10.1 × 10(9)/l) (P = 0.005). We found that a significantly more patients with AML-M5 and 11q23 abnormalities developed CNS recurrence in type A (P adult AML, but further studies are needed to improve the long-term survival.

  18. A Novel Robust H∞ Filter Based on Krein Space Theory in the SINS/CNS Attitude Reference System

    Directory of Open Access Journals (Sweden)

    Fei Yu

    2016-03-01

    Full Text Available Owing to their numerous merits, such as compact, autonomous and independence, the strapdown inertial navigation system (SINS and celestial navigation system (CNS can be used in marine applications. What is more, due to the complementary navigation information obtained from two different kinds of sensors, the accuracy of the SINS/CNS integrated navigation system can be enhanced availably. Thus, the SINS/CNS system is widely used in the marine navigation field. However, the CNS is easily interfered with by the surroundings, which will lead to the output being discontinuous. Thus, the uncertainty problem caused by the lost measurement will reduce the system accuracy. In this paper, a robust H∞ filter based on the Krein space theory is proposed. The Krein space theory is introduced firstly, and then, the linear state and observation models of the SINS/CNS integrated navigation system are established reasonably. By taking the uncertainty problem into account, in this paper, a new robust H∞ filter is proposed to improve the robustness of the integrated system. At last, this new robust filter based on the Krein space theory is estimated by numerical simulations and actual experiments. Additionally, the simulation and experiment results and analysis show that the attitude errors can be reduced by utilizing the proposed robust filter effectively when the measurements are missing discontinuous. Compared to the traditional Kalman filter (KF method, the accuracy of the SINS/CNS integrated system is improved, verifying the robustness and the availability of the proposed robust H∞ filter.

  19. Evaluation of calcium, magnesium, zinc, aluminum and manganese deposition in bones and CNS of rats fed calcium-deficient diets

    International Nuclear Information System (INIS)

    Yasui, Masayuki; Ota, Kiichiro; Sasajima, Kazuhisa; Iwata, Shiro.

    1994-01-01

    The long term intake of unbalanced mineral diets has been reported to be one of the pathogenetic factors of central nervous system (CNS) degeneration, and the unbalanced mineral distribution in the bones clinically is expressed as a metabolic bone disorder or deposition of neurotoxic minerals/metals. The unbalanced mineral or metal diets in animals provoke the unbalanced mineral distribution in bones and soft tissues. In this study, the calcium (Ca), magnesium (Mg), zinc (Zn), aluminum (Al) and manganese (Mn) contents in the CNS and the bones of rats maintained on unbalanced mineral diets were analyzed to investigate the roles of bone on CNS degeneration. Male Wistar rats were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. Al and Mn contents were determined in the frontal cortex, spinal cord, lumbar spine and femur using inductively coupled plasma emission spectrometry (ICP) for Ca, Mg and Zn, and neutron activation analysis (NAA) for Al and Mn. Intake of low Ca and Mg with added Al in rats led to the abnormal distribution of metals or minerals in the bones and in the CNS. These results illustrate that unbalanced mineral diets and metal-metal interactions may lead to the irregular deposition of Al and Mn in the bones and ultimately in the CNS, thus inducing CNS degeneration. (author)

  20. Reproductive rights: Current issues of late abortion

    Directory of Open Access Journals (Sweden)

    Mujović-Zornić Hajrija

    2009-01-01

    Full Text Available This article considers the legal issues surrounding induced late abortion in cases when severe medical, therapeutic or ethical reasons have not been in dispute. Generally discussing the essential question about abortion today, it means not anymore legality of abortion but, in the first place, safety of abortion. From the aspect of woman health the most important aim is to detect and avoid possible risks of medical intervention, such as late abortion present. This is the matter of medical law context and also the matter of the woman's reproductive rights, here observed through legislation and court practice. The gynecologist has an obligation to obtain the informed consent of each patient. Information's should be presented in reasonably understandable terms and include alternative modes of treatment, objectives, risks, benefits, possible complications, and anticipated results of such treatment. Pregnant woman should receive supportive counseling before and particularly after the procedure. The method chosen for all terminations should ensure that the fetus is born dead. This should be undertaken by an appropriately trained practitioner. Reform in abortion law, making it legally accessible to woman, is not necessarily the product of a belief in woman's rights, but can be a means of bringing the practice of abortion back under better control. Counseling and good medical practice in performing late abortion are the instruments to drive this point even further home. It does not undermine the woman who wants to make a positive decision about her life and its purpose is not to produce feelings of insecurity and guilt. It concludes that existing law should not be changed but that clear rules should be devised and board created to review late term abortion. In Serbia, this leads to creation and set up guidelines for reconciling medical justification for late abortion with existing law, especially with solutions which brings comparative law. .

  1. Prevalence and Morbidity of Late Preterm Infants: Current Status in a Medical Center of Northern Taiwan

    Directory of Open Access Journals (Sweden)

    Ming-Luen Tsai

    2012-06-01

    Conclusion: Late-preterm infants have increased risk of neonatal morbidities associated with organ immaturity. The results of this study emphasize the importance of judicious obstetrical decision-making when considering late preterm delivery, and the need to set up anticipatory clinical guidelines for the care of late preterm infants.

  2. Late effects of cancer therapy on the central nervous system

    International Nuclear Information System (INIS)

    Kramer, J.; Moore, I.M.

    1989-01-01

    The number of studies documenting the long-term morbidity of CNS treatment has increased dramatically in recent years. Cranial irradiation, in particular, has been associated with cognitive deficits and neuroanatomic pathology. Children who are treated at an early age and individuals who receive higher doses (2,400 cGy or greater) appear to be at greatest risk for these sequelae. Much more research on the pathogenesis of delayed injury following CNS treatment is needed. Although several compelling mechanisms have been proposed, little empirical evidence is available. This knowledge is essential to the identification of agents that may protect normal brain tissue from injury. Even less is known about the effects of age at time of treatment, type of treatment (radiation v chemotherapy), or dose of radiation in relation to delayed injury. Of utmost importance are studies that will establish the predictive relationship between brain injury and cognitive deficits. This would allow clinicians to predict patients who are at risk for cognitive impairment in order to institute appropriate preventive or remedial interventions.65 references

  3. Late-Modern Symbolism

    DEFF Research Database (Denmark)

    Andersen, Bjørn Schiermer

    2015-01-01

    Through analysis of key texts, I seek to demonstrate the explanative potential of Durkheim’s sociology of religion in the present context. I critically readdress the idea, found in his early work, that modernity is characterized by a rupture with pre-modern forms of solidarity. First, I investigate...... the ways in which Durkheim sets up a stark distinction between the pre-modern and the modern in his early work, and how this distinction is further cemented by his orthodox critique of the modern economy and its negative effects on social life. Second, I show how another timeless and positive understanding...... of “mechanical” solidarity is to be found behind the “symbolist” template crystalizing in Durkheim’s late work. Third, I develop this template for a modern context by critically addressing and removing other obstacles and prejudices on Durkheim’s part....

  4. Neurocognitive outcome in young adults born late-preterm.

    Science.gov (United States)

    Heinonen, Kati; Lahti, Jari; Sammallahti, Sara; Wolke, Dieter; Lano, Aulikki; Andersson, Sture; Pesonen, Anu-Katriina; Eriksson, Johan G; Kajantie, Eero; Raikkonen, Katri

    2018-03-01

    This study examined whether late-preterm birth (34+0 to 36+6wks+d gestational age) was associated with neurocognitive deficit in young adulthood, and whether small for gestational age (SGA) birth amplified any adversity. Participants derived from the prospective regional cohort study, the Arvo Ylppö Longitudinal Study (n=786; 398 females, 388 males) (mean age 25y 4mo, SD 8mo), born 1985 to 1986 late-preterm (n=119; 21 SGA, intelligence, executive functioning, attention, and memory, and reported their education. Those born late-preterm scored -3.71 (95% confidence interval [CI] -6.71 to -0.72) and -3.11 (95% CI -6.01 to -0.22) points lower on Full-scale and Verbal IQ than peers born at term. Compared with those born at term and appropriate for gestational age (≥-2 to increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and SGA seems to increase this risk. Late-preterm birth did not increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and being small for gestational age did increase this risk. © 2017 Mac Keith Press.

  5. Leukoencephalopathy following CNS prophylaxis therapy in pediatric leukemia : MR imaging findings

    International Nuclear Information System (INIS)

    Kim, Jong Sub; Lee, Sang Kwon; Kim, Tae Hun; Kim, Yong Joo; Kang, Duck Sik; Kwon, Soon Hak; Lee, Keon Soo

    2001-01-01

    To evaluate the MR imaging findings and the usefulness of MR imaging in the diagnosis and follow-up leukoencephalopathy following CNS prophylaxis therapy in pediatric leukemia. We retrospectively evaluated the MR imaging findings of eight children with white matter abnormalities on MR out of seventeen acute leukemic patients with various neuropsychiatric symptoms who received intrathecal methotrexate administration, with or without cranial irradiation. In all cases, initial MR was performed within a week of the onset of neuropsychiatric symptoms. Follow-up MR was performed one to sixteen months after initial study, and the MR imaging findings were compared with the initial findings. The initial MR imaging findings were classified into three categories : focal or multifocal white matter abnormalities (3/8), and diffuse white matter abnormalities without enhancement (3/8), and diffuse white matter abnormalities with enhancement (2/8). At follow-up MR, diffuse or focal atrophic changes were noted in all children. White matter abnormalities improved in two out of three patients with focal or multifocal white matter abnormalities. In five with diffuse white matter abnormalities, the extent of these showed no significant change, but contrast enhancement was markedly reduced in two children in whom diffuse white matter abnormalities with enhancement had been demonstrated. In pediatric leukemia, the MR imaging findings of leukoencephalopathy following CNS prophylaxis therapy are variable, but are specific with the clinical history of neuropsychiatric symptoms after intrathecal methotrexate administration, with or without cranial irradiation. The MR imaging is valuable in the diagnosis and follow-up of leukoencephalopathy following CNS prophylaxis therapy in pediatric leukemia

  6. Effects of prolonged treatment with memantine in the MRL model of CNS lupus.

    Science.gov (United States)

    Marcinko, Katarina; Parsons, Tiffany; Lerch, Jason P; Sled, John G; Sakic, Boris

    2012-09-01

    Neuropsychiatric manifestations and brain atrophy of unknown etiology are common and severe complications of systemic lupus erythematosus (SLE). An autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been proposed as a key factor in the etiology of central nervous system (CNS) SLE. This hypothesis was supported by evidence suggesting memantine (MEM), an uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain pathology in healthy mice immunized with a peptide similar to an epitope on the NR2 receptor. Given that SLE is a chronic condition, we presently examine the effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE-like disease. A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE. Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

  7. Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice

    Energy Technology Data Exchange (ETDEWEB)

    Farfán-García, E.D.; Pérez-Rodríguez, M. [Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México (Mexico); Espinosa-García, C. [Departamento de Biología de la Reproducción, Universidad Autónoma Metropolitana (UAM), 09310 Ciudad de México (Mexico); Castillo-Mendieta, N.T.; Maldonado-Castro, M.; Querejeta, E.; Trujillo-Ferrara, J.G. [Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México (Mexico); and others

    2016-09-15

    The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥ 200 mg/kg, and involving granular cell damage at doses of 400 mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system. - Highlights: • Intraperitoneal 3-thienylboronic acid (3TB) induces tremor in CD1 or C57BL6 mice. • Injury on CNS as well as motor disruption is dose-dependent. • Damage is greater in basal ganglia than in cerebellum or motor cortex. • The DMSO as vehicle plays a key role in the induced effect. • Motor disruption seems to involve basal ganglia and cerebellum damage.

  8. Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice

    International Nuclear Information System (INIS)

    Farfán-García, E.D.; Pérez-Rodríguez, M.; Espinosa-García, C.; Castillo-Mendieta, N.T.; Maldonado-Castro, M.; Querejeta, E.; Trujillo-Ferrara, J.G.

    2016-01-01

    The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥ 200 mg/kg, and involving granular cell damage at doses of 400 mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system. - Highlights: • Intraperitoneal 3-thienylboronic acid (3TB) induces tremor in CD1 or C57BL6 mice. • Injury on CNS as well as motor disruption is dose-dependent. • Damage is greater in basal ganglia than in cerebellum or motor cortex. • The DMSO as vehicle plays a key role in the induced effect. • Motor disruption seems to involve basal ganglia and cerebellum damage.

  9. Potential Role of Oxidative Stress in mediating the Effect of Hypergravity on the Developing CNS.

    Science.gov (United States)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Sulkowski, Z. L.; Lipinski, B.

    The present studies will explore the mechanisms through which altered gravity affects the developing CNS We have previously shown that exposure to hypergravity during the perinatal period adversely impacts cerebellar structure and function Pregnant rat dams were exposed to 1 65 G on a 24-ft centrifuge at NASA-ARC from gestational day G 5 through giving birth Both dams and their offspring remained at 1 65 G until pups reached postnatal day P 21 Control rats were raised under identical conditions in stationary cages On P21 motor behavior as determined by performance on a rotorod was more negatively impacted in hypergravity-exposed HG male 39 5 than in HG female pups 29 1 The total number of Purkinje cells determined stereologically in cerebella isolated from a subset of P21 rats was decreased in both HG males and HG female pups but the correlation between Purkinje cell number and rotorod performance was more consistent in male pups The level of 3-nitrosotyrosine 3-NT an index of oxidative damage to proteins was determined by ELISA in cerebellar tissue derived from a separate subset of P21 rats The level of 3-NT was increased by 127 in HG males but only 42 in HG females These results suggest that the effect of altered gravity on the developing brain may be mediated by oxidative stress These results also suggest that the developing male CNS may be more sensitive to hypergravity-induced oxidative stress than the developing female CNS Supported by NIEHS grant ES11946-01

  10. The Effect of the Uncariae Ramulus et Uncus on the Regeneration Following CNS Injury

    Directory of Open Access Journals (Sweden)

    Lee Jin-Goo

    2009-03-01

    Full Text Available Objective : Following central nervous system(CNS injury, inhibitory influences at the site of axonal damage occur. Glial cells become reactive and form a glial scar, gliosis. Also myelin debris such as MAG inhibits axonal regeneration. Astrocyte-rich gliosis relates with up-regulation of GFAP and CD81, and eventually becomes physical and mechanical barrier to axonal regeneration. MAG is one of several endogenous axon regeneration inhibitors that limit recovery from CNS injury and disease. It was reported that molecules that block such inhibitors enhanced axon regeneration and functional recovery. Recently it was reported that treatment with anti-CD81 antibodies enhanced functional recovery in the rat with spinal cord injury. So in this current study, the author investigated the effect of the water extract of Uncariae Ramulus et Uncus on the regulation of CD81, GFAP and MAG that increase when gliosis occurs. Methods : MTT assay was performed to examine cell viability, and cell-based ELISA, western blot and PCR were used to detect the expression of CD81, GFAP and MAG. Then also immunohistochemistry was performed to confirm in vivo. Results : Water extract of Uncariae Ramulus et Uncus showed relatively high cell viability at the concentration of 0.05%, 0.1% and 0.5%. The expression of CD81, GFAP and MAG in astrocytes was decreased after the administration of Uncariae Ramulus et Uncus water extract. These results was confirmed in the brain sections following cortical stab injury by immunohistochemistry. Conclusion : The authors observed that Uncariae Ramulus et Uncus significantly down-regulates the expression of CD81, GFAP and MAG. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

  11. Blood-CNS Barrier Impairment in ALS Patients versus an Animal Model

    Directory of Open Access Journals (Sweden)

    Svitlana eGarbuzova-Davis

    2014-02-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a severe neurodegenerative disease with a compli-cated and poorly understood pathogenesis. Recently, alterations in the blood-Central Nervous System barrier (B-CNS-B have been recognized as a key factor possibly aggravating motor neuron damage. The majority of findings on ALS microvascular pathology have been deter-mined in mutant SOD1 rodent models, identifying barrier damage during disease develop-ment which might similarly occur in familial ALS patients carrying the SOD1 mutation. However, our knowledge of B-CNS-B competence in sporadic ALS (SALS has been limited. We recently showed structural and functional impairment in postmortem gray and white mat-ter microvessels of medulla and spinal cord tissue from SALS patients, suggesting pervasive barrier damage. Although numerous signs of barrier impairment (endothelial cell degenera-tion, capillary leakage, perivascular edema, downregulation of tight junction proteins, and microhemorrhages are indicated in both mutant SOD1 animal models of ALS and SALS pa-tients, other pathogenic barrier alterations have as yet only been identified in SALS patients. Pericyte degeneration, perivascular collagen IV expansion, and white matter capillary abnor-malities in SALS patients are significant barrier related pathologies yet to be noted in ALS SOD1 animal models. In the current review, these important differences in blood-CNS barrier damage between ALS patients and animal models, which may signify altered barrier transport mechanisms, are discussed. Understanding discrepancies in barrier condition between ALS patients and animal models may be crucial for developing effective therapies.

  12. Installation and Commissioning of the Helium Refrigeration System for the HANARO-CNS

    International Nuclear Information System (INIS)

    Choi, Jung Woon; Kim, Young Ki; Wu, Sang Ik; Son, Woo Jung

    2009-11-01

    The cold neutron source (CNS), which will be installed in the vertical CN hole of the reflector tank at HANARO, makes thermal neutrons to moderate into the cold neutrons with the ranges of 0.1 ∼ 10 meV passing through a moderator at about 22K. A moderator to produce cold neutrons is liquid hydrogen, which liquefies by the heat transfer with cryogenic helium flowing from the helium refrigeration system. For the maintenance of liquid hydrogen in the IPA, the CNS system is mainly consisted of the hydrogen system to supply the hydrogen to the IPA, the vacuum system to keep the cryogenic liquid hydrogen in the IPA, and the helium refrigeration system to liquefy the hydrogen gas. The helium refrigeration system can be divided into two sections: one is the helium compression part from the low pressure gas to the high pressure gas and the other is the helium expansion part from the high temperature gas and pressure to low temperature and pressure gas by the expansion turbine. The helium refrigeration system except the warm helium pipe and the helium buffer tank has been manufactured by Linde Kryotechnik, AG in Switzerland and installed in the research reactor hall, HANARO. Other components have been manufactured in the domestic company. This technical report deals with the issues, its solutions, and other particular points while the helium refrigeration system was installed at site, verified its performance, and conducted its commissioning along the reactor operation. Furthermore, the operation procedure of the helium refrigeration system is included in here for the normal operation of the CNS

  13. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G

    2008-10-01

    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  14. AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders.

    Science.gov (United States)

    Ivachtchenko, Alexandre V; Lavrovsky, Yan; Okun, Ilya

    2016-05-25

    Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2-2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41-3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer's disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis.

  15. Efficient T-cell surveillance of the CNS requires expression of the CXC chemokine receptor 3

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; Nansen, Anneline; Moos, Torben

    2004-01-01

    T-cells play an important role in controlling viral infections inside the CNS. To study the role of the chemokine receptor CXCR3 in the migration and positioning of virus-specific effector T-cells within the brain, CXCR3-deficient mice were infected intracerebrally with lymphocytic choriomeningitis......-cell-mediated immunopathology. Quantitative analysis of the cellular infiltrate in CSF of infected mice revealed modest, if any, decrease in the number of mononuclear cells recruited to the meninges in the absence of CXCR3. However, immunohistological analysis disclosed a striking impairment of CD8+ T-cells from CXCR3...

  16. CNS changes in Usher's syndrome with mental disorder: CT, MRI and PET findings.

    Science.gov (United States)

    Koizumi, J; Ofuku, K; Sakuma, K; Shiraishi, H; Iio, M; Nawano, S

    1988-01-01

    CNS changes in a case of Usher's syndrome associated with schizophrenia-like mental disorder were observed by CT, MRI and PET. The neuro-radiological findings of the case demonstrate the degenerative and metabolic alterations in various regions of cortex, white matter and subcortical areas in the brain. Mental disorder of the case is almost indistinguishable from that of schizophrenia, but the psychotic feature is regarded as an atypical or mixed organic brain syndrome according to the classification in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Images PMID:3264568

  17. [Regularities of fixation of brain serum antibodies from patients with lateral amyotrophic sclerosis in rabbit CNS].

    Science.gov (United States)

    Musaeva, L S; Gannyshkina, I V; Zavalishin, I A; Markova, E D; Ivanova-Smolenskaia, I A

    2002-01-01

    Kuhns' indirect immunofluorescent test was used to study fixation of serum brain antibodies (Ab) of patients with bulbar, cervicothoracic, lumbosacral lateral amyotropic sclerosis (LAS) on brain sections of rabbits. The disease is characterized by formation of brain Ab complementary to various structures of nervous and glial cells, myelin of fibers from different conducting systems, vessels which exhibit both common and individual antigenic properties. It was found that fixation of antineuronal, antimyelin brain Ab of patients with bulbar, cervicothoracic and lumbosacral LAS in different CNS structures varies.

  18. News from the editors of Fluids and Barriers of the CNS.

    Science.gov (United States)

    Drewes, Lester R; Jones, Hazel C; Keep, Richard F

    2014-01-01

    This editorial announces a new affiliation between Fluids and Barriers of the CNS (FBCNS) and the International Brain Barriers Society (IBBS) with mutual benefits to the journal and to society members. This is a natural progression from the appointment of two new Co-Editors in Chief: Professor Lester Drewes and Professor Richard Keep in 2013. FBCNS provides a unique and specialist platform for the publication of research in the expanding fields of brain barriers and brain fluid systems in both health and disease.

  19. Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS)

    DEFF Research Database (Denmark)

    Asgari, N; Owens, T; Frøkiaer, J

    2010-01-01

    Asgari N, Owens T, Frøkiaer J, Stenager E, Lillevang ST, Kyvik KO. Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS).
Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01416.x.
© 2010 John Wiley & Sons A/S. In the past 10 years, neuromyelitis optica (NMO) has...... or by intrathecal administration to naive mice. NMO may be characterized as a channelopathy of the central nervous system with autoimmune characteristics....

  20. An in vitro clonogenic assay to assess radiation damage in rat CNS glial progenitor cells

    International Nuclear Information System (INIS)

    Maazen, R.W.M. van der; Verhagen, I.; Kogel, A.J. van der

    1990-01-01

    Normal glial progenitor cells can be isolated from the rat central nervous system (CNS) and cultured in vitro on a monolayer of type-1 astrocytes. These monolayers are able to support and stimulate explanted glial progenitor cells to proliferate. Employing these in vitro interactions of specific glial cell types, an in vivo-in vitro clonogenic assay has been developed. This method offers the possibility to study the intrinsic radiosensitivity, repair and regeneration of glial progenitor cells after in vitro or in vivo irradiation. (author)

  1. Late Carboniferous to Late Permian carbon isotope stratigraphy

    DEFF Research Database (Denmark)

    Buggisch, Werner; Krainer, Karl; Schaffhauser, Maria

    2015-01-01

    An integrated study of the litho-, bio-, and isotope stratigraphy of carbonates in the Southern Alps was undertaken in order to better constrain δ13C variations during the Late Carboniferous to Late Permian. The presented high resolution isotope curves are based on 1299 δ13Ccarb and 396 δ13Corg...

  2. Late neurotoxicity after nasopharyngeal carcinoma treatment

    International Nuclear Information System (INIS)

    Siala, W.; Mnejja, W.; Daoud, J.; Khabir, A.; Boudawara, T.; Ben Mahfoudh, K.; Ghorbel, A.; Frikha, M.

    2009-01-01

    Purpose A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy. Patients and methods Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity. Results After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p = 0.02). On multivariate analysis, hyperfractionation and age were insignificant. Conclusion Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study

  3. Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

    Science.gov (United States)

    Nakagawa, Shunsuke; Shinkoda, Yuichi; Hazeki, Daisuke; Imamura, Mari; Okamoto, Yasuhiro; Kawakami, Kiyoshi; Kawano, Yoshifumi

    2016-07-01

    Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

  4. Fluid Induced Vibration Analysis of a Cooling Water Pipeline for the HANARO CNS

    International Nuclear Information System (INIS)

    Kim, Bong Soo; Lee, Young Sub; Kim, Ik Soo; Kim, Young Ki

    2007-01-01

    CNS is the initial of Cold Neutron Source and the CNS facility system consists of hydrogen, a vacuum, a gas blanketing, a helium refrigeration and a cooling water supply system. Out of these subsystems, the helium refrigeration system has the function of removal of heat from a thermal neutron under reactor operation. Therefore, HRS (helium refrigeration system) must be under normal operation for the production of cold neutron. HRS is mainly made up of a helium compressor and a coldbox. This equipment is in need of cooling water to get rid of heat generation under stable operation and a cooling water system is essential to maintain the normal operation of a helium compressor and a coldbox. The main problem for the cooling water system is the vibration issue in the middle of operation due to a water flow in a pipeline. In order to suppress the vibration problem for a pipeline, the characteristics of a pipeline and fluid flow must be analyzed in detail. In this paper, fluid induced vibration of a cooling water pipe is analyzed numerically and the stability of the cooling water pipeline is investigated by using pipe dynamic theory

  5. Extending Injury- and Disease-Resistant CNS Phenotypes by Repetitive Epigenetic Conditioning

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Gidday

    2015-03-01

    Full Text Available Significant reductions in the extent of acute injury in the CNS can be achieved by exposure to different preconditioning stimuli, but the duration of the induced protective phenotype is typically short-lasting, and thus is deemed as limiting its clinical applicability. Extending the period over which such adaptive epigenetic changes persist – in effect, expanding conditioning’s therapeutic window – would significantly broaden the potential applications of such a treatment approach in patients. The frequency of the conditioning stimulus may hold the key. While transient (1-3 days protection against CNS ischemic injury is well established preclinically following a single preconditioning stimulus, repetitively presenting preconditioning stimuli extends the duration of ischemic tolerance by many weeks. Moreover, repetitive intermittent postconditioning enhances postischemic recovery metrics and improves long-term survival. Intermittent conditioning is also efficacious for preventing or delaying injury in preclinical models of chronic neurodegenerative disease, and for promoting long-lasting functional improvements in a number of other pathologies as well. Although the detailed mechanisms underlying these protracted kinds of neuroplasticity remain largely unstudied, accumulating empirical evidence supports the contention that all of these adaptive phenotypes are epigenetically mediated. Going forward, additional preclinical demonstrations of the ability to induce sustained beneficial phenotypes that reduce the burden of acute and chronic neurodegeneration, and experimental interrogations of the regulatory constructs responsible for these epigenetic responses, will accelerate the identification of not only efficacious, but practical, adaptive epigenetics-based treatments for individuals with neurological disease.

  6. Blue moon neurovirology: the merits of studying rare CNS diseases of viral origin.

    Science.gov (United States)

    O'Donnell, Lauren A; Rall, Glenn F

    2010-09-01

    While measles virus (MV) continues to have a significant impact on human health, causing 150,000-200,000 deaths worldwide each year, the number of fatalities that can be attributed to MV-triggered central nervous system (CNS) diseases are on the order of a few hundred individuals annually (World Health Organization 2009). Despite this modest impact, substantial effort has been expended to understand the basis of measles-triggered neuropathogenesis. What can be gained by studying such a rare condition? Simply stated, the wealth of studies in this field have revealed core principles that are relevant to multiple neurotropic pathogens, and that inform the broader field of viral pathogenesis. In recent years, the emergence of powerful in vitro systems, novel animal models, and reverse genetics has enabled insights into the basis of MV persistence, the complexity of MV interactions with neurons and the immune system, and the role of immune and CNS development in virus-triggered disease. In this review, we highlight some key advances, link relevant measles-based studies to the broader disciplines of neurovirology and viral pathogenesis, and propose future areas of study for the field of measles-mediated neurological disease.

  7. Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes.

    Science.gov (United States)

    Kaewpoowat, Quanhathai; Salazar, Lucrecia; Aguilera, Elizabeth; Wootton, Susan H; Hasbun, Rodrigo

    2016-06-01

    To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections. Retrospective review of adult patients with positive HSV or VZV polymerase chain reaction on CSF from an observational study of meningitis or encephalitis in Houston, TX (2004-2014), and New Orleans, LA (1999-2008). Ninety-eight adults patients were identified; 25 had encephalitis [20 (20.4 %) HSV, 5 (5.1 %) VZV], and 73 had meningitis [60 (61.1 %) HSV and 13 (13.3 %) VZV]. HSV and VZV had similar presentations except for nausea (P 1 and an encephalitis presentation were independently associated with an ACO. The treatment for HSV meningitis was variable, and all patients had a good clinical outcome. Alpha herpes CNS infections due to HSV and VZV infections have similar clinical and laboratory manifestations. ACO was observed more frequently in those patients with comorbidities and an encephalitis presentation.

  8. Permanent I-125 interstitial implant in the management of high grade CNS malignancies in children

    International Nuclear Information System (INIS)

    Vaishampayan, N.; Zamorano, L.; Aronin, P.; Gaspar, L.; Canady, A.; Lattin, P.; Ezzell, G.; Yakar, D.; Chungbin, S.; Fontanesi, J.

    1996-01-01

    Purpose/Objective: To evaluate the efficacy and complications associated with the use of permanent I-125 interstitial implants in children with high grade CNS malignancies. Materials and Methods: Between May of 1990 and September of 1994, fourteen children received permanent I-125 interstitial implant brachytherapy as initial therapy (n=8) or at time of recurrence (n=6). Histologies included Glioblastoma Multiforme (n=2), Anaplastic Astrocytoma (n=9) and others (n=3). Pre-implant surgical procedures included: Gross Total Resection (n=2), Subtotal Resection (n=8) or Biopsy alone (n=4). Six patients received pre-implant external beam irradiation (dose range 3,500-6500 cGy) and three patients received post-implant external beam irradiation (dose range 5,040-5,060 cGy). Implant dose range was 8,294-10,368 cGy over the lifetime of the implant (median 10,368 cGy). Results: At last follow-up (median 17.5 months; range 4-56 months), eight children were alive. Six out of the eight had no evidence of disease progression while the remaining had radiologic evidence of progression. Implant complications (n=2) included skin necrosis and bone flap infection. Conclusions: Based on this initial review, we continue to investigate the use of permanent I-125 interstitial brachytherapy in the treatment of high grade CNS malignancies in children and will discuss and compare these results with those of other 'Boost' series

  9. Drug Elucidation: Invertebrate Genetics Sheds New Light on the Molecular Targets of CNS Drugs

    Directory of Open Access Journals (Sweden)

    Donard S. Dwyer

    2014-07-01

    Full Text Available Many important drugs approved to treat common human diseases were discovered by serendipity, without a firm understanding of their modes of action. As a result, the side effects and interactions of these medications are often unpredictable, and there is limited guidance for improving the design of next-generation drugs. Here, we review the innovative use of simple model organisms, especially Caenorhabditis elegans, to gain fresh insights into the complex biological effects of approved CNS medications. Whereas drug discovery involves the identification of new drug targets and lead compounds/biologics, and drug development spans preclinical testing to FDA approval, drug elucidation refers to the process of understanding the mechanisms of action of marketed drugs by studying their novel effects in model organisms. Drug elucidation studies have revealed new pathways affected by antipsychotic drugs, e.g., the insulin signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor. Similarly, novel targets of antidepressant drugs and lithium have been identified in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling pathway, respectively. Elucidation of the mode of action of anesthetic agents has shown that anesthesia can involve mitochondrial targets, leak currents and gap junctions. The general approach reviewed in this article has advanced our knowledge about important drugs for CNS disorders and can guide future drug discovery efforts.

  10. Role of resident CNS cell populations in HTLV-1-associated neuroinflammatory disease.

    Science.gov (United States)

    Lepoutre, Veronique; Jain, Pooja; Quann, Kevin; Wigdahl, Brian; Khan, Zafar K

    2009-01-01

    Human T cell leukemia virus type 1 (HTLV-1), the first human retrovirus discovered, is the etiologic agent for a number of disorders; the two most common pathologies include adult T cell leukemia (ATL) and a progressive demyelinating neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The neurologic dysfunction associated with HAM/TSP is a result of viral intrusion into the central nervous system (CNS) and the generation of a hyperstimulated host response within the peripheral and central nervous system that includes expanded populations of CD4+ and CD8+ T cells and proinflammatory cytokines/chemokines in the cerebrospinal fluid (CSF). This robust, yet detrimental immune response likely contributes to the death of myelin producing oligodendrocytes and degeneration of neuronal axons. The mechanisms of neurological degeneration in HAM/TSP have yet to be fully delineated in vivo and may involve the immunogenic properties of the HTLV-1 transactivator protein Tax. This comprehensive review characterizes the available knowledge to date concerning the effects of HTLV-1 on CNS resident cell populations with emphasis on both viral and host factors contributing to the genesis of HAM/TSP.

  11. CNS Orientations, Safety Objectives and Implementation of the Defence in Depth Concept

    Energy Technology Data Exchange (ETDEWEB)

    Lacoste, A.C., E-mail: Andre-Claude.LACOSTE@asn.fr [Autorité de Sureté Nucléaire, Montrouge (France)

    2014-10-15

    Full text: The 6th Review Meeting of the Convention on Nuclear Safety (CNS) is convened in Vienna next year for two weeks from Monday March 24{sup th} to Friday April 4{sup th} 2014. The consequences and the lessons learnt from the accident that occurred at the Fukushima Daiichi nuclear power plant will be a major issue. The 2nd Extraordinary Meeting of the CNS in August 2012 was totally devoted to the Fukushima Daiichi accident. One of its main conclusions was Conclusion 17 included in the summary report which says: ''Nuclear power plants should be designed, constructed and operated with the objectives of preventing accidents and, should an accident occur, mitigating its effects and avoiding off-site contamination. The Contracting Parties also noted that regulatory authorities should ensure that these objectives are applied in order to identify and implement appropriate safety improvements at existing plants''. The wording of the sentences of Conclusion 17 dedicated, the first one to new built reactors, the second one to existing plants, can be improved and clarified. But obviously the issue of the off-site consequences of an accident is fundamental. So the in-depth question comes: what can and should be done to achieve these safety objectives? And in particular how to improve the definition and then the implementation of the Defence in Depth Concept? From my point of view, this is clearly the main issue of this Conference. (author)

  12. Evidence of end-effector based gait machines in gait rehabilitation after CNS lesion.

    Science.gov (United States)

    Hesse, S; Schattat, N; Mehrholz, J; Werner, C

    2013-01-01

    A task-specific repetitive approach in gait rehabilitation after CNS lesion is well accepted nowadays. To ease the therapists' and patients' physical effort, the past two decades have seen the introduction of gait machines to intensify the amount of gait practice. Two principles have emerged, an exoskeleton- and an endeffector-based approach. Both systems share the harness and the body weight support. With the end-effector-based devices, the patients' feet are positioned on two foot plates, whose movements simulate stance and swing phase. This article provides an overview on the end-effector based machine's effectiveness regarding the restoration of gait. For the electromechanical gait trainer GT I, a meta analysis identified nine controlled trials (RCT) in stroke subjects (n = 568) and were analyzed to detect differences between end-effector-based locomotion + physiotherapy and physiotherapy alone. Patients practising with the machine effected in a superior gait ability (210 out of 319 patients, 65.8% vs. 96 out of 249 patients, 38.6%, respectively, Z = 2.29, p = 0.020), due to a larger training intensity. Only single RCTs have been reported for other devices and etiologies. The introduction of end-effector based gait machines has opened a new succesful chapter in gait rehabilitation after CNS lesion.

  13. [A review of the effects of lithium on cognitive functions: Effects on the neuropsychiatrically challenged CNS].

    Science.gov (United States)

    Tsaltas, E; Kontis, D

    2009-04-01

    Recent data attribute neuroprotective and neurotrophic actions to lithium, leading to expectations of cognitive enhancement action. This hypothesis is at odds with the predominant view of clinical psychiatr y which, on the basis of older clinical data as well as on subjective reports of lithiumtreated patients, associates lithium with cognitive blurring and specific memory deficits. Review of the older data and their integration with more recent clinical and experimental work on the primary effects of lithium on cognitive functioning led us to two central conclusions: (a) Data on the primary cognitive effects of lithium, considered in their entirety, do not support a picture of serious or long-lasting cognitive decline. On the contrary, recent evidence suggests cognitive enhancement under certain conditions. (b) The conditions which appear to promote the emergence of cognitive enhancement under lithium are conditions of challenge to the cognitive systems, such as increased task difficulty resulting in deterioration in the performance of untreated controls. We are suggesting that alternative challenges to cognitive functioning, which therefore would facilitate the emergence of lithium's cognitive enhancement action, include biological insults to the central nervous system (CNS). This second part of our review of the cognitive effects of lithium therefore focuses on studies of its action on cognitive dysfunction associated with functional or biological challenge to the CNS, such as stress, trauma, neurodegenerative and psychiatric disorders.

  14. Evaluation of intrafraction patient movement for CNS and head and neck IMRT