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Sample records for target organs impairment

  1. Model organisms and target discovery.

    Science.gov (United States)

    Muda, Marco; McKenna, Sean

    2004-09-01

    The wealth of information harvested from full genomic sequencing projects has not generated a parallel increase in the number of novel targets for therapeutic intervention. Several pharmaceutical companies have realized that novel drug targets can be identified and validated using simple model organisms. After decades of service in basic research laboratories, yeasts, worms, flies, fishes, and mice are now the cornerstones of modern drug discovery programs.: © 2004 Elsevier Ltd . All rights reserved.

  2. World Health Organization cardiovascular risk stratification and target organ damage.

    Science.gov (United States)

    Piskorz, D; Bongarzoni, L; Citta, L; Citta, N; Citta, P; Keller, L; Mata, L; Tommasi, A

    2016-01-01

    Prediction charts allow treatment to be targeted according to simple markers of cardiovascular risk; many algorithms do not recommend screening asymptomatic target organ damage which could change dramatically the assessment. To demonstrate that target organ damage is present in low cardiovascular risk hypertensive patients and it is more frequent and severe as global cardiovascular risk increases. Consecutive hypertensive patients treated at a single Latin American center. Cardiovascular risk stratified according to 2013 WHO/ISH risk prediction chart America B. Left ventricular mass assessed by Devereux method, left ventricular hypertrophy considered >95g/m(2) in women and >115g/m(2) in men. Transmitral diastolic peak early flow velocity to average septal/lateral peak early diastolic relaxation velocity (E/e' ratio) measured cut off value >13. Systolic function assessed by tissue Doppler average interventricular septum/lateral wall mitral annulus rate systolic excursion (s wave). A total of 292 patients were included of whom 159 patients (54.5%) had cardiovascular risk of 20%. Left ventricular hypertrophy was detected in 17.6% low risk patients, 27.8% in medium risk and 23.3% in high risk (p<0.05), abnormal E/e' ratio was found in 13.8%, 31.1% and 27.9%, respectively (p<0.05). Mean s wave was 8.03+8, 8.1+9 and 8.7+1cm/s for low, intermediate and high risk patients, respectively (p<0.025). Target organ damage is more frequent and severe in high risk; one over four subjects was misclassified due to the presence of asymptomatic target organ damage. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  3. Musical tasks targeting preserved and impaired functions in two dementias.

    Science.gov (United States)

    Halpern, Andrea R; Golden, Hannah L; Magdalinou, Nadia; Witoonpanich, Pirada; Warren, Jason D

    2015-03-01

    Studies of musical abilities in dementia have for the most part been rather general assessments of abilities, for instance, assessing retention of music learned premorbidly. Here, we studied patients with dementias with contrasting cognitive profiles to explore specific aspects of music cognition under challenge. Patients suffered from Alzheimer's disease (AD), in which a primary impairment is in forming new declarative memories, or Lewy body disease (PD/LBD), a type of parkinsonism in which executive impairments are prominent. In the AD patients, we examined musical imagery. Behavioral and neural evidence confirms involvement of perceptual networks in imagery, and these are relatively spared in early stages of the illness. Thus, we expected patients to have relatively intact imagery in a mental pitch comparison task. For the LBD patients, we tested whether executive dysfunction would extend to music. We probed inhibitory skills by asking for a speeded pitch or timbre judgment when the irrelevant dimension was held constant or also changed. Preliminary results show that AD patients score similarly to controls in the imagery tasks, but PD/LBD patients are impaired relative to controls in suppressing some irrelevant musical dimensions, particularly when the required judgment varies from trial to trial. © 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  4. Synthetic lipid nanoparticles targeting steroid organs

    International Nuclear Information System (INIS)

    Merian, Juliette; Boisgard, Raphael; Theze, Benoit; Decleves, Xavier; Texier, Isabelle; Tavitian, Bertrand

    2013-01-01

    Lipidots are original nano-particulate lipid delivery vectors for drugs and contrast agents made from materials generally regarded as safe. Here, we characterized the in vivo stability, biodistribution, and pharmacokinetics of lipidots. Lipidots 55 nm in diameter and coated with a phospholipid/poly(ethyleneglycol) surfactant shell were triply labeled with 3 H-cholesteryl-hexadecyl-ether, cholesteryl- 14 C-oleate, and the 1,19-dioctadecyl-3,3,39,39-tetramethyl-indo-tri-carbocyanine infrared fluorescent dye and injected intravenously into immunocompetent Friend virus B-type mice. The pharmacokinetics and biodistribution of lipidots were analyzed quantitatively in serial samples of blood and tissue and with in vivo optical imaging and were refined by microscopic examination of selected target tissues. The plasmatic half-life of lipidots was approximately 30 min. Radioactive and fluorescent tracers displayed a similar nanoparticle-driven biodistribution, indicative of the lipidots' integrity during the first hours after injection. Lipidots distributed in the liver and, surprisingly, in the steroid-rich organs adrenals and ovaries, but not in the spleen. This tropism was confirmed at the microscopic level by histologic detection of 1,19-dioctadecyl- 3,3,39,39-tetramethyl-indo-tri-carbocyanine. Nanoparticle loading with cholesterol derivatives increased accumulation in ovaries in a dose dependent manner. This previously unreported distribution pattern is specific to lipidots and attributed to their nano-metric size and composition, conferring on them a lipoprotein-like behavior. The affinity of lipidots for steroid hormone-rich areas is of interest to address drugs and contrast agents to lipoprotein-receptor-over-expressing cancer cells found in hormone-dependent tumors. (authors)

  5. Hypertensive target organ damage in Ghanaian civil servants with hypertension.

    Directory of Open Access Journals (Sweden)

    Juliet Addo

    2009-08-01

    Full Text Available Low levels of detection, treatment and control of hypertension have repeatedly been reported from sub Saharan Africa, potentially increasing the likelihood of target organ damage.A cross-sectional study was conducted on 1015 urban civil servants aged > or = 25 years from seven central government ministries in Accra, Ghana. Participants diagnosed to have hypertension were examined for target organ involvement. Hypertensive target organ damage was defined as the detection of any of the following: left ventricular hypertrophy diagnosed by electrocardiogram, reduction in glomerular filtration rate, the presence of hypertensive retinopathy or a history of a stroke.Of the 219 hypertensive participants examined, 104 (47.5% had evidence of target organ damage. The presence of target organ damage was associated with higher systolic and diastolic blood pressure levels. The odds of developing hypertensive target organ damage was five to six times higher in participants with blood pressure (BP > or = 180/110 mmHg compared to those with BP < 140/90 mmHg, and there was a trend to higher odds of target organ damage with increasing BP (p = 0.001. Women had about lower odds of developing target organ damage compared to men.The high prevalence of target organ damage in this working population associated with increasing blood pressure, emphasises the need for hypertension control programs aimed at improving the detection of hypertension, and importantly addressing the issues inhibiting the effective treatment and control of people with hypertension in the population.

  6. Lexical-semantic organization in children with specific language impairment.

    Science.gov (United States)

    Sheng, Li; McGregor, Karla K

    2010-02-01

    To determine whether children with specific language impairment (SLI) show deficits in lexical-semantic organization and, if so, whether these deficits are commensurate with their delay in vocabulary size and whether the deficits affect all children with SLI. Fourteen children with SLI, 14 age matches (AM), and 14 expressive vocabulary matches (VM) generated 3 associations to each of 48 words. Associations were coded as semantic (e.g., dog-pet), clang (e.g., cow-how), or erroneous (e.g., spoon-Disney). Relative to the AM children, children with SLI produced fewer semantic responses, more clangs, and more errors. Relative to the VM children, fewer semantic responses and more errors in the children with SLI were found in by-item analyses. Across elicitation trials, semantic responses decreased in the AM and VM children but remained stable in the SLI children. Examination of individual performance in the SLI group revealed that poor semantic performance was associated with a deficit in expressive vocabulary and a gap between receptive and expressive vocabularies. Significant variability in lexical-semantic organization skills exists among children with SLI. Deficits in lexical-semantic organization were demonstrated by a subgroup of children with SLI who likely had concomitant word-finding difficulties.

  7. Organization and targets of the European Branch

    Energy Technology Data Exchange (ETDEWEB)

    Cataldi, R.

    1997-12-01

    After a short historical review of the formation, objectives and organization of the International Geothermal Association (IGA), this paper describes the functions, goals and activities of the IGA European Branch. In particular, the paper illustrates the plan of action established for the periods 1993-`95 and 1996-`98, and the issues dealt with by the European Forum as of August 1996. The last section of the paper outlines the main problems to be faced in the near future in order to facilitate the aggregation of efforts, the amalgamation of promotional initiatives and the coordination of the basic activities needed for the consolidation and growth of the geothermal community in Europe. (orig.)

  8. Crowding and perceptual organization: Target's objecthood influences the relative strength of part-level and configural-level crowding.

    Science.gov (United States)

    Pirkner, Yossef; Kimchi, Ruth

    2017-09-01

    In visual crowding, identification of a peripheral object is impaired by nearby objects. Recent studies have demonstrated that crowding is not limited only to interaction between low-level features or parts, as presumed by most models of crowding, but can also occur between high-level, configural representations of objects. In this study we show that the relative strength of crowding at the part level versus the configural level is dependent on the strength of the target's perceptual organization. The target's strength of organization was manipulated by presence or absence of closure and good continuation or by proximity between the target's parts. The flankers were similar either to the target parts or to the target configuration. The stronger the target's organization was, the weaker the crowding was by part flankers (Experiments 1 and 2). Most importantly, the target's strength of organization interacted with target-flanker similarity, such that crowding by target-flanker similarity in configuration was greater than that by target-flanker similarity in parts for strongly organized targets, but lesser for weakly organized targets (Experiments 3 and 4). These results provide strong evidence that perceptual-organization processes play an important role in crowding.

  9. Social exclusion impairs distractor suppression but not target enhancement in selective attention.

    Science.gov (United States)

    Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Zhang, Lijie; Yuan, Shuge; Yang, Dong

    2017-11-01

    Social exclusion has been thought to weaken one's ability to exert inhibitory control. Existing studies have primarily focused on the relationship between exclusion and behavioral inhibition, and have reported that exclusion impairs behavioral inhibition. However, whether exclusion also affects selective attention, another important aspect of inhibitory control, remains unknown. Therefore, the current study aimed to explore whether social exclusion impairs selective attention, and to specifically examine its effect on two hypothesized mechanisms of selective attention: target enhancement and distractor suppression. The Cyberball game was used to manipulate social exclusion. Participants then performed a visual search task while event-related potentials were recorded. In the visual search task, target and salient distractor were either both presented laterally or one was presented on the vertical midline and the other laterally. Results showed that social exclusion differentially affected target and distractor processing. While exclusion impaired distractor suppression, reflected as smaller distractor-positivity (Pd) amplitudes for the exclusion group compared to the inclusion group, it did not affect target enhancement, reflected as similar target-negativity (Nt) amplitudes for both the exclusion and inclusion groups. Together, these results extend our understanding of the relationship between exclusion and inhibitory control, and suggest that social exclusion affects selective attention in a more complex manner than previously thought. Copyright © 2017. Published by Elsevier B.V.

  10. [A search of target regions for association studies between DNA methylation and cognitive impairment in schizophrenia].

    Science.gov (United States)

    Kondratiev, N V; Alfimova, M V; Golimbet, V E

    To develop a strategy for the search for candidate genes and targets for epigenetic studies of cognitive impairments in patients with schizophrenia. A search for literature on epigenetics of schizophrenia and cognitive functions was performed. Single nucleotide polymorphisms (SNPs) that can create or abolish a site for DNA methylation or transcription factor sites were determined using a custom script. Eight candidate genes, including BDNF, COMT, RELN, SNRPN, PSMA4, FAM63B, IL-1RAP, MAD1L1, as well as 750 targets in CpG islands in the linkage regions identified in GWAS of schizophrenia and 406 targets in SNV located within transcription factor binding sites were selected.

  11. A Single Unexpected Change in Target- but Not Distractor Motion Impairs Multiple Object Tracking

    Directory of Open Access Journals (Sweden)

    Hauke S. Meyerhoff

    2013-02-01

    Full Text Available Recent research addresses the question whether motion information of multiple objects contributes to maintaining a selection of objects across a period of motion. Here, we investigate whether target and/or distractor motion information is used during attentive tracking. We asked participants to track four objects and changed either the motion direction of targets, the motion direction of distractors, neither, or both during a brief flash in the middle of a tracking interval. We observed that a single direction change of targets is sufficient to impair tracking performance. In contrast, changing the motion direction of distractors had no effect on performance. This indicates that target- but not distractor motion information is evaluated during tracking.

  12. Targeting the monocyte-macrophage lineage in solid organ transplantation

    NARCIS (Netherlands)

    T.P.P. van den Bosch (Thierry); Kannegieter, N.M. (Nynke M.); D.A. Hesselink (Dennis); C.C. Baan (Carla); A.T. Rowshani (Ajda)

    2017-01-01

    textabstractThere is an unmet clinical need for immunotherapeutic strategies that specifically target the active immune cells participating in the process of rejection after solid organ transplantation. The monocyte-macrophage cell lineage is increasingly recognized as a major player in acute and

  13. Target Organ Damage And Associated Clinical Conditions In Newly ...

    African Journals Online (AJOL)

    Failure to detect and make a diagnosis of hypertension leads to late presentation and institution of treatment with consequent development of target organ damage (TOD) and associated clinical conditions (ACC) which in turn are associated with increased cost of treatment, morbidity and mortality. Objective: This study was ...

  14. Serum uric acid and target organ damage in essential hypertension.

    Science.gov (United States)

    Ofori, Sandra N; Odia, Osaretin J

    2014-01-01

    Hypertension is a major risk factor for cardiovascular mortality, as it acts through its effects on target organs, such as the heart and kidneys. Hyperuricemia increases cardiovascular risk in patients with hypertension. To assess the relationship between serum uric acid and target organ damage (left ventricular hypertrophy and microalbuminuria) in untreated patients with essential hypertension. A cross-sectional study was carried out in 130 (85 females, 45 males) newly diagnosed, untreated patients with essential hypertension. Sixty-five healthy age- and sex-matched non-hypertensive individuals served as controls for comparison. Left ventricular hypertrophy was evaluated by cardiac ultrasound scan, and microalbuminuria was assessed in an early morning midstream urine sample by immunoturbidimetry. Blood samples were collected for assessing uric acid levels. Mean serum uric acid was significantly higher among the patients with hypertension (379.7±109.2 μmol/L) than in the controls (296.9±89.8 μmol/L; P<0.001), and the prevalence of hyperuricemia was 46.9% among the hypertensive patients and 16.9% among the controls (P<0.001). Among the hypertensive patients, microalbuminuria was present in 54.1% of those with hyperuricemia and in 24.6% of those with normal uric acid levels (P=0.001). Similarly, left ventricular hypertrophy was more common in the hypertensive patients with hyperuricemia (70.5% versus 42.0%, respectively; P=0.001). There was a significant linear relationship between mean uric acid levels and the number of target organ damage (none versus one versus two: P=0.012). These results indicate that serum uric acid is associated with target organ damage in patients with hypertension, even at the time of diagnosis; thus, it is a reliable marker of cardiovascular damage in our patient population.

  15. Serum uric acid and target organ damage in essential hypertension

    Directory of Open Access Journals (Sweden)

    Ofori SN

    2014-05-01

    Full Text Available Sandra N Ofori, Osaretin J OdiaDepartment of Internal Medicine, University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, NigeriaBackground: Hypertension is a major risk factor for cardiovascular mortality, as it acts through its effects on target organs, such as the heart and kidneys. Hyperuricemia increases cardiovascular risk in patients with hypertension.Objective: To assess the relationship between serum uric acid and target organ damage (left ventricular hypertrophy and microalbuminuria in untreated patients with essential hypertension.Patients and methods: A cross-sectional study was carried out in 130 (85 females, 45 males newly diagnosed, untreated patients with essential hypertension. Sixty-five healthy age- and sex-matched non-hypertensive individuals served as controls for comparison. Left ventricular hypertrophy was evaluated by cardiac ultrasound scan, and microalbuminuria was assessed in an early morning midstream urine sample by immunoturbidimetry. Blood samples were collected for assessing uric acid levels.Results: Mean serum uric acid was significantly higher among the patients with hypertension (379.7±109.2 µmol/L than in the controls (296.9±89.8 µmol/L; P<0.001, and the prevalence of hyperuricemia was 46.9% among the hypertensive patients and 16.9% among the controls (P<0.001. Among the hypertensive patients, microalbuminuria was present in 54.1% of those with hyperuricemia and in 24.6% of those with normal uric acid levels (P=0.001. Similarly, left ventricular hypertrophy was more common in the hypertensive patients with hyperuricemia (70.5% versus 42.0%, respectively; P=0.001. There was a significant linear relationship between mean uric acid levels and the number of target organ damage (none versus one versus two: P=0.012.Conclusion: These results indicate that serum uric acid is associated with target organ damage in patients with hypertension, even at the time of diagnosis; thus, it is a reliable

  16. Hope for children and families: targeting abusive parenting and the associated impairment of children.

    Science.gov (United States)

    Bentovim, Arnon; Elliott, Ian

    2014-01-01

    The purpose of this study is to distill the "effective practice elements" from randomised controlled interventions (RCTs) to prevent the recurrence of abusive and neglectful parenting and the associated health and developmental impairment of children. The resulting elements would be used then to develop a step-by-step modular-systemic approach to intervention that is suitable to the needs of a variety of frontline practitioners in social care, health, and education. A series of 22 randomised RCTs were analysed using the distillation and matching approach to establish the presence of effective practice elements. The focus was physical and sexual abuse, victims and children, and young people as perpetrators; neglect including failure to thrive, emotional abuse (exposure to violence and mental health issues). The studies were analysed for effective practice elements, across different approaches matched to interventions focused on parenting, on children and young people, and on family/professional relationships. The proportion of practice elements utilised in each form of maltreatment was defined. The distillation process resulted in a total of 47 practice elements present across all forms of maltreatment studied. An experienced group of practitioners from statutory and voluntary agencies ordered and integrated the most frequently utilised emerging elements into a series of step-by-step modules, which could fit the complex needs of families when maltreatment had occurred. The resulting manual, Hope for Children and Families, provides a "menu" of evidence-based, step-by-step modular interventions targeting the profile of abusive and neglectful parenting and associated impairments of children. To be effective for frontline practitioners, the manual will need to be delivered in a user-friendly format, training developed, and supervision and support provided.

  17. Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer.

    Science.gov (United States)

    Yang, Fei; Gao, Jun-Yi; Chen, Hua; Du, Zhen-Hua; Zhang, Xue-Qun; Gao, Wei

    2017-01-01

    Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim) were also detected. We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 μM) and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer.

  18. Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.

    Science.gov (United States)

    Demyanenko, Ilya A; Popova, Ekaterina N; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Romashchenko, Valeria P; Fedorov, Artem V; Manskikh, Vasily N; Skulachev, Maxim V; Zinovkin, Roman A; Pletjushkina, Olga Yu; Skulachev, Vladimir P; Chernyak, Boris V

    2015-07-01

    The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlierin vitro. The Transforming Growth Factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.

  19. Hypertensive Cardiovascular and Renal Disease and Target Organ Damage: Lessons from Animal Models

    Science.gov (United States)

    Susic, Dinko; Frohlich, Edward D.

    2011-01-01

    This brief review discusses some aspects of hypertensive damage to the kidneys and cardiovascular system. A comparison of renal and cardiac manifestations of hypertensive disease between results of clinical and experimental studies was made, with a major focus on the possible role of salt and the renin-angiotensin system (RAS) in inducing target organ damage. Thus, some degree of renal impairment is often present in patients with essential hypertension, varying from microalbuminuria to end-stage renal disease, whereas in rats with spontaneous hypertension only slight renal damage is seen in old rats with little evidence of renal failure. Since renal damage in hypertensive rats is induced when they are exposed to increased salt intake, we suggested that salt may also account for kidney injury in hypertensive patients. Similarly, cardiac damage is aggravated in hypertensive human beings and rats when given salt excess. We further presented evidence that the RAS may mediate adverse cardiac and renal effects of excessive salt intake. Finally, we also discussed some aspects of the cardiovascular physiology in the giraffe, the only mammal that in comparison with the human being has extremely high pressure at the level of the heart and kidneys but no target organ damage. PMID:22258536

  20. Vitamin D depletion aggravates hypertension and target-organ damage

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine

    2015-01-01

    BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P....6±3.3 versus 162.3±3.8 mm Hg, PVitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and r...

  1. Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis.

    Science.gov (United States)

    Kwak, T; Drews-Elger, K; Ergonul, A; Miller, P C; Braley, A; Hwang, G H; Zhao, D; Besser, A; Yamamoto, Y; Yamamoto, H; El-Ashry, D; Slingerland, J M; Lippman, M E; Hudson, B I

    2017-03-01

    The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to-mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth. RAGE knockdown with multiple independent shRNAs in breast cancer cells led to decreased transwell invasion and soft agar colony formation, without affecting proliferation. In vivo, targeting RAGE shRNA knockdown in human and mouse breast cancer cells, decreased orthotopic tumor growth, reduced tumor angiogenesis and recruitment of inflammatory cells, and markedly decreased metastasis to the lung and liver in multiple xenograft and syngeneic mouse models. To test the non-tumor cell microenvironment role of RAGE, we performed syngeneic studies with orthotopically injected breast cancer cells in wild-type and RAGE-knockout C57BL6 mice. RAGE-knockout mice displayed striking impairment of tumor cell growth compared with wild-type mice, along with decreased mitogen-activated protein kinase signaling, tumor angiogenesis and inflammatory cell recruitment. To test the combined inhibition of RAGE in both tumor cell-intrinsic and non-tumor cells of the microenvironment, we performed in vivo treatment of xenografted tumors with FPS-ZM1 (1 mg/kg, two times per week). Compared with vehicle, FPS-ZM1 inhibited primary tumor growth, inhibited tumor angiogenesis and inflammatory cell recruitment and, most importantly, prevented metastasis to the lung and liver. These data demonstrate that RAGE drives tumor

  2. Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer

    Directory of Open Access Journals (Sweden)

    Yang F

    2017-09-01

    Full Text Available Fei Yang,1,* Jun-Yi Gao,2,* Hua Chen,1 Zhen-Hua Du,1 Xue-Qun Zhang,3 Wei Gao4 1Department of Pathology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 2Department of Clinical Medicine, Weifang Medical College, Weifang, 3Graduate School, Taishan Medical University, Xintai, 4Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. Methods: In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim were also detected. Results: We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 µM and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Conclusion: Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer. Keywords: human colon cancer, PI3K/Akt/mTOR pathway, BEZ235, PI3KCA knockdown

  3. Shared effects of organic microcontaminants and environmental stressors on biofilms and invertebrates in impaired rivers

    International Nuclear Information System (INIS)

    Sabater, S.; Barceló, D.; De Castro-Català, N.; Ginebreda, A.; Kuzmanovic, M.; Petrovic, M.; Picó, Y.; Ponsatí, L.; Tornés, E.; Muñoz, I.

    2016-01-01

    Land use type, physical and chemical stressors, and organic microcontaminants were investigated for their effects on the biological communities (biofilms and invertebrates) in several Mediterranean rivers. The diversity of invertebrates, and the scores of the first principal component of a PCA performed with the diatom communities were the best descriptors of the distribution patterns of the biological communities against the river stressors. These two metrics decreased according to the progressive site impairment (associated to higher area of agricultural and urban-industrial, high water conductivity, higher dissolved organic carbon and dissolved inorganic nitrogen concentrations, and higher concentration of organic microcontaminants, particularly pharmaceutical and industrial compounds). The variance partition analyses (RDAs) attributed the major share (10%) of the biological communities' response to the environmental stressors (nutrients, altered discharge, dissolved organic matter), followed by the land use occupation (6%) and of the organic microcontaminants (2%). However, the variance shared by the three groups of descriptors was very high (41%), indicating that their simultaneous occurrence determined most of the variation in the biological communities. - Highlights: • River impairment was associated to increasing agricultural and urban-industrial areas, and sites were having waters with high water conductivity and nutrient concentrations, and higher concentrations of organic microcontaminants, particularly pharmaceutical and alkylphenol compounds. • Physico-chemical stressors (high nutrients and dissolved organic matter, altered water flow) were the ones mostly affecting biodiversity. • The simultaneous occurrence of microcontaminants with physico-chemical stressors in urban-industrial areas produced a much higher effect than the simple addition of stressors. - Organic microcontaminants reinforce the effects of environmental and land use

  4. Impairment-targeted exercises for older adults with knee pain: protocol for a proof-of-principle study

    Directory of Open Access Journals (Sweden)

    Thomas Elaine

    2011-01-01

    Full Text Available Abstract Background Exercise therapy for knee pain and osteoarthritis remains a key element of conservative treatment, recommended in clinical guidelines. Yet systematic reviews point to only modest benefits from exercise interventions. One reason for this might be that clinical trials tend to use a one-size-fits-all approach to exercise, effectively disregarding the details of their participants' clinical presentations. This uncontrolled before-after study (TargET-Knee-Pain aims to test the principle that exercises targeted at the specific physical impairments of older adults with knee pain may be able to significantly improve those impairments. It is a first step towards testing the effectiveness of this more individually-tailored approach. Methods/Design We aim to recruit 60 participants from an existing observational cohort of community-dwelling older adults with knee pain. Participants will all have at least one of the three physical impairments of weak quadriceps, a reduced range of knee flexion and poor standing balance. Each participant will be asked to undertake a programme of exercises, targeted at their particular combination and degree of impairment(s, over the course of twelve weeks. The exercises will be taught and progressed by an experienced physiotherapist, with reference to a "menu" of agreed exercises for each of the impairments, over the course of six fortnightly home visits, alternating with six fortnightly telephone calls. Primary outcome measures will be isometric quadriceps strength, knee flexion range of motion, timed single-leg standing balance and the "Four Balance Test Scale" at 12 weeks. Key secondary outcome measures will be self-reported levels of pain, stiffness and difficulties with day-to-day functional tasks (WOMAC. Outcome measures will be taken at three time-points (baseline, six weeks and twelve weeks by a study nurse blinded to the exercise status of the participants. Discussion This study (Targ

  5. Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia.

    Science.gov (United States)

    Takei, Kunio; Yamasue, Hidenori; Abe, Osamu; Yamada, Haruyasu; Inoue, Hideyuki; Suga, Motomu; Sekita, Kayoko; Sasaki, Hiroki; Rogers, Mark; Aoki, Shigeki; Kasai, Kiyoto

    2008-08-01

    The fornix is a major projection of the hippocampus to and from other brain regions. A previous diffusion tensor imaging (DTI) study has reported disrupted integrity of the fornix in patients with schizophrenia. However, functional significance of the DTI abnormalities of the fornix in schizophrenia has not been fully studied yet. We investigated an association between DTI abnormalities of the fornix and impairment of memory organization in schizophrenia. Thirty-one patients with schizophrenia and 65 age- and gender-matched healthy controls underwent DTI, and fractional anisotropy (FA) and mean diffusivity (MD) were measured in cross-sections of fornix tractography. In addition, all of the patients and 32 controls performed a verbal learning task specialized for evaluating memory organization, the verbal memory subscale of the Wechsler Memory Scale-Revised, the category- and letter fluency tests, and the Japanese version of National Adult Reading Test. Statistically significant reduction of FA and increase of MD were found in the fornix of patients with schizophrenia compared with controls with no significant lateralization. A significant patients-specific correlation was found between increased MD in the left fornix and lower scores on utilization of semantic organization in the verbal learning task. In addition, increased MD in the right fornix showed a patients-specific association with poorer performance on the category fluency test, which indexes organization of long-term semantic memory. These patients-specific correlations, however, were not statistically lateralized to either hemisphere. These results indicate that disrupted integrity of the fornix contributes to impaired memory organization in schizophrenia.

  6. Competency modeling targeted on promotion of organizations towards VO involvement

    NARCIS (Netherlands)

    Ermilova, E.; Afsarmanesh, H.

    2008-01-01

    During the last decades, a number of models is introduced in research, addressing different perspectives of the organizations’ competencies in collaborative networks. This paper introduces the "4C-model", developed to address competencies of organizations, involved in Virtual organizations Breeding

  7. Shared effects of organic microcontaminants and environmental stressors on biofilms and invertebrates in impaired rivers.

    Science.gov (United States)

    Sabater, S; Barceló, D; De Castro-Català, N; Ginebreda, A; Kuzmanovic, M; Petrovic, M; Picó, Y; Ponsatí, L; Tornés, E; Muñoz, I

    2016-03-01

    Land use type, physical and chemical stressors, and organic microcontaminants were investigated for their effects on the biological communities (biofilms and invertebrates) in several Mediterranean rivers. The diversity of invertebrates, and the scores of the first principal component of a PCA performed with the diatom communities were the best descriptors of the distribution patterns of the biological communities against the river stressors. These two metrics decreased according to the progressive site impairment (associated to higher area of agricultural and urban-industrial, high water conductivity, higher dissolved organic carbon and dissolved inorganic nitrogen concentrations, and higher concentration of organic microcontaminants, particularly pharmaceutical and industrial compounds). The variance partition analyses (RDAs) attributed the major share (10%) of the biological communities' response to the environmental stressors (nutrients, altered discharge, dissolved organic matter), followed by the land use occupation (6%) and of the organic microcontaminants (2%). However, the variance shared by the three groups of descriptors was very high (41%), indicating that their simultaneous occurrence determined most of the variation in the biological communities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Fearful contextual expression impairs the encoding and recognition of target faces: an ERP study

    Directory of Open Access Journals (Sweden)

    Huiyan eLin

    2015-09-01

    Full Text Available Previous event-related potential (ERP studies have shown that the N170 to faces is modulated by the emotion of the face and its context. However, it is unclear how the encoding of emotional target faces as reflected in the N170 is modulated by the preceding contextual facial expression when temporal onset and identity of target faces are unpredictable. In addition, no study as yet has investigated whether contextual facial expression modulates later recognition of target faces. To address these issues, participants in the present study were asked to identify target faces (fearful or neutral that were presented after a sequence of fearful or neutral contextual faces. The number of sequential contextual faces was random and contextual and target faces were of different identities so that temporal onset and identity of target faces were unpredictable. Electroencephalography (EEG data was recorded during the encoding phase. Subsequently, participants had to perform an unexpected old/new recognition task in which target face identities were presented in either the encoded or the non-encoded expression. ERP data showed a reduced N170 to target faces in fearful as compared to neutral context regardless of target facial expression. In the later recognition phase, recognition rates were reduced for target faces in the encoded expression when they had been encountered in fearful as compared to neutral context. The present findings suggest that fearful compared to neutral contextual faces reduce the allocation of attentional resources towards target faces, which results in limited encoding and recognition of target faces.

  9. Plasma Lipid Profile and Target Organ Effect of Theobromine ...

    African Journals Online (AJOL)

    The influence of theobromine rich extracts of cocoa on plasma lipid profile and its organ specific effects on the kidney and liver were determined in twenty female weaning albino wistar rats. Varying concentration, 70 mg/kg, 140 mg/kg and 210 mg/kg body weight of theobromine in 0.9% normal saline were administered ...

  10. Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function.

    Science.gov (United States)

    Armstrong, Patrick A; Wood, Scott J; Shimizu, Naoki; Kuster, Kael; Perachio, Adrian; Makishima, Tomoko

    2015-06-01

    Genetically engineered mice are valuable models for elucidation of auditory and vestibular pathology. Our goal was to establish a comprehensive vestibular function testing system in mice using: (1) horizontal angular vestibulo-ocular reflex (hVOR) to evaluate semicircular canal function and (2) otolith-ocular reflex (OOR) to evaluate otolith organ function and to validate the system by characterizing mice with vestibular dysfunction. We used pseudo off-vertical axis rotation to induce an otolith-only stimulus using a custom-made centrifuge. For the OOR, horizontal slow-phase eye velocity and vertical eye position were evaluated as a function of acceleration. Using this system, we characterized hVOR and OOR in the caspase-3 (Casp3) mutant mice. Casp3 (-/-) mice had severely impaired hVOR gain, while Casp3 (+/-) mice had an intermediate response compared to WT mice. Evaluation of OOR revealed that at low-to-mid frequencies and stimulus intensity, Casp3 mutants and WT mice had similar responses. At higher frequencies and stimulus intensity, the Casp3 mutants displayed mildly reduced otolith organ-related responses. These findings suggest that the Casp3 gene is important for the proper function of the semicircular canals but less important for the otolith organ function.

  11. Preserved otolith organ function in caspase-3 deficient mice with impaired horizontal semicircular canal function

    Science.gov (United States)

    Armstrong, Patrick A; Wood, Scott J; Shimizu, Naoki; Kuster, Kael; Perachio, Adrian; Makishima, Tomoko

    2015-01-01

    Genetically engineered mice are valuable models for elucidation of auditory and vestibular pathology. Our goal was to establish a comprehensive vestibular function testing system in mice using: 1) horizontal angular vestibular-ocular reflex (hVOR) to evaluate semicircular canal function, and 2) otolith-ocular reflex (OOR) to evaluate otolith organ function, and to validate the system by characterizing mice with vestibular dysfunction. We used pseudo-off vertical axis rotation (pOVAR) to induce an otolith-only stimulus using a custom-made centrifuge. For the OOR, horizontal slow phase eye velocity (HEV) and vertical eye position (VEP) was evaluated as a function of acceleration. Using this system, we characterized hVOR and OOR in the caspase-3 (Casp3) mutant mice. Casp3 −/− mice had severely impaired hVOR gain, while Casp3 +/− mice had an intermediate response compared to WT mice. Evaluation of OOR revealed that at low to mid frequencies and stimulus intensity, Casp3 mutants and WT mice had similar responses. At higher frequencies and stimulus intensity, the Casp3 mutants displayed mildly reduced otolith organ related responses. These findings suggest that the Casp3 gene is important for the proper function of the semicircular canals but less important for the otolith organ function. PMID:25827332

  12. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth.

    Science.gov (United States)

    Barbie, Thanh U; Alexe, Gabriela; Aref, Amir R; Li, Shunqiang; Zhu, Zehua; Zhang, Xiuli; Imamura, Yu; Thai, Tran C; Huang, Ying; Bowden, Michaela; Herndon, John; Cohoon, Travis J; Fleming, Timothy; Tamayo, Pablo; Mesirov, Jill P; Ogino, Shuji; Wong, Kwok-Kin; Ellis, Matthew J; Hahn, William C; Barbie, David A; Gillanders, William E

    2014-12-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-κB and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds.

  13. Hypertensive crisis. Clinical presentation, comorbidities, and target organ involvement.

    Science.gov (United States)

    Al-Bannay, Rashed; Husain, Aysha A

    2010-08-01

    To evaluate the clinical presentation and comorbidities of hypertensive crisis in our own population. In this cohort based study, we investigate the clinical presentation and comorbidities of hypertensive crisis by evaluating the data collected between January and April 2009. We included 154 patients admitted with systolic and diastolic blood pressure of >179 mm Hg and >119 mm Hg (based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria) in the Department of Internal Medicine, Salmaniya Medical Complex, Kingdom of Bahrain. In the study population, 64.3% had hypertensive urgency (blood pressure elevation without end organ damage) and 35.7% had hypertensive emergency (blood pressure elevation with end organ damage). The mean age group was 45-65 years (56% of the study population) and more men were affected than women (100:54). Shortness of breath and neurological deficits had a strong statistical association with hypertensive emergency, and headache and blurring of vision had the same tendency toward hypertensive urgency. Diabetes mellitus was an independent risk factor for hypertensive crisis. Most of the studied patients were known hypertensive. Diabetes mellitus is powerful predictor for hypertensive crisis. Dyspnea and neurological deficits have significant statistical correlation with hypertensive emergencies.

  14. Targeting of beta 1 integrins impairs DNA repair for radiosensitization of head and neck cancer cells

    NARCIS (Netherlands)

    Dickreuter, E.; Eke, I.; Krause, M.; Borgmann, K.; van Vugt, M. A.; Cordes, N.

    2016-01-01

    beta 1 Integrin-mediated cell-extracellular matrix interactions allow cancer cell survival and confer therapy resistance. It was shown that inhibition of beta 1 integrins sensitizes cells to radiotherapy. Here, we examined the impact of beta 1 integrin targeting on the repair of radiation-induced

  15. An integrated miRNA functional screening and target validation method for organ morphogenesis

    OpenAIRE

    Rebustini, Ivan T.; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A.; Maas, Richard L.

    2016-01-01

    The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our ...

  16. Downregulation of Protein 4.1R impairs centrosome function,bipolar spindle organization and anaphase

    Energy Technology Data Exchange (ETDEWEB)

    Spence, Jeffrey R.; Go, Minjoung M.; Bahmanyar, S.; Barth,A.I.M.; Krauss, Sharon Wald

    2006-03-17

    Centrosomes nucleate and organize interphase MTs and areinstrumental in the assembly of the mitotic bipolar spindle. Here wereport that two members of the multifunctional protein 4.1 family havedistinct distributions at centrosomes. Protein 4.1R localizes to maturecentrioles whereas 4.1G is a component of the pericentriolar matrixsurrounding centrioles. To selectively probe 4.1R function, we used RNAinterference-mediated depletion of 4.1R without decreasing 4.1Gexpression. 4.1R downregulation reduces MT anchoring and organization atinterphase and impairs centrosome separation during prometaphase.Metaphase chromosomes fail to properly condense/align and spindleorganization is aberrant. Notably 4.1R depletion causes mislocalizationof its binding partner NuMA (Nuclear Mitotic Apparatus Protein),essential for spindle pole focusing, and disrupts ninein. Duringanaphase/telophase, 4.1R-depleted cells have lagging chromosomes andaberrant MT bridges. Our data provide functional evidence that 4.1R makescrucial contributions to centrosome integrity and to mitotic spindlestructure enabling mitosis and anaphase to proceed with the coordinatedprecision required to avoid pathological events.

  17. Impaired collagen synthesis in the rectum may be a molecular target in anastomotic leakage prophylaxis

    DEFF Research Database (Denmark)

    Buch, Anastasia S; Schjerling, Peter; Kjaer, Marie

    2017-01-01

    The underlying molecular mechanisms for anastomotic leakage (AL) after colorectal surgery are unknown and there are no therapeutics for AL prevention. Our aim was to correlate endogenous matrix metalloproteinase (MMP) activity, collagen concentration, and collagen/MMP/cytokine mRNA levels with an...... anatomic locations. By elucidating the factors responsible for the decreased collagen production we may identify specific molecular targets in AL prophylaxis....

  18. MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38.

    Directory of Open Access Journals (Sweden)

    Xue Liang

    Full Text Available Dendritic cells (DCs play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22 as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.

  19. Thymosin beta4 targeting impairs tumorigenic activity of colon cancer stem cells.

    Science.gov (United States)

    Ricci-Vitiani, Lucia; Mollinari, Cristiana; di Martino, Simona; Biffoni, Mauro; Pilozzi, Emanuela; Pagliuca, Alfredo; de Stefano, Maria Chiara; Circo, Rita; Merlo, Daniela; De Maria, Ruggero; Garaci, Enrico

    2010-11-01

    Thymosin β4 (Tβ4) is an actin-binding peptide overexpressed in several tumors, including colon carcinomas. The aim of this study was to investigate the role of Tβ4 in promoting the tumorigenic properties of colorectal cancer stem cells (CR-CSCs), which are responsible for tumor initiation and growth. We first found that CR-CSCs from different patients have higher Tβ4 levels than normal epithelial cells. Then, we used a lentiviral strategy to down-regulate Tβ4 expression in CR-CSCs and analyzed the effects of such modulation on proliferation, survival, and tumorigenic activity of CR-CSCs. Empty vector-transduced CR-CSCs were used as a control. Targeting of the Tβ4 produced CR-CSCs with a lower capacity to grow and migrate in culture and, interestingly, reduced tumor size and aggressiveness of CR-CSC-based xenografts in mice. Moreover, such loss in tumorigenic activity was accompanied by a significant increase of phosphatase and tensin homologue (PTEN) and a concomitant reduction of the integrin-linked kinase (ILK) expression, which resulted in a decreased activation of protein kinase B (Akt). Accordingly, exogenous expression of an active form of Akt rescued all the protumoral features lost after Tβ4 targeting in CR-CSCs. In conclusion, Tβ4 may have important implications for therapeutic intervention for treatment of human colon carcinoma.

  20. Overexpression of miR-19b Impairs Cardiac Development in Zebrafish by Targeting ctnnb1

    Directory of Open Access Journals (Sweden)

    Mengmeng Li

    2014-07-01

    Full Text Available Background: MicroRNAs are broadly accepted as crucial regulators of cardiovascular development, and dysregulation of their expression has been linked to cardiac disease. MicroRNA cluster miR-17-92 has been implicated in cardiac development and function, yet its defined mechanisms of action in this context are uncertain. Here, we focused on miR-19b, a key component of the miR-17-92 cluster proven to induce cardiomyocyte proliferation in vitro. We aimed to identify the biological significance of miR-19b in cardiac development and its underlying molecular mechanism of action in vivo. Methods: We micro-injected zebrafish embryos with different concentrations (0, 2, 4 and 8 μm of miR-19b mimics or a negative control, and assessed the embryo malformation rate, mortality rate, hatching rate and heart abnormalities at 72 hours post-fertilization (72 hpf. Results: We found that overexpression of miR-19b impacted left-right symmetry and cardiac development of zebrafish embryos, characterized by pericardial edema, slower heart rate and cardiac looping defects in a dose-dependent manner. Moreover, several important signaling molecules in the Wnt signaling pathway were abnormally expressed, suggesting that overexpression of miR-19b induces the inhibition of the Wnt signaling pathway by directly targeting ctnnb1. Interestingly, the deformed cardiac phenotype was partially rescued by treatment with the GSK3β inhibitor lithium chloride. Conclusion: Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1.

  1. Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various organs.

    Science.gov (United States)

    Zhu, Lianhua; Guo, Yanli; Wang, Luofu; Fan, Xiaozhou; Xiong, Xingyu; Fang, Kejing; Xu, Dan

    2017-09-29

    Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it's a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated. The mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P polypeptides can specifically enhance ultrasound imaging in CAIX-positive transplanted tumor tissues and could potentially be used in early diagnosis of a variety of solid tumors derived from various organs.

  2. The Navy’s Aerial Targets Program Management Organization and Recommend Improvements Thereto.

    Science.gov (United States)

    1980-06-01

    p5 LIST OF FIGURES 1. THE ORGANIZATION CHART OF THE OFFICE OF THE CHIEF OF NAVAL OPERATIONS---------------------- 9 2. THE STRUCTURE OF THE OFFICE OF...PROGRAM 20 5. THE ORGANIZATION CHART OF THE HEADQUARTERS NAVAL MATERIAL COMMAND ------------------------- 22 6. THE STRUCTURE OF THE DEPUTY CHIEF OF...NAVAL MATERIAL FOR ACQUISITION (MAT-08) -------------- 23 7. THE ORGANIZATION CHART OF THE NAVAL AIR SYSTEMS COMMAND FOR TARGETS

  3. Can hyperbaric oxygenation improve cognitive functioning in the organically impaired elderly?: a critical review.

    Science.gov (United States)

    Eisner, D A

    1975-01-01

    The present article reviews experimental investigation concerned with the effect of hyperbaric oxygenation upon cognitive functioning in the organically-impaired elderly. The conclusion of the Jacobs et al. studies was that hyperbaric oxygenation in cases of chronic organic brain damage (regardless of etiology) leads to improvement in cognitive functioning and general behavior on the ward. Goldfarb et al. (1972) found no evidence to support this conclusion. A critique of the above studies indicates several methodological weaknesses. First, there are serious reservations concerning the makeup of the samples employed in the Jacobs et al. (1969, 1971, 1972, 1973) investigations: it is highly uncertain that most of the Jacobs et al. subjects were suffering from moderate or severe chronic organic brain damage. One reason for the discrepancy between the Jacobs and Goldfarb studies is that the subjects in the later study were more deteriorated and perhaps not as amenable to hyperbaric oxygenation. Secondly, the Bender-Gestalt Test and Tien's Organic Integrity Test have not been validated in an elderly sample. The gain evidenced on the Stockton Geriatric Rating Scale (Jacobs et al., 1969, 1971, 1972) may have little practical significance, and since the data were pooled across groups, the so-called falloff effect could not have been measured. Third, and most significantly, the experimental designs employed in the Jacobs et al., the Goldfarb et al., and the Jacobs followup investigations have such serious shortcomings that the findings must be regarded as inconclusive. Such factors as experimenter attention, testing effects, and familiarity with the experimenter could account for the change in cognitive functioning. Further, in the case of the Jacobs et al. study, the ward personnel may have treated the control group differently after learning that they were expected to improve. Additionally, the subjects in the Jacobs et al. study (1969) themselves may have heard about

  4. Impairment of the organization of locomotor and exploratory behaviors in bile duct-ligated rats

    DEFF Research Database (Denmark)

    Leke, Renata; de Oliveira, Diogo L; Mussulini, Ben Hur M.

    2012-01-01

    Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to several problems, including motor impairment. Animal models of chronic liver disease have extensively investigated the mechanisms of this disease. Impairment of locomotor activity has been described in different ...

  5. Hypertensive Target Organ Damage and Longitudinal Changes in Brain Structure and Function: The Second Manifestations of Arterial Disease-Magnetic Resonance Study.

    Science.gov (United States)

    van der Veen, Pieternella H; Geerlings, Mirjam I; Visseren, Frank L J; Nathoe, Hendrik M; Mali, Willem P T M; van der Graaf, Yolanda; Muller, Majon

    2015-12-01

    Hypertension has been related to structural and functional brain changes. In high-risk populations, hypertensive target organ damage might better represent exposure to high blood pressure than the blood pressure measurement itself. We examined the association of hypertensive target organ damage with longitudinal changes in brain structure and function within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study. Renal function, albuminuria, and left ventricular hypertrophy on electrocardiography were measured in 663 patients with manifest arterial disease (mean age, 57±9 years; 81% men). Automated brain segmentation was used to quantify progression of global brain atrophy (change in brain parenchymal fraction) and progression of cerebral small vessel disease on 1.5T magnetic resonance imaging, and memory and executive functioning were assessed at baseline and after on average 3.9 years of follow-up. Regression analyses showed that an increasing number of signs of target organ damage was associated with more progression of global brain atrophy and more rapid decline in memory performance. Compared with no target organ damage, mean differences in change in brain parenchymal fraction (95% confidence interval) for 1 and ≥2 signs of organ damage were -0.12 (-0.30; 0.06) and -0.41 (-0.77; -0.05) % intracranial volume, and mean (95% confidence interval) differences in change in memory performance (z score) were -0.15 (-0.29; -0.00) and -0.27 (-0.54; -0.01). Results were independent of blood pressure, antihypertensive treatment, and other confounders. Hypertension target organ damage was not associated with progression of cerebral small vessel disease or change in executive functioning. Routinely assessed signs of hypertensive target organ damage, and in particular impaired renal function, could be used to identify patients at the highest risk of cognitive decline. © 2015 American Heart Association, Inc.

  6. Impaired Osteoblastogenesis in a Murine Model of Dominant Osteogenesis Imperfecta: A New Target for Osteogenesis Imperfecta Pharmacological Therapy

    Science.gov (United States)

    Gioia, Roberta; Panaroni, Cristina; Besio, Roberta; Palladini, Giovanni; Merlini, Giampaolo; Giansanti, Vincenzo; Scovassi, Ivana A.; Villani, Simona; Villa, Isabella; Villa, Anna; Vezzoni, Paolo; Tenni, Ruggero; Rossi, Antonio; Marini, Joan C.; Forlino, Antonella

    2012-01-01

    The molecular basis underlying the clinical phenotype in bone diseases is customarily associated with abnormal extracellular matrix structure and/or properties. More recently, cellular malfunction has been identified as a concomitant causative factor and increased attention has focused on stem cells differentiation. Classic osteogenesis imperfecta (OI) is a prototype for heritable bone dysplasias: it has dominant genetic transmission and is caused by mutations in the genes coding for collagen I, the most abundant protein in bone. Using the Brtl mouse, a well-characterized knockin model for moderately severe dominant OI, we demonstrated an impairment in the differentiation of bone marrow progenitor cells toward osteoblasts. In mutant mesenchymal stem cells (MSCs), the expression of early (Runx2 and Sp7) and late (Col1a1 and Ibsp) osteoblastic markers was significantly reduced with respect to wild type (WT). Conversely, mutant MSCs generated more colony-forming unit-adipocytes compared to WT, with more adipocytes per colony, and increased number and size of triglyceride drops per cell. Autophagy upregulation was also demonstrated in mutant adult MSCs differentiating toward osteogenic lineage as consequence of endoplasmic reticulum stress due to mutant collagen retention. Treatment of the Brtl mice with the proteasome inhibitor Bortezomib ameliorated both osteoblast differentiation in vitro and bone properties in vivo as demonstrated by colony-forming unit-osteoblasts assay and peripheral quantitative computed tomography analysis on long bones, respectively. This is the first report of impaired MSC differentiation to osteoblasts in OI, and it identifies a new potential target for the pharmacological treatment of the disorder. PMID:22511244

  7. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

    Directory of Open Access Journals (Sweden)

    Mario U Manto

    2015-03-01

    Full Text Available Autoantibodies to the smaller isoform of glutamate decarboxylase can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct glutamate decarboxylase autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal glutamate decarboxylase antibodies. We found that glutamate decarboxylase autoantibodies present in patients with stiff person syndrome (n = 7 and cerebellar ataxia (n = 15 recognized an epitope distinct from that recognized by glutamate decarboxylase autoantibodies present in patients with type 1 diabetes mellitus (n = 10 or limbic encephalitis (n = 4. We demonstrated that the administration of a monoclonal glutamate decarboxylase antibody representing this epitope specificity (1 disrupted in vitro the association of glutamate decarboxylase with γ-Aminobutyric acid containing synaptic vesicles, (2 depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect, (3 significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task, (4 markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm, and (5 induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of glutamate decarboxylase by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such glutamate decarboxylase antibodies could be envisioned.

  8. Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism.

    Science.gov (United States)

    de Souza Silva, Maria A; Lenz, Bernd; Rotter, Andrea; Biermann, Teresa; Peters, Oliver; Ramirez, Alfredo; Jessen, Frank; Maier, Wolfgang; Hüll, Michael; Schröder, Johannes; Frölich, Lutz; Teipel, Stefan; Gruber, Oliver; Kornhuber, Johannes; Huston, Joseph P; Müller, Christian P; Schäble, Sandra

    2013-09-10

    Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism.

  9. Impact of fungicide and insecticide use on non-target aquatic organisms in rice paddy fields

    Directory of Open Access Journals (Sweden)

    Alana Cristina Dorneles Wandscheer

    Full Text Available ABSTRACT: The intensive use of plant protection products in rice paddy fields ( Oryza sativa L. has caused concern about the environmental impact on communities of non-target organisms that are natural inhabitants in these agroecosystems. The purpose of this review is to analyze the data currently available in the literature about some important fungicides and insecticides (such as trifloxystrobin, tebuconazole, tricyclazole, lambda-cyhalothrin, and thiamethoxam, which are currently used to control pests and diseases in rice paddy fields, as well as their effects on the community of non-target aquatic organisms.

  10. Non-Governmental Organization (NGO Libraries for The Visually Impaired in Nigeria: Alternative Format Use and Perception of Information Services

    Directory of Open Access Journals (Sweden)

    Adetoro, 'Niran

    2015-03-01

    Full Text Available Nigeria's non-government organization (NGO libraries for the visually impaired has over the years been at the forefront of information services provision to persons with visual impairment. This study adopted a survey research design to investigate use of alternative formats and perceptions of information services to the visually impaired, focusing on two purposively chosen NGO libraries for the visually impaired in Nigeria. Using a complete enumeration approach, data were gathered from 180 users of the libraries through the use of a structured questionnaire with a reliability score (${\\alpha}=0.74$. Data from 112 (62.2% of the 180 administered copies of a questionnaire that were retrieved were analysed. The study found that Braille materials had a high level of utilization ($\\bar{x}=4.46$ and were the most frequently utilized (90.9%. Perception of information services by the visually impaired was positive while use of alternative formats was significantly and positively related to users' perception of information services (r = .041; p < 0.05. The study recommends improved transcription and investment in alternative formats and in e-resources. It also recommends collaborations to widen access as well as constant evaluation of services.

  11. Delineation of target volumes and organs at risk in adjuvant radiotherapy of early breast cancer

    DEFF Research Database (Denmark)

    Holck Nielsen, Mette; Berg, Martin; Pedersen, Anders N

    2013-01-01

    During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus...... on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required....

  12. Self-aligned optical couplings by self-organized waveguides toward luminescent targets in organic/inorganic hybrid materials.

    Science.gov (United States)

    Yoshimura, Tetsuzo; Iida, Makoto; Nawata, Hideyuki

    2014-06-15

    Self-organization of optical waveguides is observed between two opposed optical fibers placed in a photosensitive organic/inorganic hybrid material, Sunconnect. A luminescent target containing coumarin 481 was deposited onto the edge of one of the two fibers at the core. When a 448-nm write beam was introduced from the other fiber, the write beam and the luminescence from the photoexcited target increased the refractive index of Sunconnect to induce self-focusing. Traces of waveguides were seen to grow from the cores of both fibers and merged into a single self-aligned optical coupling between the fibers. This optical solder functionality enabled increases in both coupling efficiency and tolerance to lateral misalignment of the fibers.

  13. Target organ damage among hypertensive adults in rural Nigeria: a cross-sectional study

    NARCIS (Netherlands)

    Nelissen, Heleen E.; Hendriks, Marleen E.; Wit, Ferdinand W. N. M.; Bolarinwa, Oladimeji A.; Osagbemi, Gordon K.; Bindraban, Navin R.; Lange, Joep M. A.; Akande, Tanimola M.; Schultsz, Constance; Brewster, Lizzy M.

    2014-01-01

    To study the prevalence of target organ damage (TOD) in hypertensive adults in a general population in rural Nigeria, to assess determinants of TOD and the contribution of TOD screening to assess eligibility for antihypertensive treatment. All adults diagnosed with hypertension (n=387) and a random

  14. Comparison of the Absorbed Dose of Target Organs between Conventional and Digital Panoramic Radiography

    Directory of Open Access Journals (Sweden)

    Zohre Reyhani

    2016-09-01

    Full Text Available The purpose of this study was to measure and compare target organ’s exposure by direct digital and conventional panoramic radiography. Dose measurements were carried out on a RANDO phantom, which TLDs were placed into 5 target area: thyroid gland, left and right submandibular and parotid salivary glands. Panoramic radiographs were taken with two conventional (CRANEX Tome, Soredex, Tusula Finland and direct digital devices (CRANEX D, Soredex, Tusula Finland.In total, the phantom was irradiated 30 times in the two systems. The TLDs were then coded and analyzed. T-test of statistical analysis was used to find the correlation. We found statistically significant reduction in absorbed dose of target organs in digital panoramic radiography(P<0.01. The highest absorbed dose was for submandibular gland and the lowest was for thyroid gland. We concluded that can reduce absorbed dose in vital organs.

  15. ZFNGenome: A comprehensive resource for locating zinc finger nuclease target sites in model organisms

    Directory of Open Access Journals (Sweden)

    Voytas Daniel F

    2011-01-01

    Full Text Available Abstract Background Zinc Finger Nucleases (ZFNs have tremendous potential as tools to facilitate genomic modifications, such as precise gene knockouts or gene replacements by homologous recombination. ZFNs can be used to advance both basic research and clinical applications, including gene therapy. Recently, the ability to engineer ZFNs that target any desired genomic DNA sequence with high fidelity has improved significantly with the introduction of rapid, robust, and publicly available techniques for ZFN design such as the Oligomerized Pool ENgineering (OPEN method. The motivation for this study is to make resources for genome modifications using OPEN-generated ZFNs more accessible to researchers by creating a user-friendly interface that identifies and provides quality scores for all potential ZFN target sites in the complete genomes of several model organisms. Description ZFNGenome is a GBrowse-based tool for identifying and visualizing potential target sites for OPEN-generated ZFNs. ZFNGenome currently includes a total of more than 11.6 million potential ZFN target sites, mapped within the fully sequenced genomes of seven model organisms; S. cerevisiae, C. reinhardtii, A. thaliana, D. melanogaster, D. rerio, C. elegans, and H. sapiens and can be visualized within the flexible GBrowse environment. Additional model organisms will be included in future updates. ZFNGenome provides information about each potential ZFN target site, including its chromosomal location and position relative to transcription initiation site(s. Users can query ZFNGenome using several different criteria (e.g., gene ID, transcript ID, target site sequence. Tracks in ZFNGenome also provide "uniqueness" and ZiFOpT (Zinc Finger OPEN Targeter "confidence" scores that estimate the likelihood that a chosen ZFN target site will function in vivo. ZFNGenome is dynamically linked to ZiFDB, allowing users access to all available information about zinc finger reagents, such as the

  16. Review of the effects of manufactured nanoparticles on mammalian target organs.

    Science.gov (United States)

    Wu, Tianshu; Tang, Meng

    2018-01-01

    Nanotechnology had matured significantly during the last two decades as it has transitioned from bench top science to applied technology. Even though the issue of safety of nanotechnology has been raised nearly one decade ago, the rapid progress in development and use of nanomaterials has not yet been matched by toxicological investigations. Many recent studies have simply outlined the toxic effects of nanoparticles (NPs), but few have systematically addressed their potentially adverse biological effects on target organs. Some animal models have shown that NPs could be accumulated in various organs. These accumulations can access the vasculature and target other organs, resulting in a potential health risks. After the brief description of current knowledge on the wide applications of several common NPs, their applications and the toxicokinetics, this review focused on effects of NPs on organ functions and mammal health after acute or chronic exposure, and potential mechanisms of action. Due to their physical properties, the liver, kidneys and lung are the main target organs of NPs. Most of NPs show slight toxicity when exposed to animals, while certain toxic effects like oxidative stress generation, inflammation and DNA damage are commonly observed. The severity of NPs toxicity is dependent upon several factors, including exposure dose and administration, NPs chemistry, size, shape, agglomeration state, and electromagnetic properties, which could provide useful information necessary to control the toxicity of NPs. Finally, the safety evaluation of nanotoxicity was addressed. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Organ Impairment—Drug–Drug Interaction Database: A Tool for Evaluating the Impact of Renal or Hepatic Impairment and Pharmacologic Inhibition on the Systemic Exposure of Drugs

    Science.gov (United States)

    Yeung, CK; Yoshida, K; Kusama, M; Zhang, H; Ragueneau-Majlessi, I; Argon, S; Li, L; Chang, P; Le, CD; Zhao, P; Zhang, L; Sugiyama, Y; Huang, S-M

    2015-01-01

    The organ impairment and drug–drug interaction (OI-DDI) database is the first rigorously assembled database of pharmacokinetic drug exposure data from publicly available renal and hepatic impairment studies presented together with the maximum change in drug exposure from drug interaction inhibition studies. The database was used to conduct a systematic comparison of the effect of renal/hepatic impairment and pharmacologic inhibition on drug exposure. Additional applications are feasible with the public availability of this database. PMID:26380158

  18. The World Health Organization's global target for reducing childhood stunting by 2025: rationale and proposed actions.

    Science.gov (United States)

    de Onis, Mercedes; Dewey, Kathryn G; Borghi, Elaine; Onyango, Adelheid W; Blössner, Monika; Daelmans, Bernadette; Piwoz, Ellen; Branca, Francesco

    2013-09-01

    In 2012, the World Health Organization adopted a resolution on maternal, infant and young child nutrition that included a global target to reduce by 40% the number of stunted under-five children by 2025. The target was based on analyses of time series data from 148 countries and national success stories in tackling undernutrition. The global target translates to a 3.9% reduction per year and implies decreasing the number of stunted children from 171 million in 2010 to about 100 million in 2025. However, at current rates of progress, there will be 127 million stunted children by 2025, that is, 27 million more than the target or a reduction of only 26%. The translation of the global target into national targets needs to consider nutrition profiles, risk factor trends, demographic changes, experience with developing and implementing nutrition policies, and health system development. This paper presents a methodology to set individual country targets, without precluding the use of others. Any method applied will be influenced by country-specific population growth rates. A key question is what countries should do to meet the target. Nutrition interventions alone are almost certainly insufficient, hence the importance of ongoing efforts to foster nutrition-sensitive development and encourage development of evidence-based, multisectoral plans to address stunting at national scale, combining direct nutrition interventions with strategies concerning health, family planning, water and sanitation, and other factors that affect the risk of stunting. In addition, an accountability framework needs to be developed and surveillance systems strengthened to monitor the achievement of commitments and targets. © 2013 John Wiley & Sons Ltd.

  19. Identification of relevant non-target organisms exposed to weevil-resistant Bt sweetpotato in Uganda.

    Science.gov (United States)

    Rukarwa, R J; Mukasa, S B; Odongo, B; Ssemakula, G; Ghislain, M

    2014-06-01

    Assessment of the impact of transgenic crops on non-target organisms (NTO) is a prerequisite to their release into the target environment for commercial use. Transgenic sweetpotato varieties expressing Cry proteins (Bt sweetpotato) are under development to provide effective protection against sweetpotato weevils (Coleoptera) which cause severe economic losses in sub-Saharan Africa. Like any other pest control technologies, genetically engineered crops expressing insecticidal proteins need to be evaluated to assess potential negative effects on non-target organisms that provide important services to the ecosystem. Beneficial arthropods in sweetpotato production systems can include pollinators, decomposers, and predators and parasitoids of the target insect pest(s). Non-target arthropod species commonly found in sweetpotato fields that are related taxonomically to the target pests were identified through expert consultation and literature review in Uganda where Bt sweetpotato is expected to be initially evaluated. Results indicate the presence of few relevant non-target Coleopterans that could be affected by Coleopteran Bt sweetpotato varieties: ground, rove and ladybird beetles. These insects are important predators in sweetpotato fields. Additionally, honeybee (hymenoptera) is the main pollinator of sweetpotato and used for honey production. Numerous studies have shown that honeybees are unaffected by the Cry proteins currently deployed which are homologous to those of the weevil-resistant Bt sweetpotato. However, because of their feeding behaviour, Bt sweetpotato represents an extremely low hazard due to negligible exposure. Hence, we conclude that there is good evidence from literature and expert opinion that relevant NTOs in sweetpotato fields are unlikely to be affected by the introduction of Bt sweetpotato in Uganda.

  20. Penentuan Secara Imunopatologi Organ Target Virus Flu Burung Menggunakan Streptavidin Biotin (DETERMINATION OF TARGET ORGANS OF AVIAN INFLUENZA VIRUS USING IMMUNOPATHOLOGICAL IMMUNOHISTOCHEMISTRY STREPTAVIDIN-BIOTIN

    Directory of Open Access Journals (Sweden)

    Niken Yunita

    2018-01-01

    Full Text Available Avian influenza is a viral disease in poultry caused by avian influenza virus (AIV subtype H5N1 with varying clinical signs are often similar to the clinical signs of other viral infections, such as Newcastle disease virus (NDV. The mechanism of disease pathogenesis to express clinical signs tightly correlated to the determination of the target organ seen from AIV H5N1 antigens distribution in organs, such as respiratory tract, brain and gastrointestinal tract. Immunopathological immunohistochemistry streptavidin-biotin (IHC SB is a method for sensitive and accurate in detecting antigens of AIV on the tissues. In the present study, it was determined whether in laying hens with clinical signs of torticollis and curled toe paralysis, and pathologic anatomic lesions in the form of petechial and foci necrotic hemorrhages tested with immunopathological IHC SB is positive AIV H5N1 infection. IHC SB study results showed that the AIV H5N1 antigen were found in tissues of the lung, brain, duodenum and proventriculus. Based on these results, we can conclude that the IHC SB is a method that is highly sensitive and accurate to detect H5N1 antigens and its distribution in the host.

  1. Targeting organic anion transporter 3 with probenecid as a novel anti-influenza a virus strategy.

    Science.gov (United States)

    Perwitasari, Olivia; Yan, Xiuzhen; Johnson, Scott; White, Caleb; Brooks, Paula; Tompkins, S Mark; Tripp, Ralph A

    2013-01-01

    Influenza A virus infection is a major global health concern causing significant mortality, morbidity, and economic loss. Antiviral chemotherapeutics that target influenza A virus are available; however, rapid emergence of drug-resistant strains has been reported. Consequently, there is a burgeoning need to identify novel anti-influenza A drugs, particularly those that target host gene products required for virus replication, to reduce the likelihood of drug resistance. In this study, a small interfering RNA (siRNA) screen was performed to identify host druggable gene targets for anti-influenza A virus therapy. The host organic anion transporter-3 gene (OAT3), a member of the SLC22 family of transporters, was validated as being required to support influenza A virus replication. Probenecid, a prototypical uricosuric agent and chemical inhibitor of organic anion transporters known to target OAT3, was shown to be effective in limiting influenza A virus infection in vitro (50% inhibitory concentration [IC(50)] of 5.0 × 10(-5) to 5.0 × 10(-4) μM; P Probenecid is widely used for treatment of gout and related hyperuricemic disorders, has been extensively studied for pharmacokinetics and safety, and represents an excellent candidate for drug repositioning as a novel anti-influenza A chemotherapeutic.

  2. Target Organ Metabolism, Toxicity, and Mechanisms of Trichloroethylene and Perchloroethylene: Key Similarities, Differences, and Data Gaps.

    Science.gov (United States)

    Cichocki, Joseph A; Guyton, Kathryn Z; Guha, Neela; Chiu, Weihsueh A; Rusyn, Ivan; Lash, Lawrence H

    2016-10-01

    Trichloroethylene (TCE) and perchloroethylene or tetrachloroethylene (PCE) are high-production volume chemicals with numerous industrial applications. As a consequence of their widespread use, these chemicals are ubiquitous environmental contaminants to which the general population is commonly exposed. It is widely assumed that TCE and PCE are toxicologically similar; both are simple olefins with three (TCE) or four (PCE) chlorines. Nonetheless, despite decades of research on the adverse health effects of TCE or PCE, few studies have directly compared these two toxicants. Although the metabolic pathways are qualitatively similar, quantitative differences in the flux and yield of metabolites exist. Recent human health assessments have uncovered some overlap in target organs that are affected by exposure to TCE or PCE, and divergent species- and sex-specificity with regard to cancer and noncancer hazards. The objective of this minireview is to highlight key similarities, differences, and data gaps in target organ metabolism and mechanism of toxicity. The main anticipated outcome of this review is to encourage research to 1) directly compare the responses to TCE and PCE using more sensitive biochemical techniques and robust statistical comparisons; 2) more closely examine interindividual variability in the relationship between toxicokinetics and toxicodynamics for TCE and PCE; 3) elucidate the effect of coexposure to these two toxicants; and 4) explore new mechanisms for target organ toxicity associated with TCE and/or PCE exposure. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Specific Organ Targeted Vestibular Physiotherapy: The Pivot in the Contemporary Management of Vertigo and Imbalance.

    Science.gov (United States)

    Biswas, Anirban; Barui, Bibhas

    2017-12-01

    Advancements in our understanding of vestibular physiology and how it is changes in different diseases have established that of the three therapeutic approaches to treat disorders of the vestibular system viz. pharmacotherapy, surgery and physical therapy, it is the later i.e., physical therapy which is the most efficacious modality in the management of balance disorders. The futility of vestibular sedatives in the correction of vestibular disorders and in the restoration of balance and the very limited role of surgery has now been recognised. Advancements in vestibulometry now enable us to localise any lesion in the vestibular system with utmost precision and also determine the exact cause of the balance disorder. The site of lesion and the specific organ that is defective can now be very precisely identified. Treatment modalities especially that for physical therapy hence have to be organ specific, and if possible, also disease specific. The study aims at evaluating the efficacy of physiotherapy in the management of balance disorders and also assesses the efficacy of organ targeted physical therapy, a new concept in restoring balance after vestibulometry has identified the offending organ. The study was conducted in the specialised physical therapy unit for balance and gait disorder patients which is a part of Vertigo and Deafness Clinic in Kolkata, India. Special instruments for physical therapy devised by the first author were used for stimulation of specific sense organs in the vestibular labyrinth that were found to be defective in vestibulometry. Specially made Virtual reality programs were used in patients suffering from psychogenic balance disorders. The pre and post therapy status was evaluated by different standard scales to assess balance and dizziness. Very promising results were obtained. Organ targeted physiotherapy where defective sense organs were specifically stimulated showed remarkable improvement in different measures. Virtual reality exercises

  4. 5-HT1A receptor blockade targeting the basolateral amygdala improved stress-induced impairment of memory consolidation and retrieval in rats.

    Science.gov (United States)

    Sardari, M; Rezayof, A; Zarrindast, M-R

    2015-08-06

    The aim of the present study was to investigate the possible role of basolateral amygdala (BLA) 5-HT1A receptors in memory formation under stress. We also examined whether the blockade of these receptors is involved in stress-induced state-dependent memory. Adult male Wistar rats received cannula implants that bilaterally targeted the BLA. Long-term memory was examined using the step-through type of passive avoidance task. Behavioral stress was evoked by exposure to an elevated platform (EP) for 10, 20 and 30min. Post-training exposure to acute stress (30min) impaired the memory consolidation. In addition, pre-test exposure to acute stress-(20 and 30min) induced the impairment of memory retrieval. Interestingly, the memory impairment induced by post-training exposure to stress was restored in the animals that received 20- or 30-min pre-test stress exposure, suggesting stress-induced state-dependent memory retrieval. Post-training BLA-targeted injection of a selective 5-HT1A receptor antagonist, (S)-WAY-100135 (2μg/rat), prevented the impairing effect of stress on memory consolidation. Pre-test injection of the same doses of (S)-WAY-100135 that was targeted to the BLA also reversed stress-induced memory retrieval impairment. It should be considered that post-training or pre-test BLA-targeted injection of (S)-WAY-100135 (0.5-2μg/rat) by itself had no effect on the memory formation. Moreover, pre-test injection of (S)-WAY-100135 (2μg/rat) that targeted the BLA inhibited the stress-induced state-dependent memory retrieval. Taken together, our findings suggest that post-training or pre-test exposure to acute stress induced the impairment of memory consolidation, retrieval and state-dependent learning. The BLA 5-HT1A receptors have a critical role in learning and memory under stress. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. SCF(SAP) controls organ size by targeting PPD proteins for degradation in Arabidopsis thaliana.

    Science.gov (United States)

    Wang, Zhibiao; Li, Na; Jiang, Shan; Gonzalez, Nathalie; Huang, Xiahe; Wang, Yingchun; Inzé, Dirk; Li, Yunhai

    2016-04-06

    Control of organ size by cell proliferation and growth is a fundamental process, but the mechanisms that determine the final size of organs are largely elusive in plants. We have previously revealed that the ubiquitin receptor DA1 regulates organ size by repressing cell proliferation in Arabidopsis. Here we report that a mutant allele of STERILE APETALA (SAP) suppresses the da1-1 mutant phenotype. We show that SAP is an F-box protein that forms part of a SKP1/Cullin/F-box E3 ubiquitin ligase complex and controls organ size by promoting the proliferation of meristemoid cells. Genetic analyses suggest that SAP may act in the same pathway with PEAPOD1 and PEAPOD2, which are negative regulators of meristemoid proliferation, to control organ size, but does so independently of DA1. Further results reveal that SAP physically associates with PEAPOD1 and PEAPOD2, and targets them for degradation. These findings define a molecular mechanism by which SAP and PEAPOD control organ size.

  6. Transcription Factors Expressed in Lateral Organ Boundaries: Identification of Downstream Targets

    Energy Technology Data Exchange (ETDEWEB)

    Springer, Patricia S

    2010-07-12

    The processes of lateral organ initiation and patterning are central to the generation of mature plant form. Characterization of the molecular mechanisms underlying these processes is essential to our understanding of plant development. Communication between the shoot apical meristem and initiating organ primordia is important both for functioning of the meristem and for proper organ patterning, and very little is known about this process. In particular, the boundary between meristem and leaf is emerging as a critical region that is important for SAM maintenance and regulation of organogenesis. The goal of this project was to characterize three boundary-expressed genes that encode predicted transcription factors. Specifically, we have studied LATERAL ORGAN BOUNDARIES (LOB), LATERAL ORGAN FUSION1 (LOF1), and LATERAL ORGAN FUSION2 (LOF2). LOB encodes the founding member of the LOB-DOMAIN (LBD) plant-specific DNA binding transcription factor family and LOF1 and LOF2 encode paralogous MYB-domain transcription factors. We characterized the genetic relationship between these three genes and other boundary and meristem genes. We also used an ectopic inducible expression system to identify direct targets of LOB.

  7. High-sensitivity C-reactive protein predicts target organ damage in Chinese patients with metabolic syndrome

    DEFF Research Database (Denmark)

    Zhao, Zhigang; Nie, Hai; He, Hongbo

    2007-01-01

    with metabolic syndrome. A total of 1082 consecutive patients of Chinese origin were screened for the presence of metabolic syndrome according to the National Cholesterol Education Program's Adult Treatment Panel III. High-sensitivity C-reactive protein and target organ damage, including cardiac hypertrophy......, carotid intima-media thickness, and renal impairment, were investigated. The median (25th and 75th percentiles) of high-sensitivity C-reactive protein in 619 patients with metabolic syndrome was 2.42 mg/L (0.75 and 3.66 mg/L) compared with 1.13 mg/L (0.51 and 2.46 mg/L) among 463 control subjects (P ...). There was a progressive increase in high-sensitivity C-reactive protein level with the number of components of the metabolic syndrome. Stratification of patients with metabolic syndrome into 3 groups according to their high-sensitivity C-reactive protein concentrations (3.0 mg/L) showed that the subjects...

  8. Enumerating metabolic pathways for the production of heterologous target chemicals in chassis organisms

    Directory of Open Access Journals (Sweden)

    Carbonell Pablo

    2012-02-01

    Full Text Available Abstract Background We consider the possibility of engineering metabolic pathways in a chassis organism in order to synthesize novel target compounds that are heterologous to the chassis. For this purpose, we model metabolic networks through hypergraphs where reactions are represented by hyperarcs. Each hyperarc represents an enzyme-catalyzed reaction that transforms set of substrates compounds into product compounds. We follow a retrosynthetic approach in order to search in the metabolic space (hypergraphs for pathways (hyperpaths linking the target compounds to a source set of compounds. Results To select the best pathways to engineer, we have developed an objective function that computes the cost of inserting a heterologous pathway in a given chassis organism. In order to find minimum-cost pathways, we propose in this paper two methods based on steady state analysis and network topology that are to the best of our knowledge, the first to enumerate all possible heterologous pathways linking a target compounds to a source set of compounds. In the context of metabolic engineering, the source set is composed of all naturally produced chassis compounds (endogenuous chassis metabolites and the target set can be any compound of the chemical space. We also provide an algorithm for identifying precursors which can be supplied to the growth media in order to increase the number of ways to synthesize specific target compounds. Conclusions We find the topological approach to be faster by several orders of magnitude than the steady state approach. Yet both methods are generally scalable in time with the number of pathways in the metabolic network. Therefore this work provides a powerful tool for pathway enumeration with direct application to biosynthetic pathway design.

  9. Inhibition of serotonin receptor type 1 in acute myeloid leukemia impairs leukemia stem cell functionality: a promising novel therapeutic target.

    Science.gov (United States)

    Etxabe, A; Lara-Castillo, M C; Cornet-Masana, J M; Banús-Mulet, A; Nomdedeu, M; Torrente, M A; Pratcorona, M; Díaz-Beyá, M; Esteve, J; Risueño, R M

    2017-11-01

    Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous neoplasia with poor outcome, organized as a hierarchy initiated and maintained by a sub-population with differentiation and self-renewal capacities called leukemia stem cells (LSCs). Although currently used chemotherapy is capable of initially reducing the tumor burden producing a complete remission, most patients will ultimately relapse and will succumb to their disease. As such, new therapeutic strategies are needed. AML cells differentially expressed serotonin receptor type 1 (HTR1) compared with healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome. Inhibition of HTR1s activated the apoptosis program, induced differentiation and reduced the clonogenic capacity, while minimal effect was observed on healthy blood cells. In vivo regeneration capacity of primary AML samples was disrupted upon inhibition of HTR1. The self-renewal capacity remaining in AML cells upon in vivo treatment was severely reduced as demonstrated by serial transplantation. Thus, treatment with HTR1 antagonists showed antileukemia effect, especially anti-LSC activity while sparing healthy blood cells. Our results highlight the importance of HTR1 in leukemogenesis and LSC survival and identify this receptor family as a new target for therapy in AML with prognostic value.

  10. The postnatal growth of ICRP target organs in reference humans: Spleen and liver

    International Nuclear Information System (INIS)

    Walker, J.T.

    1989-01-01

    Attempts to improve radiation dose estimates to infants and children are hampered because of the lack of mathematical models that describe the age variation in anatomical and physiological parameters. Specifically, for one anatomical parameter, organ size, there are no growth models available to the health physics community. In this paper, an empirical mathematical model is introduced for estimating age-specific masses of two ICRP target organs: the spleen and liver. That model, the Power Logistic Additive (PLA) growth model, is fitted to ICRP 23 organ growth data to determine five growth parameters. This model assumes that organs grow under the influence of two main processes: a primary (power function) and a sexual maturation (logistic function) process, which are additive from birth to adulthood. The results show that the model describes the ICRP growth data quite well. Growth parameters and tables listing the predicted masses and mass velocities as a function of age for each organ are provided for application in the ICRP modeling system

  11. Butenolide inhibits marine fouling by altering the primary metabolism of three target organisms

    KAUST Repository

    Zhang, Yifan

    2012-06-15

    Butenolide is a very promising antifouling compound that inhibits ship hull fouling by a variety of marine organisms, but its antifouling mechanism was previously unknown. Here we report the first study of butenolides molecular targets in three representative fouling organisms. In the barnacle Balanus (=Amphibalanus) amphitrite, butenolide bound to acetyl-CoA acetyltransferase 1 (ACAT1), which is involved in ketone body metabolism. Both the substrate and the product of ACAT1 increased larval settlement under butenolide treatment, suggesting its functional involvement. In the bryozoan Bugula neritina, butenolide bound to very long chain acyl-CoA dehydrogenase (ACADVL), actin, and glutathione S-transferases (GSTs). ACADVL is the first enzyme in the very long chain fatty acid β-oxidation pathway. The inhibition of this primary pathway for energy production in larvae by butenolide was supported by the finding that alternative energy sources (acetoacetate and pyruvate) increased larval attachment under butenolide treatment. In marine bacterium Vibrio sp. UST020129-010, butenolide bound to succinyl-CoA synthetase β subunit (SCSβ) and inhibited bacterial growth. ACAT1, ACADVL, and SCSβ are all involved in primary metabolism for energy production. These findings suggest that butenolide inhibits fouling by influencing the primary metabolism of target organisms. © 2012 American Chemical Society.

  12. Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

    Directory of Open Access Journals (Sweden)

    Chen Yu-Jen

    2009-12-01

    Full Text Available Abstract The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT, a new image-guided intensity modulated radiotherapy (IMRT, delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy.

  13. Biosafety research for non-target organism risk assessment of RNAi-based GE plants

    Science.gov (United States)

    Roberts, Andrew F.; Devos, Yann; Lemgo, Godwin N. Y.; Zhou, Xuguo

    2015-01-01

    RNA interference, or RNAi, refers to a set of biological processes that make use of conserved cellular machinery to silence genes. Although there are several variations in the source and mechanism, they are all triggered by double stranded RNA (dsRNA) which is processed by a protein complex into small, single stranded RNA, referred to as small interfering RNAs (siRNA) with complementarity to sequences in genes targeted for silencing. The use of the RNAi mechanism to develop new traits in plants has fueled a discussion about the environmental safety of the technology for these applications, and this was the subject of a symposium session at the 13th ISBGMO in Cape Town, South Africa. This paper continues that discussion by proposing research areas that may be beneficial for future environmental risk assessments of RNAi-based genetically modified plants, with a particular focus on non-target organism assessment. PMID:26594220

  14. Temporal cytokine expression and the target organ attributes unravel novel aspects of autoimmune arthritis.

    Science.gov (United States)

    Astry, Brian; Venkatesha, Shivaprasad H; Moudgil, Kamal D

    2013-11-01

    Susceptibility to autoimmunity is determined by multiple factors. Defining the contribution of the quantitative versus qualitative aspects of antigen-directed immune responses as well as the factors influencing target organ susceptibility is vital to advancing the understanding of the pathogenesis of autoimmunity. In a series of studies, we have addressed these issues using the adjuvant-induced arthritis (AA) model of human rheumatoid arthritis (RA). Lewis rats are susceptible to AA following immunization with heat-killed Mycobacterium tuberculosis H37Ra, whereas Wistar-Kyoto (WKY) rats of the same MHC (major histocompatibility complex) haplotype are resistant. Comparative studies on these and other susceptible/resistant rodent strains have offered interesting insights into differential cytokine responses in the face of comparable T cell proliferative response to the disease relevant antigens. Study of the cytokine kinetics have also permitted validation of the disease-protective versus disease-aggravating effects of specific cytokines by treatment of rats/mice with those cytokines at different phases of the disease. In regard to the target organ attributes, the migration of arthritogenic leukocytes into the joints; the expression of mediators of inflammation, angiogenesis, and tissue damage; the role of vascular permeability; and the characteristics of vascular endothelial cells have been examined. Further, various inhibitors of angiogenesis are effective in suppressing arthritis. Taken together, the differential cytokine responses and unique attributes of the target organ have revealed novel aspects of disease susceptibility and joint damage in AA. The translation of this basic research in animal models to RA patients would not only advance our understanding of the disease process, but also offer novel avenues for immunomodulation of this disease.

  15. Expanded target-chemical analysis reveals extensive mixed-organic-contaminant exposure in USA streams

    Science.gov (United States)

    Bradley, Paul M.; Journey, Celeste A.; Romanok, Kristin; Barber, Larry B.; Buxton, Herbert T.; Foreman, William; Furlong, Edward T.; Glassmeyer, Susan T.; Hladik, Michelle L.; Iwanowicz, Luke R.; Jones, Daniel K.; Kolpin, Dana W.; Kuivila, Kathryn M.; Loftin, Keith A.; Mills, Marc A.; Meyer, Michael T.; Orlando, James L.; Reilly, Timothy J.; Smalling, Kelly L.; Villeneuve, Daniel L.

    2017-01-01

    Surface water from 38 streams nationwide was assessed using 14 target-organic methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-organics included eight pesticides (desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT, glyphosate) and two pharmaceuticals (caffeine, metformin) with detection frequencies ranging 66–84% of all sites. Detected contaminant concentrations varied from less than 1 ng L–1 to greater than 10 μg L–1, with 77 and 278 having median detected concentrations greater than 100 ng L–1 and 10 ng L–1, respectively. Cumulative detections and concentrations ranged 4–161 compounds (median 70) and 8.5–102 847 ng L–1, respectively, and correlated significantly with wastewater discharge, watershed development, and toxic release inventory metrics. Log10 concentrations of widely monitored HHCB, triclosan, and carbamazepine explained 71–82% of the variability in the total number of compounds detected (linear regression; p-values: environment application (pesticides), designed-bioactive organics (median 41 per site at μg L–1 cumulative concentrations) in developed watersheds present aquatic health concerns, given their acknowledged potential for sublethal effects to sensitive species and lifecycle stages at low ng L–1.

  16. STRESS IN THE AIR: INHALED POLLUTANTS AND MULTI-ORGAN IMPAIRMENT

    Science.gov (United States)

    Air pollution has been blamed for nearly 7 million premature deaths worldwide. For decades, the research on how air pollution impacts human health has centered on cardiopulmonary consequences. However, more recently it is clearly evident that air pollution affects every organ in ...

  17. SFACTOR: a computer code for calculating dose equivalent to a target organ per microcurie-day residence of a radionuclide in a source organ

    International Nuclear Information System (INIS)

    Dunning, D.E. Jr.; Pleasant, J.C.; Killough, G.G.

    1977-11-01

    A computer code SFACTOR was developed to estimate the average dose equivalent S (rem/μCi-day) to each of a specified list of target organs per microcurie-day residence of a radionuclide in source organs in man. Source and target organs of interest are specified in the input data stream, along with the nuclear decay information. The SFACTOR code computes components of the dose equivalent rate from each type of decay present for a particular radionuclide, including alpha, electron, and gamma radiation. For those transuranic isotopes which also decay by spontaneous fission, components of S from the resulting fission fragments, neutrons, betas, and gammas are included in the tabulation. Tabulations of all components of S are provided for an array of 22 source organs and 24 target organs for 52 radionuclides in an adult

  18. Association of Morning Hypertension Subtype With Vascular Target Organ Damage and Central Hemodynamics.

    Science.gov (United States)

    Oh, Jaewon; Lee, Chan Joo; Kim, In-Cheol; Lee, Sang-Hak; Kang, Seok-Min; Choi, Donghoon; Park, Sungha; Kario, Kazuomi

    2017-02-14

    A recent study reported that morning hypertension is associated with poor cardiovascular outcomes in hypertensive patients. However, it is unclear whether morning hypertension associated with sustained nocturnal hypertension and that associated with morning blood pressure (BP) surge differ in terms of their effects on cardiovascular target organ damage and clinical outcomes. The present study aimed to determine the association of morning hypertension with/without nocturnal hypertension with vascular target organ damage and central hemodynamics in patients at high risk for cardiovascular disease. Ambulatory BP monitoring was performed and central BP was measured in 1070 consecutive patients with high cardiovascular risk. We grouped morning hypertension into the following 3 subtypes: (I) morning normotension; (II) morning hypertension without nocturnal hypertension; and (III) morning hypertension with nocturnal hypertension. Morning hypertension was noted in 469 (43.8%) patients and morning hypertension with nocturnal hypertension was noted in 374 (34.9%) patients. The central systolic/diastolic BP and carotid to femoral pulse wave velocity were significantly higher in the subtype III group than in the subtype I and II groups (all P Morning hypertension, especially that associated with nocturnal hypertension, is related to high central BP and increased arterial stiffness. Further studies on whether morning hypertension with or without nocturnal hypertension is related to clinical outcomes should be performed. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02003781. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  19. Assessment of Total Risk on Non-Target Organisms in Fungicide Application for Agricultural Sustainability

    Directory of Open Access Journals (Sweden)

    Ali Musa Bozdogan

    2014-02-01

    Full Text Available In Turkey, in 2010, the amount of pesticide (active ingredient; a.i. used in agriculture was about 23,000 metric tons, of which approximately 32% was fungicides. In 2012, 14 a.i. were used for fungus control in wheat cultivation areas in Adana province, Turkey. These a.i. were: azoxystrobin, carbendazim, difenoconazole, epoxiconazole, fluquinconazole, prochloraz, propiconazole, prothioconazole, pyraclostrobin, spiroxamine, tebuconazole, thiophanate-methyl, triadimenol, and trifloxystrobin. In this study, the potential risk of a.i. on non-target organisms in fungicide application of wheat cultivation was assessed by The Pesticide Occupational and Environmental Risk (POCER indicators. In this study, the highest human health risk was for fluquinconazole (Exceedence Factor (EF 1.798 for human health, whereas the fungicide with the highest environmental risk was propiconazole (EF 2.000 for the environment. For non-target organisms, the highest potential risk was determined for propiconazole when applied at 0.1250 kg a.i. ha-1 (EF 2.897. The lowest total risk was for azoxystrobin when applied at  0.0650 kg a.i. ha-1 (EF 0.625.

  20. Assessment of adjuvant ademetionine therapy for the bilirubin metabolism and target organ function of neonatal jaundice

    Directory of Open Access Journals (Sweden)

    Fang Xu

    2017-11-01

    Full Text Available Objective: To study the effect of adjuvant ademetionine (SAMe therapy on the bilirubin metabolism and target organ function of neonatal jaundice. Methods: A total of 68 children who were diagnosed with neonatal jaundice in Hubei Jianghan Oilfield General Hospital between March 2015 and April 2017 were selected as the research subjects and randomly divided into the SAMe group who received ademetionine combined with blue ray irradiation and the control group who received blue ray irradiation. The serum contents of bilirubin metabolism indexes and target organ injury markers before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of both groups were lower than those before treatment, and serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of SAMe group were lower than those of control group. Conclusion: Adjuvant ademetionine therapy can improve the bilirubin metabolism of neonatal jaundice and reduce the central nerve, myocardial and liver injury.

  1. Acute Toxicity of the Antifouling Compound Butenolide in Non-Target Organisms

    KAUST Repository

    Zhang, Yi-Fan

    2011-08-29

    Butenolide [5-octylfuran-2(5H)-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target) organisms. According to OECD\\'s guideline, the predicted no effect concentration (PNEC) was 0.168 µg l^(−1), which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish) embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK), Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound.

  2. Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

    OpenAIRE

    Raeker, Maide ?.; Russell, Mark W.

    2011-01-01

    During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish em...

  3. Impairment-targeted exercises for older adults with knee pain: a proof-of-principle study (TargET-Knee-Pain).

    Science.gov (United States)

    Wood, Laurence R J; Blagojevic-Bucknall, Milica; Stynes, Siobhán; D'Cruz, Deborah; Mullis, Ricky; Whittle, Rebecca; Peat, George; Foster, Nadine E

    2016-01-29

    Therapeutic exercise is an effective intervention for knee pain and osteoarthritis (OA) and should be individualised. In a preliminary, proof-of-principle study we sought to develop a home exercise programme targeted at specific physical impairments of weak quadriceps, reduced knee flexion range of motion (ROM) and poor balance, and evaluate whether receipt of this was associated with improvements in those impairments and in patient-reported outcomes among older adults with knee pain. This community-based study used a single group, before-after study design with 12-week follow-up. Participants were 58 adults aged over 56 years with knee pain and evidence of quadriceps weakness, loss of flexion ROM, or poor balance, recruited from an existing population-based, observational cohort. Participants received a 12-week home exercise programme, tailored to their physical impairments. The programme was led, monitored and progressed by a physiotherapist over six home visits, alternating with six telephone calls. Primary outcome measures were maximal isometric quadriceps strength, knee flexion ROM and timed single-leg standing balance, measured at baseline, 6 and 12 weeks by a research nurse blinded to the nature and content of participants' exercise programmes. Secondary outcome measures included the WOMAC. At 12 weeks, participants receiving strengthening exercises demonstrated a statistically significant change in quadriceps isometric strength compared to participants not receiving strengthening exercises: 3.9 KgF (95 % CI 0.1, 7.8). Changes in knee flexion ROM (2.1° (-2.3, 6.5)) and single-leg balance time (-2.4 s (-4.5, 6.7)) after stretching and balance retraining exercises respectively, were not found to be statistically significant. There were significant improvements in mean WOMAC Pain and Physical Function scores: -2.2 (-3.1, -1.2) and -5.1 (-7.8, -2.5). A 12-week impairment-targeted, home-based exercise programme for symptomatic knee OA appeared to be associated

  4. Callous-unemotional traits in children and mechanisms of impaired eye contact during expressions of love: a treatment target?

    Science.gov (United States)

    Dadds, Mark R; Allen, Jennifer L; McGregor, Kimberley; Woolgar, Matthew; Viding, Essi; Scott, Stephen

    2014-07-01

    We previously hypothesised that the early development of psychopathy is associated with a failure to attend to the eyes of attachment figures, and we have presented preliminary data from a parent-child 'love' scenario in support of this. Here, we confirm the association in a larger sample and test mechanisms of impaired eye contact during expressions of love in control and behaviourally disturbed children. Oppositional defiant disorder children, assessed for callous-unemotional (CU) traits, and controls, were observed in a brief interaction task where the mother was asked to show love to her child. Eye contact and affection were measured for each dyad. As predicted, there were no group differences in affection and eye contact expressed by mothers; levels of CU traits predicted low levels of eye contact towards their mothers across all groups of children. As expected, low eye contact was correlated with psychopathic fearlessness in their fathers, and maternal reports of negative feelings towards the child. Independent observations showed that child's behaviour largely drives the low eye contact associated with CU traits, and low eye contact was not associated with independent observations of the quality of attachment-related behaviours in mothers. Impaired eye contact is a unique characteristic of children with CU traits; these impairments are largely independent of maternal behaviour, but associated with psychopathic traits in the fathers. These impairments should be tested for functional significance and amenability to change in longitudinal and treatment studies. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

  5. Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein; impaired trafficking in a clinical isolate

    International Nuclear Information System (INIS)

    Caly, Leon; Kassouf, Vicki T.; Moseley, Gregory W.; Diefenbach, Russell J.; Cunningham, Anthony L.; Jans, David A.

    2016-01-01

    Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications. - Highlights: • HIV-1 Vpr utilizes the microtubule network to traffic towards the nucleus. • Mechanism relies on interaction between Vpr and dynein light chain protein DYNLT1. • Long-term non-progressor derived mutation (F72L) impairs this interaction. • Key residues in the vicinity of F72 contribute to interaction with DYNLT1.

  6. Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein; impaired trafficking in a clinical isolate

    Energy Technology Data Exchange (ETDEWEB)

    Caly, Leon [Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800 (Australia); Kassouf, Vicki T. [Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145 (Australia); Moseley, Gregory W. [Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800 (Australia); Diefenbach, Russell J.; Cunningham, Anthony L. [Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145 (Australia); Jans, David A., E-mail: david.jans@monash.edu [Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800 (Australia)

    2016-02-12

    Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications. - Highlights: • HIV-1 Vpr utilizes the microtubule network to traffic towards the nucleus. • Mechanism relies on interaction between Vpr and dynein light chain protein DYNLT1. • Long-term non-progressor derived mutation (F72L) impairs this interaction. • Key residues in the vicinity of F72 contribute to interaction with DYNLT1.

  7. Impaired functional organization in the visual cortex of muscarinic receptor knock-out mice.

    Science.gov (United States)

    Groleau, Marianne; Nguyen, Hoang Nam; Vanni, Matthieu P; Huppé-Gourgues, Frédéric; Casanova, Christian; Vaucher, Elvire

    2014-09-01

    Acetylcholine modulates maturation and neuronal activity through muscarinic and nicotinic receptors in the primary visual cortex. However, the specific contribution of different muscarinic receptor subtypes in these neuromodulatory mechanisms is not fully understood. The present study evaluates in vivo the functional organization and the properties of the visual cortex of different groups of muscarinic receptor knock-out (KO) mice. Optical imaging of intrinsic signals coupled to continuous and episodic visual stimulation paradigms was used. Retinotopic maps along elevation and azimuth were preserved among the different groups of mice. However, compared to their wild-type counterparts, the apparent visual field along elevation was larger in M2/M4-KO mice but smaller in M1-KO. There was a reduction in the estimated relative receptive field size of V1 neurons in M1/M3-KO and M1-KO mice. Spatial frequency and contrast selectivity of V1 neuronal populations were affected only in M1/M3-KO and M1-KO mice. Finally, the neuronal connectivity was altered by the absence of M2/M4 muscarinic receptors. All these effects suggest the distinct roles of different subtypes of muscarinic receptors in the intrinsic organization of V1 and a strong involvement of the muscarinic transmission in the detectability of visual stimuli. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. ASSESSING POSSIBLE ECOLOGICAL RISKS OF GENETICALLY MODIFIED CROPS: GENE EXPRESSION ASSAYS AND GENETIC MONITORING OF NON-TARGET ORGANISMS

    Science.gov (United States)

    Widespread planting of genetically modified crops with the Bt transgene pesticide has led to concern over non-target effects of Bt compounds in agroecosystems. While some research suggests that non-target organisms exposed to Bt toxin exhibit reduced fecundity and increased morta...

  9. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    NARCIS (Netherlands)

    G.B. Ehret (Georg); T. Ferreira (Teresa); D.I. Chasman (Daniel); A.U. Jackson (Anne); E.M. Schmidt (Ellen); T. Johnson (Toby); G. Thorleifsson (Gudmar); J. Luan (Jian'An); L.A. Donnelly (Louise); S. Kanoni (Stavroula); A.K. Petersen; V. Pihur (Vasyl); R.J. Strawbridge (Rona); D. Shungin (Dmitry); Hughes, M.F. (Maria F.); O. Meirelles; M. Kaakinen (Marika); N. Bouatia-Naji (Nabila); K. Kristiansson (Kati); S. Shah (Sonia); M.E. Kleber (Marcus); X. Guo (Xiuqing); L.-P. Lyytikäinen (Leo-Pekka); C. Fava (Cristiano); N. Eriksson (Niclas); I.M. Nolte (Ilja); P.K. Magnusson (Patrik); E. Salfati (Elias); L.S. Rallidis (Loukianos); Theusch, E. (Elizabeth); A.J.P. Smith; L. Folkersen (Lasse); H.E. Witkowska (Ewa); T.H. Pers (Tune); R. Joehanes (Roby); Kim, S.K. (Stuart K.); L. Lataniotis (Lazaros); R. Jansen; A.D. Johnson (Andrew); H. Warren (Helen); Y.J. Kim; Zhao, W. (Wei); Y. Wu (Ying); B. Tayo (Bamidele); M. Bochud (Murielle); D. Absher (Devin); L.S. Adair (Linda); N. Amin (Najaf); D.E. Arking (Dan); T. Axelsson (Tomas); D. Baldassarre (Damiano); B. Balkau (Beverley); S. Bandinelli (Stefania); M.J. Barnes (Michael); I. Barroso (Inês); Bevan, S. (Stephen); J.C. Bis (Joshua); Bjornsdottir, G. (Gyda); M. Boehnke (Michael); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); D.I. Boomsma (Dorret); S.R. Bornstein (Stefan); M.J. Brown (Morris); M. Burnier (Michel); Cabrera, C.P. (Claudia P.); J.C. Chambers (John); Chang, I.-S. (I-Shou); Cheng, C.-Y. (Ching-Yu); P.S. Chines (Peter); Chung, R.-H. (Ren-Hua); F.S. Collins (Francis); Connell, J.M. (John M.); A. Döring (Angela); J. Dallongeville; J. Danesh (John); U. de Faire (Ulf); G. Delgado; A. Dominiczak (Anna); A.S.F. Doney (Alex); F. Drenos (Fotios); T. Edkins (Ted); Eicher, J.D. (John D.); R. Elosua (Roberto); S. Enroth (Stefan); J. Erdmann (Jeanette); P. Eriksson (Per); T. Esko (Tõnu); E. Evangelou (Evangelos); A. Evans (Alun); M. Fall (Magnus); M. Farrall (Martin); J.F. Felix (Janine); J. Ferrieres (Jean); L. Ferrucci (Luigi); M. Fornage (Myriam); T. Forrester (Terrence); N. Franceschini (Nora); O.H. Franco (Oscar); A. Franco-Cereceda (Anders); R.M. Fraser (Ross); S.K. Ganesh (Santhi); Gao, H. (He); K. Gertow (Karl); F. Gianfagna (Francesco); B. Gigante (Bruna); F. Giulianini (Franco); A. Goel (Anuj); A.H. Goodall (Alison); M. Goodarzi (Mark); M. Gorski (Mathias); J. Gräßler (Jürgen); C.J. Groves (Christopher); V. Gudnason (Vilmundur); U. Gyllensten (Ulf); G. Hallmans (Göran); A.L. Hartikainen; Hassinen, M. (Maija); A.S. Havulinna (Aki); C. Hayward (Caroline); S. Hercberg (Serge); K.H. Herzig; A.A. Hicks (Andrew); A. Hingorani (Aroon); J.N. Hirschhorn (Joel); Hofman, A. (Albert); Holmen, J. (Jostein); O.L. Holmen (Oddgeir); J.J. Hottenga (Jouke Jan); P. Howard (Philip); Hsiung, C.A. (Chao A.); S.C. Hunt (Steven); M.K. Ikram (Kamran); T. Illig (Thomas); C. Iribarren (Carlos); Jensen, R.A. (Richard A.); M. Kähönen (Mika); H.M. Kang (Hyun Min); S. Kathiresan (Sekar); J. Keating (John); K.T. Khaw; Y.K. Kim (Yun Kyoung); E. Kim (Eric); M. Kivimaki (Mika); N. Klopp (Norman); Kolovou, G. (Genovefa); P. Komulainen (Pirjo); J.S. Kooner (Jaspal S.); Kosova, G. (Gulum); R.M. Krauss (Ronald); D. Kuh (Diana); Z. Kutalik (Zoltán); J. Kuusisto (Johanna); K. Kvaløy (Kirsti); T.A. Lakka (Timo); N.R. Lee (Nanette); I.T. Lee; W.-J. Lee (Wen-Jane); D. Levy (Daniel); X. Li (Xiaohui); Liang, K.-W. (Kae-Woei); Lin, H. (Honghuang); Lin, L. (Li); J. Lindström (Jaana); S. Lobbens (Stéphane); S. Männistö (Satu); G. Müller (Gabriele); M. Müller-Nurasyid (Martina); F. MacH (François); H.S. Markus (Hugh); E. Marouli (Eirini); M.I. McCarthy (Mark); C.A. McKenzie (Colin); P. Meneton (Pierre); C. Menni (Cristina); A. Metspalu (Andres); Mijatovic, V. (Vladan); L. Moilanen (Leena); M.E. Montasser (May E.); A.D. Morris (Andrew); A.C. Morrison (Alanna); Mulas, A. (Antonella); R. Nagaraja (Ramaiah); N. Narisu (Narisu); K. Nikus (Kjell); C.J. O'Donnell (Christopher); P.F. O'Reilly (Paul); K.K. Ong (Ken); Paccaud, F. (Fred); C. Palmer (Cameron); A. Parsa (Afshin); N.L. Pedersen (Nancy); B.W.J.H. Penninx (Brenda); M. Perola (Markus); A. Peters (Annette); N.R. Poulter (Neil); P.P. Pramstaller (Peter Paul); B.M. Psaty (Bruce); T. Quertermous (Thomas); D.C. Rao (Dabeeru C.); A. Rasheed (Asif); N.W. Rayner (Nigel William); F. Renström (Frida); R. Rettig (Rainer); K.M. Rice (Kenneth); R. Roberts (Robert); L.M. Rose (Lynda); Rossouw, J. (Jacques); N.J. Samani (Nilesh); S. Sanna (Serena); J. Saramies (Jouko); H. Schunkert (Heribert); S. Sebert (Sylvain); Sheu, W.H.-H. (Wayne H.-H.); Shin, Y.-A. (Young-Ah); X. Sim (Xueling); G.D. Smith; A.V. Smith (Albert Vernon); M.X. Sosa (Maria X.); T.D. Spector (Timothy); A. Stancáková (Alena); A. Stanton (Alice); K. Stirrups (Kathy); H.M. Stringham (Heather); Sundstrom, J. (Johan); A.J. Swift (Amy); A.C. Syvänen; Tai, E.-S. (E-Shyong); T. Tanaka (Toshiko); K.V. Tarasov (Kirill); A. Teumer (Alexander); U. Thorsteinsdottir (Unnur); M.D. Tobin (Martin); E. Tremoli (Elena); Uitterlinden, A.G. (Andre G.); M. Uusitupa (Matti); A. Vaez (Ahmad); D. Vaidya (Dhananjay); Van Duijn, C.M. (Cornelia M.); E.P.A. van Iperen (Erik); Vasan, R.S. (Ramachandran S.); G.C. Verwoert (Germaine); J. Virtamo (Jarmo); Vitart, V. (Veronique); B.F. Voight (Benjamin); P. Vollenweider (Peter); Wagner, A. (Aline); Wain, L.V. (Louise V.); N.J. Wareham (Nick); H. Watkins (Hugh); A.B. Weder (Alan); H.J. Westra (Harm-Jan); Wilks, R. (Rainford); T. Wilsgaard (Tom); J.F. Wilson (James F.); Wong, T.Y. (Tien Y.); T.-P. Yang (Tsun-Po); J. Yao (Jiefen); L. Yengo (Loic); W. Zhang (Weihua); J.H. Zhao (Jing Hua); X. Zhu (Xiaofeng); P. Bovet (Pascal); Cooper, R.S. (Richard S.); K.L. Mohlke (Karen); Saleheen, D. (Danish); J.-Y. Lee (Jong-Young); P. Elliott (Paul); L.M. Gierman (Lobke); C.J. Willer (Cristen); L. Franke (Lude); G. Kees Hovingh; K.D. Taylor (Kent); G.V. Dedoussis (George); P. Sever (Peter); A. Wong (Andrew); W.H.L. Kao (Wen); T.L. Assimes (Themistocles); I. Njølstad (Inger); P.E.H. Schwarz (Peter); C. Langenberg (Claudia); H. Snieder (Harold); M. Caulfield (Mark); O. Melander (Olle); M. Laakso (Markku); J. Saltevo (Juha); R. Rauramaa (Rainer); J. Tuomilehto (Jaakko); Ingelsson, E. (Erik); T. Lehtimäki (Terho); K. Hveem (Kristian); W. Palmas (Walter); W. März (Winfried); M. Kumari (Meena); V. Salomaa (Veikko); Y.D. Chen (Y.); Rotter, J.I. (Jerome I.); P. Froguel (Philippe); M.-R. Jarvelin (Marjo-Riitta); E. Lakatta (Edward); K. Kuulasmaa (Kari); P.W. Franks (Paul); A. Hamsten (Anders); H.E. Wichmann (Heinz Erich); C.N.A. Palmer (Colin); Stefansson, K. (Kari); P.M. Ridker (Paul); R.J.F. Loos (Ruth); A. Chakravarti (Aravinda); P. Deloukas (Panagiotis); A.P. Morris (Andrew); C. Newton-Cheh (C.); P. Munroe (Patricia)

    2016-01-01

    textabstractTo dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We

  10. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    NARCIS (Netherlands)

    Ehret, Georg B.; Ferreira, Teresa; Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Louise A.; Kanoni, Stavroula; Petersen, Ann -Kristin; Pihurl, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikainen, Leo-Pekka; Fava, Cristiano; Eriksson, Nidas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J. P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arkingl, Dan E.; Axelsson, Tomas; Baldassarre, Damian; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Ines; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S.; Chung, Ren-Hua; Collins, Francis S.; Connell, John M.; Doring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S. F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fai, Tove; Farra, Martin; Felixl, Janine F.; Ferrieres, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschinil, Nora; Franco, Oscar H.; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goe, Anuj; Goodall, Alison H.; Goodarzi, Mark; Gorski, Mathias; Grassler, Jurgen; Groves, Christopher J.; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Goran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofmanl, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven C.; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kahonen, Mika; Kang, Hyun Min; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaloy, Kirsti; Lakka, Timo A.; Lee, Nanette R.; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindstrom, Jaana; Lobbens, Stephane; Mannisto, Satu; Muller, Gabriele; Muller-Nurasyid, Martina; Mach, Francois; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N. William; Renstrom, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H-H; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stancakova, Alena; Stanton, Alice V.; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvanen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M.; van Iperen, Erik P. A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watldns, Hugh; Weder, Alan B.; Westra, Harm Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G. Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njolstad, Inger; Schwarz, Peter E. H.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, E.; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimaki, Terho; Hveem, Kristian; Palmas, Walter; Marz, Winfried; Kumar, Meena; Salomaa, Veikko; Chen, Yii-Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H-Erich; Palmer, Colin N. A.; Stefansson, Kari; Ridker, Paul M.; Loos, Ruth J. F.; Chalcravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

    2016-01-01

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66

  11. Skin: Major target organ of allergic reactions to small molecular weight compounds

    International Nuclear Information System (INIS)

    Merk, Hans F.; Baron, Jens M.; Neis, Mark M.; Obrigkeit, Daniela Hoeller; Karlberg, Ann-Therese

    2007-01-01

    Skin is a major target organ for allergic reactions to small molecular weight compounds. Drug allergic reactions may be life-threatening such as in the case of anaphylactic reactions or bullous drug reactions and occur in about 5% of all hospitalized patients. Allergic contact dermatitis has an enormous influence on the social life of the patient because it is the most frequent reason for occupational skin diseases and the treatment and prevention of this disease cost approximately Euro 3 billion per year in Germany. The different proposed pathophysiological pathways leading to a drug eruption are discussed in this paper. All major enzymes which are involved in the metabolism of xenobiotica were shown to be present in skin. Evidence supporting the role of metabolism in the development of drug allergy and allergic contact dermatitis is demonstrated in the example of sulphonamides and fragrances

  12. Scientific activity within the targeted research project: Metallic, ceramic and organic nanomaterials: processing - structure - properties - applications

    International Nuclear Information System (INIS)

    Leonowicz, M.; Kurzydlowski, K.

    2003-01-01

    In november 2000 Polish State Committee for Scientific Research (KBN) launched a Targeted Research Project 'Metallic, ceramic and organic nanomaterials: processing - structure - properties - applications'. The structural materials, covered by the project, comprise analysis of the suitability of heavy deformation routes for nanocrystallization of metals and alloys, Al-based glass-ceramics, ceramic matrix nanocomposites, gradient materials. Also surface engineering methods and polymer matrix nanocomposites are studied. Novel methods for the processing and compacting of nanomaterials are also researched. Among functional materials: materials for batteries soft and hard magnetic materials and nanomaterials, giant magnetoresistance and light emitting materials are studied. Basic phenomena such as mechanics of superplastic deformation of ceramics, demagnetization processes in ferromagnetic nanomaterials, transport processes in ionic conductivity materials are also investigated. Overview of the main research direction and selected achievements of the project are presented. (author)

  13. Influence of salt intake on target organ damages in treated hypertensive patients.

    Science.gov (United States)

    Ohta, Yuko; Tsuchihashi, Takuya; Kiyohara, Kanako

    2012-01-01

    This study investigates the influence of salt intake on renin-angiotensin-aldosterone system and clarifies their role to the target organ damage in the treated hypertensive patients. Subjects were 188 treated hypertensive outpatients (96 females and 92 males, mean age 67 ± 11 y). Patients underwent 24-hour home urine collection to measure urinary salt excretion and proteinuria. Clinical blood pressure (BP) and blood chemistry including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined. Left ventricular mass index (LVMI) was also determined by echocardiography. Average BP was 129 ± 16/68 ± 10 mm Hg with the use of 2.0 antihypertensive drugs on average. Urinary salt excretion, PRA, and PAC were 8.1 ± 3.2 g/day, 2.2 ± 2.8 ng/mL/h, and 112 ± 54 pg/mL, respectively. Even in the patients taking angiotensin receptor blocker or angiotensin-converting enzyme inhibitors (n = 146), 15.1% showed low PRA (salt excretion in these patients with low PRA (9.1 ± 4.2 g/day) did not differ from those with higher PRA levels (8.2 ± 2.6 g/day, NS). There was no correlation between salt excretion and PRA (r = 0.03, NS), while salt excretion showed a significant negative correlation to PAC (r = -0.17, P salt excretion was also correlated with proteinuria (r = 0.25, P salt excretion contributed to proteinuria (P salt intake in Japanese patients treated with antihypertensive drugs. Since high salt intake was possibly associated with target organ damages, strict salt reduction should be encouraged.

  14. Molecular effects and bioaccumulation of levonorgestrel in the non-target organism Dreissena polymorpha

    Energy Technology Data Exchange (ETDEWEB)

    Contardo-Jara, Valeska, E-mail: contardo@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Lorenz, Claudia, E-mail: claudia.lorenz@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Pflugmacher, Stephan, E-mail: pflugmacher@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Nuetzmann, Gunnar, E-mail: nuetzmann@igb-berlin.d [Department of Ecohydrology, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Kloas, Werner, E-mail: werner.kloas@igb-berlin.d [Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Wiegand, Claudia, E-mail: wiegand@biology.sdu.d [University of Southern Denmark, Institute of Biology, Campusvej 55, 5230 Odense M (Denmark)

    2011-01-15

    Bioaccumulation and effects of the contraceptive hormone levonorgestrel were examined in the non-target organism Dreissena polymorpha. Molecular biomarkers of biotransformation, elimination, antioxidant defence and protein damage were analyzed after exposure to increasing concentrations of levonorgestrel in a flow-through system. The lowest concentration (0.312 {mu}g L{sup -1}) was 100-fold bioconcentrated within four days. A decrease of the bioconcentration factor was observed within one week for the highest test concentrations (3.12 and 6.24 {mu}g L{sup -1}) suggesting enhanced excretory processes. The immediate mRNA up-regulation of pi class glutathione S-transferase proved that phase II biotransformation processes were induced. Disturbance of fundamental cell functions was assumed since the aryl hydrocarbon receptor has been permanently down-regulated. mRNA up-regulation of P-glycoprotein, superoxide dismutase and metallothioneine suggested enhanced elimination processes and ongoing oxidative stress. mRNA up-regulation of heat shock protein 70 in mussels exposed to the two highest concentrations clearly indicated impacts on protein damage. - Fundamental cell processes as biotransformation, elimination and prevention from oxidative stress are influenced by exposure of the contraceptive levonorgestrel in non-target organisms. - Research highlights: Bioaccumulation of levonorgestrel in mussels is higher than expected based on its lipophilicity. Exposure to levonorgestrel causes oxidative stress and enhanced elimination processes. Glutathione S-transferase (pi class) mRNA induction after one day hint on phase II biotransformation. mRNA induction of heat shock protein 70 after one week prove protein damage.

  15. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

    Directory of Open Access Journals (Sweden)

    Qi Wang

    Full Text Available BACKGROUND: To investigate if microRNAs (miRNAs play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+ current. RESULTS: H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2, with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. CONCLUSIONS: Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

  16. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

    Science.gov (United States)

    Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

    2013-01-01

    To investigate if microRNAs (miRNAs) play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+) current. H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2), with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

  17. Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease

    Directory of Open Access Journals (Sweden)

    Speranza Rubattu

    2016-01-01

    Full Text Available Mechanisms underlying hypertensive target organ damage (TOD are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2 involved in OXPHOS complex I assembly and activity and the second one (UCP2 involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension.

  18. Monitoring the World Health Organization Global Target 2025 for Exclusive Breastfeeding: Experience From the United States.

    Science.gov (United States)

    Gupta, Priya M; Perrine, Cria G; Chen, Jian; Elam-Evans, Laurie D; Flores-Ayala, Rafael

    2017-08-01

    Exclusive breastfeeding under 6 months, calculated from a single 24-hour recall among mothers of children 0 to 5 months of age, is a World Health Organization (WHO) indicator used to monitor progress on the 2025 global breastfeeding target. Many upper-middle-income and high-income countries, including the United States, do not have estimates for this indicator. Research aim: To describe the prevalence of exclusive breastfeeding under 6 months in the United States. We used a single 24-hour dietary recall from the National Health and Nutrition Examination Survey 2009-2012 to calculate the prevalence of exclusive breastfeeding under 6 months. We discuss our results in the context of routine breastfeeding surveillance, which is reported from a national survey with different methodology. Among children younger than 6 months, 24.4%, 95% confidence interval [17.6, 31.1], were exclusively breastfed the previous day. To our knowledge, this is the first estimate of the WHO indicator of exclusive breastfeeding under 6 months for the United States. This study supports the global surveillance and data strategy for reporting to the WHO on the 2025 target for exclusive breastfeeding.

  19. Evaluation of polar organic micropollutants as indicators for wastewater-related coastal water quality impairment

    International Nuclear Information System (INIS)

    Nödler, Karsten; Tsakiri, Maria; Aloupi, Maria; Gatidou, Georgia; Stasinakis, Athanasios S.; Licha, Tobias

    2016-01-01

    Results from coastal water pollution monitoring (Lesvos Island, Greece) are presented. In total, 53 samples were analyzed for 58 polar organic micropollutants such as selected herbicides, biocides, corrosion inhibitors, stimulants, artificial sweeteners, and pharmaceuticals. Main focus is the application of a proposed wastewater indicator quartet (acesulfame, caffeine, valsartan, and valsartan acid) to detect point sources and contamination hot-spots with untreated and treated wastewater. The derived conclusions are compared with the state of knowledge regarding local land use and infrastructure. The artificial sweetener acesulfame and the stimulant caffeine were used as indicators for treated and untreated wastewater, respectively. In case of a contamination with untreated wastewater the concentration ratio of the antihypertensive valsartan and its transformation product valsartan acid was used to further refine the estimation of the residence time of the contamination. The median/maximum concentrations of acesulfame and caffeine were 5.3/178 ng L −1 and 6.1/522 ng L −1 , respectively. Their detection frequency was 100%. Highest concentrations were detected within the urban area of the capital of the island (Mytilene). The indicator quartet in the gulfs of Gera and Kalloni (two semi-enclosed embayments on the island) demonstrated different concentration patterns. A comparatively higher proportion of untreated wastewater was detected in the gulf of Gera, which is in agreement with data on the wastewater infrastructure. The indicator quality of the micropollutants to detect wastewater was compared with electrical conductivity (EC) data. Due to their anthropogenic nature and low detection limits, the micropollutants are superior to EC regarding both sensitivity and selectivity. The concentrations of atrazine, diuron, and isoproturon did not exceed the annual average of their environmental quality standards (EQS) defined by the European Commission. At two

  20. Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both β-amyloid production and clearance.

    Science.gov (United States)

    Zhu, Zhiyuan; Yan, Jianming; Jiang, Wei; Yao, Xin-gang; Chen, Jing; Chen, Lili; Li, Chenjing; Hu, Lihong; Jiang, Hualiang; Shen, Xu

    2013-08-07

    Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

  1. Impaired activity of bile bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat

    NARCIS (Netherlands)

    Koopen, NR; Wolters, H; Havinga, R; Vonk, RJ; Jansen, PLM; Muller, M; Kuipers, F

    To test the hypothesis that impaired activity of the bile canalicular organic anion transporting system mrp2 (cmoat) is a key event in the etiology of 17 alpha-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats, EE (5 mg/kg subcutaneously daily) was administered to male normal Wistar

  2. Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Bosch, Walter [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Roberge, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Haas, Rick L.M. [Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Catton, Charles N. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Indelicato, Daniel J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Olsen, Jeffrey R. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Deville, Curtiland [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Chen, Yen-Lin [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Finkelstein, Steven E. [Translational Research Consortium, 21st Century Oncology, Scottsdale, Arizona (United States); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Wang, Dian [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States)

    2015-08-01

    Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.

  3. Shift of graft-versus-host-disease target organ tropism by dietary vitamin A.

    Directory of Open Access Journals (Sweden)

    Christian Koenecke

    Full Text Available Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT. Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-α4β7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD. The course of GvHD was ameliorated in VAD HSCT-recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-γ(+CD4(+ and low FoxP3(+CD4(+ frequencies of total donor CD4(+ T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT.

  4. Late multiple organ surge in interferon-regulated target genes characterizes staphylococcal enterotoxin B lethality.

    Directory of Open Access Journals (Sweden)

    Gabriela A Ferreyra

    Full Text Available BACKGROUND: Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB challenge was investigated in six tissues. RESULTS: The earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC, spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RT-PCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN/antiviral-response and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature. CONCLUSION: Global gene-expression changes across multiple organs implicated a host-wide IFN-response in SEB-induced death. Therapies aimed at IFN-associated innate immunity may improve outcome in toxic shock syndromes.

  5. The preparation of accelerator targets by the evaporation of acetate-organic solutions in the presence of NH3 gas

    International Nuclear Information System (INIS)

    Cai, S.Y.; Ghiorso, A.; Hoffman, D.C.

    1987-03-01

    The chemical methods described in this paper have been developed for preparation of isotopic targets for bombardment by accelerator-produced ions. Three systems are compared: nitrate-, chloride-, and acetate-organic solutions. The best method was found to be the metallic acetate-organic solution system, evaporated onto the substrate in the presence of ammonia gas. A detailed procedure is given for this method. The targets obtained by the acetate-organic solution system are uniform and adherent. The hydroxide forms fine crystals of good quality for target thicknesses from a few μg/cm 2 to several mg/cm 2 . Thicknesses up to 5 mg/cm 2 of Eu as the oxide were obtained by this method. The process is simple and fast. 18 refs., 1 tab

  6. Target organ localization of memory CD4(+) T cells in patients with chronic beryllium disease.

    Science.gov (United States)

    Fontenot, Andrew P; Canavera, Scott J; Gharavi, Laia; Newman, Lee S; Kotzin, Brian L

    2002-11-01

    Chronic beryllium disease (CBD) is caused by exposure to beryllium in the workplace, and it remains an important public health concern. Evidence suggests that CD4(+) T cells play a critical role in the development of this disease. Using intracellular cytokine staining, we found that the frequency of beryllium-specific CD4(+) T cells in the lungs (bronchoalveolar lavage) of 12 CBD patients ranged from 1.4% to 29% (mean 17.8%), and these T cells expressed a Th1-type phenotype in response to beryllium sulfate (BeSO(4)). Few, if any, beryllium-specific CD8(+) T cells were identified. In contrast, the frequency of beryllium-responsive CD4(+) T cells in the blood of these subjects ranged from undetectable to 1 in 500. No correlation was observed between the frequency of beryllium-responsive bronchoalveolar lavage (BAL) CD4(+) T cells as detected by intracellular staining and lymphocyte proliferation in culture after BeSO(4) exposure. Staining for surface marker expression showed that nearly all BAL T cells exhibit an effector memory cell phenotype. These results demonstrate a dramatically high frequency and compartmentalization of antigen-specific effector memory CD4(+) cells in the lungs of CBD patients. These studies provide insight into the phenotypic and functional characteristics of antigen-specific T cells invading other inaccessible target organs in human disease.

  7. Next-generation phylogeography: a targeted approach for multilocus sequencing of non-model organisms.

    Directory of Open Access Journals (Sweden)

    Jonathan B Puritz

    Full Text Available The field of phylogeography has long since realized the need and utility of incorporating nuclear DNA (nDNA sequences into analyses. However, the use of nDNA sequence data, at the population level, has been hindered by technical laboratory difficulty, sequencing costs, and problematic analytical methods dealing with genotypic sequence data, especially in non-model organisms. Here, we present a method utilizing the 454 GS-FLX Titanium pyrosequencing platform with the capacity to simultaneously sequence two species of sea star (Meridiastra calcar and Parvulastra exigua at five different nDNA loci across 16 different populations of 20 individuals each per species. We compare results from 3 populations with traditional Sanger sequencing based methods, and demonstrate that this next-generation sequencing platform is more time and cost effective and more sensitive to rare variants than Sanger based sequencing. A crucial advantage is that the high coverage of clonally amplified sequences simplifies haplotype determination, even in highly polymorphic species. This targeted next-generation approach can greatly increase the use of nDNA sequence loci in phylogeographic and population genetic studies by mitigating many of the time, cost, and analytical issues associated with highly polymorphic, diploid sequence markers.

  8. Analysis of the interactions between environmental and food contaminants, cadmium and deoxynivalenol, in different target organs.

    Science.gov (United States)

    Le, Thanh-Huong; Alassane-Kpembi, Imourana; Oswald, Isabelle P; Pinton, Philippe

    2018-05-01

    Cadmium (Cd), a common and widespread toxic heavy metal, and mycotoxins such as deoxynivalenol (DON) are frequent contaminants of the food supply. Most of the data on their toxicity concern their effects when present alone. However, consumers can be exposed to a cocktail of DON and Cd. To improve the understanding of their combined toxicity, the effects of DON and Cd alone or in combination were investigated in different human cell lines from the kidney (HEK-293), intestine (Caco-2), blood (HL-60) and liver (HepG2). Cytotoxicity was assessed through ATP measurement and types of interactions determined by the Isobologram-Combination index method. HEK-293 cells were exposed to increasing doses of DON, Cd and their combination at different ratios (DON/Cd of 2/1; 1/1; 1/2 and 1/8). Regardless of the ratio, the type of interaction observed in HEK-293 cells ranged from moderate antagonism to nearly additive with increasing cytotoxicity. In Caco-2 cells, the interactions ranged from nearly additive to antagonism whatever the ratio. At ratio 1/1, in HL-60 and HepG2 cells, interactions ranged from synergy to antagonism depending on the cytotoxicity level. Using human cells lines, this study indicates that the consequences of combined exposure to environmental and food contaminants are specific to the target organ. Further studies are needed to confirm these data in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Adropin levels and target organ damage secondary to high blood pressure in the ED.

    Science.gov (United States)

    Gulen, Bedia; Eken, Cenker; Kucukdagli, Okkes Taha; Serinken, Mustafa; Kocyigit, Abdurrahim; Kılıc, Elif; Uyarel, Hüseyin

    2016-11-01

    High blood pressure is still a challenge for emergency physicians to discern the patients that require further analysis to establish the existence of acute hypertensive target organ damage (TOD). The present study aimed to reveal that adropin levels are useful for detecting TOD in patients presenting with high blood pressure. Patients presenting with a blood pressure of more than 180/110 mm Hg were enrolled into the study. After a resting period of 15 minutes, patients' blood pressures were measured thrice at 5-minute intervals while the patients were sitting on a chair, and the average of these measurements was accepted as the baseline value. Blood samples were obtained for either adropin levels or possible TOD during the emergency department admission. A total of 119 patients were included in the study. The mean systolic and diastolic blood pressures of study patients were 204.8±23.2 and 108.3 ± 10.3, respectively, and 42% (n = 50) of the patients had TOD. Although the adropin levels were similar between the patients with or without TOD (TOD group = 195 pg/mL, interquartile range [IQR]: 178-201; no-TOD group = 196 pg/mL, IQR: 176-204 [P = .982]), it is significantly higher in normotensive patients (normotensive group = 289 pg/mL, IQR: 193-403) compared with the hypertensive ones (P high blood pressure to the emergency department. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

    Science.gov (United States)

    Dines, M; Lamprecht, R

    2014-09-30

    Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

  11. Target organ specific activity of drosophila MRP (ABCC1) moderates developmental toxicity of methylmercury.

    Science.gov (United States)

    Prince, Lisa; Korbas, Malgorzata; Davidson, Philip; Broberg, Karin; Rand, Matthew Dearborn

    2014-08-01

    Methylmercury (MeHg) is a ubiquitous and persistent neurotoxin that poses a risk to human health. Although the mechanisms of MeHg toxicity are not fully understood, factors that contribute to susceptibility are even less well known. Studies of human gene polymorphisms have identified a potential role for the multidrug resistance-like protein (MRP/ABCC) family, ATP-dependent transporters, in MeHg susceptibility. MRP transporters have been shown to be important for MeHg excretion in adult mouse models, but their role in moderating MeHg toxicity during development has not been explored. We therefore investigated effects of manipulating expression levels of MRP using a Drosophila development assay. Drosophila MRP (dMRP) is homologous to human MRP1-4 (ABCC1-4), sharing 50% identity and 67% similarity with MRP1. A greater susceptibility to MeHg is seen in dMRP mutant flies, demonstrated by reduced rates of eclosion on MeHg-containing food. Furthermore, targeted knockdown of dMRP expression using GAL4>UAS RNAi methods demonstrates a tissue-specific function for dMRP in gut, Malpighian tubules, and the nervous system in moderating developmental susceptibility to MeHg. Using X-ray synchrotron fluorescence imaging, these same tissues were also identified as the highest Hg-accumulating tissues in fly larvae. Moreover, higher levels of Hg are seen in dMRP mutant larvae compared with a control strain fed an equivalent dose of MeHg. In sum, these data demonstrate that dMRP expression, both globally and within Hg-targeted organs, has a profound effect on susceptibility to MeHg in developing flies. Our findings point to a potentially novel and specific role for dMRP in neurons in the protection against MeHg. Finally, this experimental system provides a tractable model to evaluate human polymorphic variants of MRP and other gene variants relevant to genetic studies of mercury-exposed populations. © The Author 2014. Published by Oxford University Press on behalf of the Society of

  12. Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Houbao [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Xu, Wangyang [Department of Clinical Laboratories, Ninth People’s Hospital, SJTUSM, Shanghai 200011 (China); Zhang, Hongxin [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Liu, Jianbing [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Shanghai Research Center for Model Organisms, Shanghai 201203 (China); Xu, Haimin [Department of Pathology, Rui-Jin Hospital, SJTUSM, Shanghai 200025 (China); Lu, Shunyuan; Dang, Suying [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Kuang, Ying [Shanghai Research Center for Model Organisms, Shanghai 201203 (China); Jin, Xiaolong [Department of Pathology, Rui-Jin Hospital, SJTUSM, Shanghai 200025 (China); Wang, Zhugang, E-mail: zhugangw@shsmu.edu.cn [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Shanghai Research Center for Model Organisms, Shanghai 201203 (China)

    2013-08-16

    Highlights: •Kif18A is up-regulated in CAC of mouse model. •Kif18a{sup −/−} mice are protected from CAC. •Tumor cells from Kif18a{sup −/−} mice undergo more apoptosis. •Kif18A deficiency induces poor Atk phosphorylation. -- Abstract: Kinesins are a superfamily of molecular motors involved in cell division or intracellular transport. They are becoming important targets for chemotherapeutic intervention of cancer due to their crucial role in mitosis. Here, we demonstrate that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently protected from AOM–DSS-induced colon carcinogenesis. Kif18A is responsible for proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell apoptosis. Mechanistically, Kif18a is responsible for induction of Akt phosphorylation, which is known to be associated with cell survival regulation. In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A activity may be useful in the prevention or chemotherapeutic intervention of CAC.

  13. MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Pasqualino de Antonellis

    Full Text Available Through negative regulation of gene expression, microRNAs (miRNAs can function as oncosuppressors in cancers, and can themselves show altered expression in various tumor types. Here, we have investigated medulloblastoma tumors (MBs, which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many of the cell-fate-determining stages. Notch regulates a subset of MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulate these phenomena, and can be used in anti-cancer therapies.In a screening of potential targets within Notch signaling, miR-34a was seen to be a regulator of the Notch pathway through its targeting of Notch ligand Delta-like 1 (Dll1. Down-regulation of Dll1 expression by miR-34a negatively regulates cell proliferation, and induces apoptosis and neural differentiation in MB cells. Using an inducible tetracycline on-off model of miR-34a expression, we show that in Daoy MB cells, Dll1 is the first target that is regulated in MB, as compared to the other targets analyzed here: Cyclin D1, cMyc and CDK4. MiR-34a expression negatively affects CD133(+/CD15(+ tumor-propagating cells, then we assay through reverse-phase proteomic arrays, Akt and Stat3 signaling hypo-phosphorylation. Adenoviruses carrying the precursor miR-34a induce neurogenesis of tumor spheres derived from a genetic animal model of MB (Patch1(+/- p53(-/-, thus providing further evidence that the miR-34a/Dll1 axis controls both autonomous and non autonomous signaling of Notch. In vivo, miR-34a overexpression carried by adenoviruses reduces tumor burden in cerebellum xenografts of athymic mice, thus demonstrating an anti-tumorigenic role of miR-34a in vivo.Despite advances in our understanding of the pathogenesis of MB, one-third of patients with MB remain incurable. Here, we show that stable nucleic

  14. MLC tracking for lung SABR reduces planning target volumes and dose to organs at risk.

    Science.gov (United States)

    Caillet, Vincent; Keall, Paul J; Colvill, Emma; Hardcastle, Nicholas; O'Brien, Ricky; Szymura, Kathryn; Booth, Jeremy T

    2017-07-01

    Assess the dosimetric impact of multi-leaf collimator (MLC) tracking and mid-ventilation (midV) planning compared with the internal target volume (ITV)-based planning approach for lung Stereotactic Ablative Body Radiotherapy (SABR). Ten lung SABR patients originally treated with an ITV-based plan were re-planned according to MLC tracking and midV planning schemes. All plans were delivered on a linac to a motion phantom in a simulated treatment with real lung motions. Delivered dose was reconstructed in patient planning scans. ITV-based, tracking and midV regimes were compared at the planning and delivered stages based on PTV volume and dose metrics for the GTV and OAR. MLC tracking and midV schemes yielded favourable outcomes compared with ITV-based plans. Average reduction in PTV volume was (MLC tracking/MidV) 33.9%/22%. GTV dose coverage performed better with MLC tracking than the other regimes. Reduction in dose to OAR were for the lung (mean lung dose, 0.8Gy/0.2Gy), oesophagus (D3cc, 1.9Gy/1.4Gy), great vessels (D10cc, 3.2Gy/1.3Gy), trachea (D4cc, 1.1Gy/0.9Gy), heart (D1cc, 2.0Gy/0.5Gy) and spinal cord (D0.03cc, 0.5Gy/-0.1Gy). MLC tracking showed reduction in PTV volume, superior GTV dose coverage and organ dose sparing than MidV and ITV-based strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Henrique Tria Bianco

    2014-10-01

    Full Text Available Background: Patients with diabetes are in extract higher risk for fatal cardiovascular events. Objective: To evaluate major predictors of mortality in subjects with type 2 diabetes. Methods: A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR and confidence interval (CI related to cardiovascular and total mortality. Results: After 9.2 years of follow-up (median, 33 subjects died (17 from cardiovascular causes. Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019; prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007; eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001; long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004; and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002. Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030; smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046; prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005, and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017. Conclusions: Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.

  16. The relationship between metabolic syndrome and target organ damage in Ghanaian with stage-2 hypertension.

    Science.gov (United States)

    Bello-Rodriguez, B M; Sanchez-Cruz, G; Delgado-Bustillo, F; Asiama, G

    2013-12-01

    To determine the frequency of Metabolic syndrome (MetS) in stage-2 hypertension and to assess the influence of MetS components over target organ damage (TOD) in Ghanaian patients. Forty adult patients with stage-2 hypertension were enrolled in a cross-sectional study developed at the Police Hospital, Accra, between 1st February 2009 and 31st January 2010. Diagnosis of MetS was based on The National Cholesterol Education Program in Adult Treatment Panel Revised in 2005 criteria. The alterations on the heart, aortic and carotid arteries, retina, and kidneys were evaluated through the clinical examination including retinal funduscopy, chest X-Ray, ECG, and serum creatinine quantification. The Brain CT-scan was performed on the patients with clinical cerebrovascular disease manifestations. MetS was diagnosed in 25 cases (62.5%); female sex revealed significant association with MetS (OR, 4.88; 95% CI, 1.19-19.94; P=0.027). Ninety-five percent of patients had TOD. Coronary disease was associated with MetS (OR, 4.43; 95% CI, 1.026-19,27; P=0.047) and diabetes mellitus as single MetS component (OR, 14.00; 95% CI, 1.56-125.61; P=0.018). A positive significant correlation was shown of age with cerebrovascular disease (r=0.381; P=0.015) and coronary disease (r=0.623; P=0.000). Non-significant correlation or association (P>0.05) was shown between number of MetS components and number of TOD. In stage-2 hypertension patients a high frequency of MetS with a risk increase in female sex was observed. This stage hypertension is for itself an individual risk to develop cardiovascular disease with high frequency none related with MetS, although coronary disease risk was increased in diabetic patients.

  17. Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Bianco, Henrique Tria, E-mail: henriquetria@uol.com.br; Izar, Maria Cristina; Fonseca, Henrique Andrade; Póvoa, Rui Manuel [Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil); Saraiva, José Francisco [Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, SP (Brazil); Forti, Adriana [Centro de Diabetes e Hipertensão de Fortaleza, Fortaleza, CE (Brazil); Jardim, Paulo Cesar B. V. [Universidade Federal de Goiânia, Goiânia, GO (Brazil); Introcaso, Luis [Centro de Investigação Clínica de Brasília, Brasília, DF (Brazil); Yugar-Toledo, Juan [Escola de Medicina de São José do Rio Preto, São José do Rio Preto, SP (Brazil); Xavier, Hermes Tóros [Centro de Investigação Clínica de Santos, Santos, SP (Brazil); Universidade de São Paulo (USP), São Paulo, SP (Brazil); Faludi, André Arpad [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP (Brazil); Fonseca, Francisco A. H. [Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil)

    2014-10-15

    Patients with diabetes are in extract higher risk for fatal cardiovascular events. To evaluate major predictors of mortality in subjects with type 2 diabetes. A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality. After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017). Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.

  18. Photoprotective mechanism of the non-target organism Arabidopsis thaliana to paraquat exposure.

    Science.gov (United States)

    Moustaka, Julietta; Moustakas, Michael

    2014-05-01

    The response of photosystem II (PSII), of the non-target organism Arabidopsis thaliana, to paraquat (Pq) exposure was studied by chlorophyll fluorescence imaging. Effects of 1mM Pq application by spray on A. thaliana leaves were monitored as soon as 20min after application at the deposit areas of the droplets. A decline in the effective quantum yield of photochemical energy conversion in PSII (ΦPSII) was accompanied by an increase in the quantum yield for dissipation by down regulation in PSII (ΦNPQ). The concomitant decrease in the quantum yield of non-regulated energy loss in PSII (ΦNO) pointed out a quick effective photoprotection mechanism to Pq exposure. Even 1h after Pq spray, when the maximum Pq effect was observed, the decrease of electron transport rate (ETR) and the increase in non-photochemical quenching (NPQ) resulted to maintain almost the same redox state of quinone A (QA) as control plants. Thus, maximal photoprotection was achieved since NPQ was regulated in such a way that PSII reaction centers remained open. Arabidopsis plants were protected from Pq exposure, by increasing NPQ that dissipates light energy and decreases the efficiency of photochemical reactions of photosynthesis (down regulation of PSII) via the "water-water cycle". PSII photochemistry began to recover 4h after Pq exposure, and this was evident from the increase of ΦPSII, the simultaneous decrease of ΦNPQ, and the concomitant decrease of ΦNO. Yet, ETR began to increase, as well as the fraction of open PSII reaction centers. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    DEFF Research Database (Denmark)

    Ehret, Georg B; Ferreira, Teresa; Chasman, Daniel I

    2016-01-01

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66...... across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings...... expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation....

  20. Scientific Opinion on the assessment of potential impacts of genetically modified plants on non-target organisms

    DEFF Research Database (Denmark)

    Arpaia, Salvatore; Bartsch, Detlef; Delos, Marc

    The European Food Safety Authority (EFSA) asked the Panel on Genetically Modified Organisms to establish a self-tasking Working Group with the aim of (1) producing a scientific review of the current guidance of the GMO Panel for Environmental Risk Assessment (ERA), focusing on the potential impacts...... of GM plants on Non-Target Organisms (NTOs), (2) proposing criteria for NTOs selection, and (3) providing advise on standardized testing methodology. This initiative was undertaken in response to a need and request from a wide range of stakeholders, including the European Commission and Member States....... In first instance, the self-tasking Working Group on Non-Target Organisms (EFSA NTO WG) mainly considered impacts of GM plants on invertebrate species, but also took account of ecosystem functions that could be altered. The EFSA NTO WG considered the necessity for clear and objective protection goals...

  1. Analysis of the Possibility to Organize the Management Accounting through the Target Costing (TC Method in the Romanian Entities

    Directory of Open Access Journals (Sweden)

    Sorinel CĂPUŞNEANU

    2011-09-01

    Full Text Available This article presents a way of organizing the management accounting and cost calculation through the Target Costing method. There are treated the development stages of Target Costing method, and the role of the management accountant in the development and implementation of this method. The causes behind the choice to adapt the principles of Target Costing method to the Romanian General Accounting Plan and the operation of accounts used in highlighting economic and financial operations at the entity leve have been analyzedl. There are treated theoretical and applied the methodological steps taken in the management accounting and cost calculation. The article ends with the conclusions of the authors about the possibility of adapting the principles of Target Costing method to the Romanian General Accounting Plan and the advantages offered by this method.

  2. An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles.

    Science.gov (United States)

    Pramanik, Arindam; Laha, Dipranjan; Dash, Sandeep Kumar; Chattopadhyay, Sourav; Roy, Somenath; Das, Dipak Kumar; Pramanik, Panchanan; Karmakar, Parimal

    2016-11-01

    We have developed a strategy for targeted delivery of metal-diketo complex, "bis(2,4-pentanedionato) copper(II)" to breast cancer cells both in-vitro and in-vivo. This metal-organic complex induced ROS and subsequently DNA damage as well as mitochondrial membrane depolarization was observed. The mitochondria rupture further triggered apoptosis. For in-vitro targeting strategies, two different approaches were employed, folic acid or her-2 specific peptide (KCCYSL) was attached to stearic acid-modified polymeric Chitosan nanoparticles loaded with metal-organic complex "bis(2,4-pentanedionato)copper(II)". This was tested on two pairs of isogenic cells (FR+/FR- MCf-7 and her2+ /her2- MCF-7) and it was observed that cells expressing the receptor were susceptible to the drug whereas non-expressing isogenic cells were almost un-affected. During in-vivo studies, mice receiving targeted delivery of bis(2,4-pentanedionato) copper (II) had increased survivability and reduced tumor volume compared to non-targeted drug delivery. During toxicity studies for liver enzymes it was also found that the mice receiving targeted drug did not show any sign of liver damage as well as other histology changes. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Imbalanced mechanistic target of rapamycin C1 and C2 activity in the cerebellum of Angelman syndrome mice impairs motor function.

    Science.gov (United States)

    Sun, Jiandong; Liu, Yan; Moreno, Stephanie; Baudry, Michel; Bi, Xiaoning

    2015-03-18

    Angelman syndrome (AS) is a neurogenetic disorder caused by deficiency of maternally expressed ubiquitin-protein ligase E3A (UBE3A), an E3 ligase that targets specific proteins for proteasomal degradation. Although motor function impairment occurs in all patients with AS, very little research has been done to understand and treat it. The present study focuses on Ube3A deficiency-induced alterations in signaling through the mechanistic target of rapamycin (mTOR) pathway in the cerebellum of the AS mouse model and on potential therapeutic applications of rapamycin. Levels of tuberous sclerosis complex 2 (TSC2), a negative regulator of mTOR, were increased in AS mice compared with wild-type mice; however, TSC2 inhibitory phosphorylation was also increased. Correspondingly, levels of phosphorylated/active mTOR were increased. Phosphorylation of the mTORC1 substrates S6 kinase 1 (S6K1) and S6 was elevated, whereas that of the mTORC2 substrates AKT and N-myc downstream regulated 1 was decreased, suggesting enhanced mTORC1 but inhibited mTORC2 signaling. Semi-chronic treatment of AS mice with rapamycin not only improved their motor performance but also normalized mTORC1 and mTORC2 signaling. Furthermore, inhibitory phosphorylation of rictor, a key regulatory/structural subunit of the mTORC2 complex, was increased in AS mice and decreased after rapamycin treatment. These results indicate that Ube3A deficiency leads to overactivation of the mTORC1-S6K1 pathway, which in turn inhibits rictor, resulting in decreased mTORC2 signaling in Purkinje neurons of AS mice. Finally, rapamycin treatment also improved dendritic spine morphology in AS mice, through inhibiting mTORC1 and possibly enhancing mTORC2-mediated regulation of synaptic cytoskeletal elements. Collectively, our results indicate that the imbalance between mTORC1 and mTORC2 activity may contribute to synaptic pathology and motor impairment in AS. Copyright © 2015 the authors 0270-6474/15/354706-13$15.00/0.

  4. Pathogenicity Tests on Nine Mosquito Species and Several Non-target Organisms with Strelkovimermis spiculatus (Nemata Mermithidae)

    Science.gov (United States)

    Becnel, James J.; Johnson, Margaret A.

    1998-01-01

    Nine species of mosquitoes and several species of non-target aquatic organisms were tested for susceptibility to the mernaithid nematode, Strelkovimermis spiculatus. All species of Anopheles, Aedes, Culex, and Toxorhynchites exposed to S. spiculatus were susceptible. Of the nine mosquito species tested, C. pipiens quinquefasciatus had the greatest tolerance to initial invasion and the highest percent infection of those that survived. High levels of infection were also achieved with Aedes taeniorhynchus and A. albopictus, but these mosquitoes were significantly less tolerant to parasitism than C. pipiens quinquefasciatus. Strelkovimermis spiculatus did not infect or develop in any of the non-target hosts tested. PMID:19274233

  5. Comparison of the Absorbed Dose of Target Organs between Conventional and Digital Panoramic Radiography

    OpenAIRE

    Zohre Reyhani; Nadia Nil Avar; Mohamad Ali Moghadam

    2016-01-01

    The purpose of this study was to measure and compare target organ’s exposure by direct digital and conventional panoramic radiography. Dose measurements were carried out on a RANDO phantom, which TLDs were placed into 5 target area: thyroid gland, left and right submandibular and parotid salivary glands. Panoramic radiographs were taken with two conventional (CRANEX Tome, Soredex, Tusula Finland) and direct digital devices (CRANEX D, Soredex, Tusula Finland).In total, the phantom was ir...

  6. Active site-targeted covalent irreversible inhibitors of USP7 impair the functions of Foxp3+ T-regulatory cells by promoting ubiquitination of Tip60.

    Science.gov (United States)

    Wang, Feng; Wang, Liqing; Wu, Jian; Sokirniy, Ivan; Nguyen, Phuong; Bregnard, Thomas; Weinstock, Joseph; Mattern, Michael; Bezsonova, Irina; Hancock, Wayne W; Kumar, Suresh

    2017-01-01

    Accumulation of Foxp3+ T-regulatory (Treg) cells in the tumor microenvironment is associated with tumor immune evasion and poor patient outcome in the case of many solid tumors. Current therapeutic strategies for blocking Treg functions are not Treg-specific, and display only modest and transient efficacy. Recent studies revealed that ubiquitin-specific protease 7 (USP7) is essential for Treg functions by stabilizing expression of Tip60 and Foxp3, which together are central to the development and maintenance of the Treg cell lineage. Pharmacological inhibition of USP7 is therefore a promising strategy for suppressing Treg functions and promoting anti-tumor immunity. Previously, we reported the P5091 series of small molecule USP7 inhibitors and demonstrated their direct anti-tumor activity in vivo using xenograft models. However, the precise mechanism of action of these compounds was not well defined. In this study, we report the development and characterization of P217564, a second-generation USP7 inhibitor with improved potency and selectivity. P217564 selectively targets the catalytic cleft of USP7 and modifies its active site cysteine (C223) by forming a covalent adduct. Irreversible inhibition of USP7 results in durable downstream biological responses in cells, including down-regulation of Tip60 and consequent impairment of Treg suppressive function. In addition, we demonstrate that both USP7 and various USP7 substrates are subjected to Lys48-mediated ubiquitin modification, consistent with increased proteasomal degradation of these proteins because of USP7 inhibition.

  7. Correlation of insulin resistance extent with systemic inflammatory response and target organ damage in children with sepsis

    OpenAIRE

    Min Liu

    2017-01-01

    Objective: To explore the correlation of insulin resistance (IR) extent with systemic inflammatory response and target organ damage in children with sepsis. Methods: A total of 70 patients with sepsis who were treated in our hospital between June 2013 and July 2016 were collected as observation group, 50 healthy children who received vaccination in our hospital during the same period were selected as normal control group, the insulin resistance index (HOMA-IR) of two groups of ...

  8. A method for mapping tissue volume model onto target volume using volumetric self-organizing deformable model

    Science.gov (United States)

    Miyauchi, Shoko; Morooka, Ken'ichi; Tsuji, Tokuo; Miyagi, Yasushi; Fukuda, Takaichi; Kurazume, Ryo

    2016-03-01

    This paper proposes a new method for mapping volume models of human tissues onto a target volume with simple shapes. The proposed method is based on our modified self-organizing deformable model (mSDM)1, 2 which finds the one-to-one mapping with no foldovers between arbitrary surface model and a target surface. By extending mSDM to apply to volume models, the proposed method, called volumetric SDM (vSDM), establishes the one-to-one correspondence between the tissue volume model and its target volume. At the same time, vSDM can preserve geometrical properties of the original model before and after mapping. This characteristic of vSDM makes it easy to find the correspondence between tissue models.

  9. Development of a software for quantitative evaluation radiotherapy target and organ-at-risk segmentation comparison.

    Science.gov (United States)

    Kalpathy-Cramer, Jayashree; Awan, Musaddiq; Bedrick, Steven; Rasch, Coen R N; Rosenthal, David I; Fuller, Clifton D

    2014-02-01

    Modern radiotherapy requires accurate region of interest (ROI) inputs for plan optimization and delivery. Target delineation, however, remains operator-dependent and potentially serves as a major source of treatment delivery error. In order to optimize this critical, yet observer-driven process, a flexible web-based platform for individual and cooperative target delineation analysis and instruction was developed in order to meet the following unmet needs: (1) an open-source/open-access platform for automated/semiautomated quantitative interobserver and intraobserver ROI analysis and comparison, (2) a real-time interface for radiation oncology trainee online self-education in ROI definition, and (3) a source for pilot data to develop and validate quality metrics for institutional and cooperative group quality assurance efforts. The resultant software, Target Contour Testing/Instructional Computer Software (TaCTICS), developed using Ruby on Rails, has since been implemented and proven flexible, feasible, and useful in several distinct analytical and research applications.

  10. Hypertensive Target Organ Damage and Longitudinal Changes in Brain Structure and Function The Second Manifestations of Arterial Disease-Magnetic Resonance Study

    NARCIS (Netherlands)

    van der Veen, Pieternella H.; Geerlings, Mirjam I.|info:eu-repo/dai/nl/146382315; Visseren, Frank L. J.|info:eu-repo/dai/nl/166267678; Nathoe, Hendrik M.|info:eu-repo/dai/nl/267961472; Mali, Willem P T M|info:eu-repo/dai/nl/071107533; van der Graaf, Yolanda|info:eu-repo/dai/nl/072825847; Muller, Majon

    2015-01-01

    Hypertension has been related to structural and functional brain changes. In high-risk populations, hypertensive target organ damage might better represent exposure to high blood pressure than the blood pressure measurement itself. We examined the association of hypertensive target organ damage with

  11. Targeted impairment of thymidine kinase 2 expression in cells induces mitochondrial DNA depletion and reveals molecular mechanisms of compensation of mitochondrial respiratory activity

    Energy Technology Data Exchange (ETDEWEB)

    Villarroya, Joan, E-mail: joanvillarroya@gmail.com [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Institut de Recerca l' Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Lara, Mari-Carmen [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Department of Neurology, Columbia University Medical Center, New York, NY (United States); Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII (Spain); Dorado, Beatriz [Department of Neurology, Columbia University Medical Center, New York, NY (United States); Garrido, Marta [Unitat de Biologia Cel.lular i Molecular, IMIM-Hospital del Mar, Barcelona (Spain); Garcia-Arumi, Elena [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), ISCIII (Spain); Meseguer, Anna [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain); Hirano, Michio [Department of Neurology, Columbia University Medical Center, New York, NY (United States); Vila, Maya R. [Institut de Recerca, Hospital Universitari de la Vall d' Hebron, Barcelona (Spain)

    2011-04-08

    Highlights: {yields} We impaired TK2 expression in Ost TK1{sup -} cells via siRNA-mediated interference (TK2{sup -}). {yields} TK2 impairment caused severe mitochondrial DNA (mtDNA) depletion in quiescent cells. {yields} Despite mtDNA depletion, TK2{sup -} cells show high cytochrome oxidase activity. {yields} Depletion of mtDNA occurs without imbalance in the mitochondrial dNTP pool. {yields} Nuclear-encoded ENT1, DNA-pol {gamma}, TFAM and TP gene expression is lowered in TK2{sup -} cells. -- Abstract: The mitochondrial DNA (mtDNA) depletion syndrome comprises a clinically heterogeneous group of diseases characterized by reductions of the mtDNA abundance, without associated point mutations or rearrangements. We have developed the first in vitro model to study of mtDNA depletion due to reduced mitochondrial thymidine kinase 2 gene (TK2) expression in order to understand the molecular mechanisms involved in mtDNA depletion syndrome due to TK2 mutations. Small interfering RNA targeting TK2 mRNA was used to decrease TK2 expression in Ost TK1{sup -} cells, a cell line devoid of endogenous thymidine kinase 1 (TK1). Stable TK2-deficient cell lines showed a reduction of TK2 levels close to 80%. In quiescent conditions, TK2-deficient cells showed severe mtDNA depletion, also close to 80% the control levels. However, TK2-deficient clones showed increased cytochrome c oxidase activity, higher cytochrome c oxidase subunit I transcript levels and higher subunit II protein expression respect to control cells. No alterations of the deoxynucleotide pools were found, whereas a reduction in the expression of genes involved in nucleoside/nucleotide homeostasis (human equilibrative nucleoside transporter 1, thymidine phosphorylase) and mtDNA maintenance (DNA-polymerase {gamma}, mitochondrial transcription factor A) was observed. Our findings highlight the importance of cellular compensatory mechanisms that enhance the expression of respiratory components to ensure respiratory activity

  12. Structure and organization of drug-target networks: insights from genomic approaches for drug discovery.

    Science.gov (United States)

    Janga, Sarath Chandra; Tzakos, Andreas

    2009-12-01

    Recent years have seen an explosion in the amount of "omics" data and the integration of several disciplines, which has influenced all areas of life sciences including that of drug discovery. Several lines of evidence now suggest that the traditional notion of "one drug-one protein" for one disease does not hold any more and that treatment for most complex diseases can best be attempted using polypharmacological approaches. In this review, we formalize the definition of a drug-target network by decomposing it into drug, target and disease spaces and provide an overview of our understanding in recent years about its structure and organizational principles. We discuss advances made in developing promiscuous drugs following the paradigm of polypharmacology and reveal their advantages over traditional drugs for targeting diseases such as cancer. We suggest that drug-target networks can be decomposed to be studied at a variety of levels and argue that such network-based approaches have important implications in understanding disease phenotypes and in accelerating drug discovery. We also discuss the potential and scope network pharmacology promises in harnessing the vast amount of data from high-throughput approaches for therapeutic advantage.

  13. Development of a Software for Quantitative Evaluation Radiotherapy Target and Organ-at-Risk Segmentation Comparison

    NARCIS (Netherlands)

    Kalpathy-Cramer, Jayashree; Awan, Musaddiq; Bedrick, Steven; Rasch, Coen R. N.; Rosenthal, David I.; Fuller, Clifton D.

    2014-01-01

    Modern radiotherapy requires accurate region of interest (ROI) inputs for plan optimization and delivery. Target delineation, however, remains operator-dependent and potentially serves as a major source of treatment delivery error. In order to optimize this critical, yet observer-driven process, a

  14. Organic Over-the-Horizon Targeting for the 2025 Surface Fleet

    Science.gov (United States)

    2015-06-01

    System -Investing time and money into a system that cannot evolve with a changing threat -Having a system that is unable to function in an A2...individual surface combatant in the prosecution of an OTH target, exogenous assets will not be part of SEA-21A SoS design recommendation to address the

  15. New investigations of organic compounds for targets with polarized hydrogen nuclei

    Science.gov (United States)

    Bunyatova, E. I.

    1995-02-01

    Pentanol C 5H 12O, polyethylene (CH 2) n and their deuterated analogues C 5D 12O and (CD 2) n are proposed as target materials. Particular attention is paid to the production of materials in a glass-like (amorphous) state.

  16. New investigations of organic compounds for targets with polarized hydrogen nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Bunyatova, E.I. [Joint Inst. for Nuclear Research, Dubna (Russian Federation)

    1995-03-01

    Pentanol C{sub 5}H{sub 12}O, polyethylene (CH{sub 2}){sub n} and their deuterated analogues C{sub 5}D{sub 12}O and (CD{sub 2}){sub n} are proposed as target materials. Particular attention is paid to the production of materials in a glass-like (amorphous) state. ((orig.))

  17. Emission spectroscopy of hypervelocity impacts on aluminum, organic and high-explosive targets

    NARCIS (Netherlands)

    Verreault, J.; Day, J.P.R.; Halswijk, W.H.C.; Loiseau, J.; Huneault, J.; Higgins, A.J.; Devir, A.D.

    2015-01-01

    Laboratory experiments of hypervelocity impacts on aluminum, nylon and high-explosive targets are presented. Spectral measurements of the impact flash are recorded, together with radiometric measurements to derive the temperature of the flash. Such experiments aim at demonstrating that the impact

  18. Functionalization of Self-Organized Nanoparticles for Biological Targeting and Active Drug Release

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming

    Functional nanomaterials have attracted much attention due to the unique properties of these nanoconstructs. In recognition of the huge potential within this field, much research has been devoted to develop sophisticated nanoparticles for medical diagnostics, sensors, contrast agents, vaccines...... at the surface of the nanoconstructs, resulting in anionic nanoparticles with long circulation properties in xenograft HT1080 tumor‐bearing mice. Charge reversal by peptide hydrolysis was achieved in the presence of proteases, resulting in cationic particles which were readily internalized by cells in vitro...... of functionalized liposomes were slower than the solution phase counterpart and often far from quantitative. The effect of active targeting with 64Cu octreotate liposomes targeting the somatostatin receptor 2 was evaluated to improve tumor bioimaging for diagnostic applications, using positron emission tomography...

  19. Evolution-based strategy to generate non-genetically modified organisms Saccharomyces cerevisiae strains impaired in sulfate assimilation pathway.

    Science.gov (United States)

    De Vero, L; Solieri, L; Giudici, P

    2011-11-01

    An evolution-based strategy was designed to screen novel yeast strains impaired in sulfate assimilation. Specifically, molybdate and chromate resistance was used as selectable phenotype to select sulfate permease-deficient variants that unable to produce sulfites and hydrogen sulfide (H(2) S). Four Saccharomyces cerevisiae parent strains were induced to sporulate. After tetrad digestion, spore suspensions were observed under the microscope to monitor the conjugation of gametes. Then, the cell suspension was inoculated in tubes containing YPD medium supplemented with ammonium molybdate or potassium chromate. Forty-four resistant strains were obtained and then tested in microvinifications. Three strains with a low sulfite production (SO2 < 10 mg l(-1)) and with an impaired H2S production in grape must without added sulfites were selected. Our strategy enabled the selection of improved yeasts with desired oenological characteristics. Particularly, resistance to toxic analogues of sulfate allowed us to detect strains that unable to assimilate sulfates. This strategy that combines the sexual recombination of spores and application of a specific selective pressure provides a rapid screening method to generate genetic variants and select improved wine yeast strains with an impaired metabolism regarding the production of sulfites and H2S. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

  20. Radiolabeled white blood cells and direct targeting of micro-organisms for infection imaging

    International Nuclear Information System (INIS)

    Kumar, V.

    2005-01-01

    Infection imaging is complicated due to multitude of factors interfering with the design of radiopharmaceuticals. More than 3 decades ago, labeled leukocytes have been introduced for infection imaging and new radiopharmaceuticals have been emerging on regular basis. However, labeled leukocytes by in vivo and in vitro methods are very effective for diagnosing various lesions such as osteomyelitis, cellulitis, diabetic foot, Crohn's disease, inflammatory bowel disease and in distinguishing prosthetic infection from loosening of prosthesis. But in vitro labeling method using 1 11I n-oxine, 9 9mT c-HMPAO or 9 9mT c-stannous colloid have the inherent limitation of personnel safety risks of infection and cross contamination. To overcome these problems, attempts have been made to directly target leukocytes by in vivo labeling techniques. There are several receptors present on the leukocytes and the granulocytes, which can be targeted with suitable ligands. These will include anti-NCA90-Fab, murine MoAb IgG 1 that is cross-reactive to antigen 95 on neutrophils, anti-CD15 antigen and DPC-11870 that targets the leukotriene B4 receptors of granulocytes. In a new approach, 9 9mT c-labeled ciprofloxacin has been developed to directly target live bacteria to detect infection by in vivo method. This approach showed considerable promise in the preliminary studies but clinical trials showed limitations. Analogs of a natural mammalian antimicrobial agents, such as Ubiquicidin were successful in animal studies and have now entered clinical trials. 9 9mT c-labeled fluconazole (a fungal antibiotic) and labeled Chitinase (1 23I -ChiB E144Q), have been developed to detect fungal infection. The ability to distinguish between fungal and bacterial infection is considered important, as patients undergoing chemotherapy are prone to fungal infection. Undoubtedly, the new trends and new radiopharmaceuticals developed for infection and inflammation imaging have contributed towards a better

  1. Organically modified silica nanoparticles are biocompatible and can be targeted to neurons in vivo.

    Directory of Open Access Journals (Sweden)

    Farda Barandeh

    Full Text Available The application of nanotechnology in biological research is beginning to have a major impact leading to the development of new types of tools for human health. One focus of nanobiotechnology is the development of nanoparticle-based formulations for use in drug or gene delivery systems. However most of the nano probes currently in use have varying levels of toxicity in cells or whole organisms and therefore are not suitable for in vivo application or long-term use. Here we test the potential of a novel silica based nanoparticle (organically modified silica, ORMOSIL in living neurons within a whole organism. We show that feeding ORMOSIL nanoparticles to Drosophila has no effect on viability. ORMOSIL nanoparticles penetrate into living brains, neuronal cell bodies and axonal projections. In the neuronal cell body, nanoparticles are present in the cytoplasm, but not in the nucleus. Strikingly, incorporation of ORMOSIL nanoparticles into the brain did not induce aberrant neuronal death or interfered with normal neuronal processes. Our results in Drosophila indicate that these novel silica based nanoparticles are biocompatible and not toxic to whole organisms, and has potential for the development of long-term applications.

  2. Organically Modified Silica Nanoparticles Are Biocompatible and Can Be Targeted to Neurons In Vivo

    Science.gov (United States)

    Kumar, Rajiv; Iacobucci, Gary J.; Kuznicki, Michelle L.; Kosterman, Andrew; Bergey, Earl J.; Prasad, Paras N.; Gunawardena, Shermali

    2012-01-01

    The application of nanotechnology in biological research is beginning to have a major impact leading to the development of new types of tools for human health. One focus of nanobiotechnology is the development of nanoparticle-based formulations for use in drug or gene delivery systems. However most of the nano probes currently in use have varying levels of toxicity in cells or whole organisms and therefore are not suitable for in vivo application or long-term use. Here we test the potential of a novel silica based nanoparticle (organically modified silica, ORMOSIL) in living neurons within a whole organism. We show that feeding ORMOSIL nanoparticles to Drosophila has no effect on viability. ORMOSIL nanoparticles penetrate into living brains, neuronal cell bodies and axonal projections. In the neuronal cell body, nanoparticles are present in the cytoplasm, but not in the nucleus. Strikingly, incorporation of ORMOSIL nanoparticles into the brain did not induce aberrant neuronal death or interfered with normal neuronal processes. Our results in Drosophila indicate that these novel silica based nanoparticles are biocompatible and not toxic to whole organisms, and has potential for the development of long-term applications. PMID:22238611

  3. Comparable Educational Benefits in Half the Time: An Alternating Organic Chemistry Laboratory Sequence Targeting Prehealth Students

    Science.gov (United States)

    Young, Sherri C.; Colabroy, Keri L.; Baar, Marsha R.

    2016-01-01

    The laboratory is a mainstay in STEM education, promoting the development of critical thinking skills, dexterity, and scientific curiosity. The goals in the laboratory for nonchemistry, prehealth majors, though, could be distinguished from those for chemistry majors. In service courses such as organic chemistry, much laboratory time is often spent…

  4. Collective Punishment Depends on Collective Responsibility and Political Organization of the Target Group

    NARCIS (Netherlands)

    Pereira, A.; Berent, J.; Falomir-Pichastor, J.M.; Staerklé, C.; Butera, F.

    2015-01-01

    What factors determine the willingness to inflict collective punishment upon a group for a misdeed committed by individual group members? This research investigates the effect of collective responsibility shared among group members and the moderating effect of the group's political organization

  5. Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.

    Science.gov (United States)

    Ishizaki, Jun; Takemori, Ayako; Suemori, Koichiro; Matsumoto, Takuya; Akita, Yoko; Sada, Ken-Ei; Yuzawa, Yukio; Amano, Koichi; Takasaki, Yoshinari; Harigai, Masayoshi; Arimura, Yoshihiro; Makino, Hirofumi; Yasukawa, Masaki; Takemori, Nobuaki; Hasegawa, Hitoshi

    2017-09-29

    Targeted proteomics, which involves quantitative analysis of targeted proteins using selected reaction monitoring (SRM) mass spectrometry, has emerged as a new methodology for discovery of clinical biomarkers. In this study, we used targeted serum proteomics to identify circulating biomarkers for prediction of disease activity and organ involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A large-scale SRM assay targeting 135 biomarker candidates was established using a triple-quadrupole mass spectrometer coupled with nanoflow liquid chromatography. Target proteins in serum samples from patients in the active and remission (6 months after treatment) stages were quantified using the established assays. Identified marker candidates were further validated by enzyme-linked immunosorbent assay using serum samples (n = 169) collected in a large-cohort Japanese study (the RemIT-JAV-RPGN study). Our proteomic analysis identified the following proteins as biomarkers for discriminating patients with highly active AAV from those in remission or healthy control subjects: tenascin C (TNC), C-reactive protein (CRP), tissue inhibitor of metalloproteinase 1 (TIMP1), leucine-rich alpha-2-glycoprotein 1, S100A8/A9, CD93, matrix metalloproteinase 9, and transketolase (TKT). Of these, TIMP1 was the best-performing marker of disease activity, allowing distinction between mildly active AAV and remission. Moreover, in contrast to CRP, serum levels of TIMP1 in patients with active AAV were significantly higher than those in patients with infectious diseases. The serum levels of TKT and CD93 were higher in patients with renal involvement than in those without, and they predicted kidney outcome. The level of circulating TNC was elevated significantly in patients with lung infiltration. AAV severity was associated with markers reflecting organ involvement (TKT, CD93, and TNC) rather than inflammation. The eight markers and myeloperoxidase (MPO

  6. Personalized Therapy Against Preeclampsia by Replenishing Placental Protein 13 (PP13 Targeted to Patients With Impaired PP13 Molecule or Function

    Directory of Open Access Journals (Sweden)

    Hamutal Meiri

    Full Text Available Hypertensive disorders affect about one third of all people aged 20 and above, and are treated with anti-hypertensive drugs. Preeclampsia (PE is one form of such disorders that only develops during pregnancy. It affects ten million pregnant women globally and additionally causes fetal loss and major newborn disabilities. The syndrome's origin is multifactorial, and anti-hypertensive drugs are ineffective in treating it. Biomarkers are helpful for predict its development. Generic drugs, such as low dose aspirin, were proven effective in preventing preterm PE. However, it does not cure the majority of cases and many studies are underway for fighting PE with extended use of additional generic drugs, or through new drug development programs.This review focuses on placental protein 13 (PP13. This protein is only expressed in the placenta. Impaired PP13 DNA structure and/or its reduced mRNA expression leads to lower blood PP13 level that predict a higher risk of developing PE. Two polymorphic PP13 variants have been identified: (1 The promoter PP13 variant with an “A/A” genotype in the -98 position (versus “A/C” or “C/C”. Having the “A/A” genotype is coupled to lower PP13 expression, mainly during placental syncytiotrophoblast differentiation and, if associated with obesity and history of previous preeclampsia, it accurately predicts higher risk for developing the disorder. (2 A thymidine deletion at position 221 causes a frame shift in the open reading frame, and the formation of an early stop codon resulting in the formation of DelT221, a truncated variant of PP13. In pregnant rodents, both short- and long- term replenishment of PP13 causes reversible hypotension and vasodilation of uterine vessels. Long-term exposure is also accompanied by the development of larger placentas and newborns. Also, only w/t PP13 is capable of inducing leukocyte apoptosis, providing maternal immune tolerance to pregnancy.Based on published data, we

  7. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    Science.gov (United States)

    Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A.; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J.P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arking, Dan E.; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Inês; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S.; Chung, Ren-Hua; Collins, Francis S.; Connell, John M.; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S.F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F.; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H. Franco; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H.; Goodarzi, Mark O.; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven C.; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R.; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N William N.W.R.; Renström, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H.-H.; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M.; van Iperen, Erik P.A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njølstad, Inger; Schwarz, Peter EH.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H.-Erich; Palmer, Colin N.A.; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J.F.; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

    2016-01-01

    To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation. PMID:27618452

  8. Self-organized nanoparticles based on chitosan-folic acid and dextran succinate-doxorubicin conjugates for drug targeting.

    Science.gov (United States)

    Lee, Kyung Dong; Choi, Seon-Hee; Kim, Da Hye; Lee, Hye-Young; Choi, Ki-Choon

    2014-12-01

    Folic acid-decorated self-organized nanoparticles were fabricated to target folate receptor of cancer cells. Doxorubicin (DOX) was conjugated with carboxyl group of dextran backbone using succinic anhydride (DexSU-DOX). DOX-loaded self-organized nanoparticles were prepared by complexation with folic acid-grafted chitosan (ChitoFA) and DexSU-DOX. Nanoparticles in the aqueous environment have spherical shapes with average size less than 100 nm and their sizes were increased by coated with ChitoPEG or ChitoFA. At cell culture study with KB cells, ChitoFA coated nanoparticles (FADex NP) revealed folate-receptor mediated endocytosis to cancer cells and cell viability was significantly changed by folate receptor targeting. Tumor xenograft model of KB cells also showed similar results, i.e. FAdex NP efficiently inhibited growth of tumor compared to the treatment group with blocking of folate receptor. These results indicated that DOX-loaded nanoparticles of FADex NP are promising vehicle for anticancer drug targeting.

  9. Prevalence and causes of visual impairment according to World Health Organization and United States criteria in an aged, urban Scandinavian population

    DEFF Research Database (Denmark)

    Buch, Helena; Vinding, T; Nielsen, N V

    2001-01-01

    eligible persons, 946 (96.9%) could be examined. Information about best-corrected visual acuity (VA) was obtained from 944 cooperative persons (96.7%). METHODS: Data from the Copenhagen City Eye Study were used to assess the cause-specific prevalence of visual impairment as defined by the World Health...... Organization (WHO) (VA worse than 20/60-20/400 in the better eye) and the criteria used most commonly in the United States (VA worse than 20/40 but better than 20/200 in the better eye). Eligible subjects underwent an extensive ophthalmologic examination at The National University Hospital of Denmark. MAIN...

  10. Organ-specific shifts in mtDNA heteroplasmy following systemic delivery of a mitochondria-targeted restriction endonuclease.

    Science.gov (United States)

    Bacman, S R; Williams, S L; Garcia, S; Moraes, C T

    2010-06-01

    Most pathogenic mtDNA mutations are heteroplasmic and there is a clear correlation between high levels of mutated mtDNA in a tissue and pathology. We have found that in vivo double-strand breaks (DSBs) in mtDNA lead to digestion of cleaved mtDNA and replication of residual mtDNA. Therefore, if DSB could be targeted to mutations in mtDNA, mutant genomes could be eliminated and the wild-type mtDNA would repopulate the cells. This can be achieved by using mitochondria-targeted restriction endonucleases as a means to degrade specific mtDNA haplotypes in heteroplasmic cells or tissues. In this work, we investigated the potential of systemic delivery of mitochondria-targeted restriction endonucleases to reduce the proportion of mutant mtDNA in specific tissues. Using the asymptomatic NZB/BALB mtDNA heteroplasmic mouse as a model, we found that a mitochondria-targeted ApaLI (that cleaves BALB mtDNA at a single site and does not cleave NZB mtDNA) increased the proportion of NZB mtDNA in target tissues. This was observed in heart, using a cardiotropic adeno-associated virus type-6 (AAV6) and in liver, using the hepatotropic adenovirus type-5 (Ad5). No mtDNA depletion or loss of cytochrome c oxidase activity was observed in any of these tissues. These results show the potential of systemic delivery of viral vectors to specific organs for the therapeutic application of mitochondria-targeted restriction enzymes in mtDNA disorders.

  11. Cisplatin and oxaliplatin are toxic to cochlear outer hair cells and both target thioredoxin reductase in organ of Corti cultures.

    Science.gov (United States)

    Dammeyer, Pascal; Hellberg, Victoria; Wallin, Inger; Laurell, Göran; Shoshan, Maria; Ehrsson, Hans; Arnér, Elias S J; Kirkegaard, Mette

    2014-05-01

    Inhibition of thioredoxin reductase (TrxR) may be a contributing factor in cisplatin-induced ototoxicity. Direct exposure of organ of Corti to cisplatin and oxaliplatin gives equal loss of hair cells. Platinum-containing drugs are known to target the anti-oxidant selenoprotein TrxR in cancer cells. Two such anti-cancer, platinum-containing drugs, cisplatin and oxaliplatin, have different side effects. Only cisplatin induces hearing loss, i.e. has an ototoxic side effect that is not seen after treatment with oxaliplatin. The objective of this study was to evaluate if TrxR is a target in the cochlea. Loss of outer hair cells was also compared when cisplatin and oxaliplatin were administered directly to the organ of Corti. Organ of Corti cell culture was used for direct exposure to cisplatin and oxaliplatin. Hair cells were evaluated and the level of TrxR was assessed. Immunohistochemical staining for TrxR was performed. An animal model was used to evaluate the effect on TrxR after treatment with cisplatin and oxaliplatin in vivo. Direct exposure of cochlear organotypic cultures to either cisplatin or oxaliplatin induced comparable levels of outer hair cell loss and inhibition of TrxR, demonstrating that both drugs are similarly ototoxic provided that the cochlea becomes directly exposed.

  12. Prevalence and causes of visual impairment according to World Health Organization and United States criteria in an aged, urban Scandinavian population

    DEFF Research Database (Denmark)

    Buch, Helena; Vinding, T; Nielsen, N V

    2001-01-01

    Organization (WHO) (VA worse than 20/60-20/400 in the better eye) and the criteria used most commonly in the United States (VA worse than 20/40 but better than 20/200 in the better eye). Eligible subjects underwent an extensive ophthalmologic examination at The National University Hospital of Denmark. MAIN...... OUTCOME MEASURES: Best-corrected VA and primary causes of visual impairment. RESULTS: The prevalence of low vision according to the WHO definition ranged from 2.6% in subjects aged 70 to 74 years to 4.8% in subjects 75 to 80 years of age, with an age-adjusted relative prevalence of 1.58%. Using the U.......S. definition, the overall age-adjusted prevalence of visual impairment was 2.9%. The causes of visual impairment according to the WHO criteria were age-related macular degeneration (AMD) (44.4%), cataract (33.3%), glaucoma in combination with cataract (11.1%), myopic macular degeneration (5.6%), and diabetic...

  13. Impact of Demographics, Organ Impairment, Disease, Formulation, and Food on the Pharmacokinetics of the Selective S1P1 Receptor Modulator Ponesimod Based on 13 Clinical Studies.

    Science.gov (United States)

    Lott, Dominik; Lehr, Thorsten; Dingemanse, Jasper; Krause, Andreas

    2017-04-01

    Ponesimod is a selective, orally active sphingosine-1-phosphate receptor 1 modulator currently undergoing clinical evaluation for the treatment of multiple sclerosis (MS) in phase III clinical trials. Ponesimod dose-dependently reduces peripheral blood lymphocyte counts by blocking the egress of lymphocytes from lymphoid organs. A population pharmacokinetic (PK) analysis was performed based on pooled data from 13 clinical studies. Interindividual variability (IIV) and the impact of key demographic variables and other covariates on ponesimod exposure were assessed quantitatively. A two-compartment model with sequential zero/first-order absorption, including lag time, intercompartmental drug flow, and first-order clearance, adequately described the PK of ponesimod. Body weight, race, MS, psoriasis, hepatic impairment, drug formulation, and food were identified to significantly affect the concentration-time profile. The inclusion of these covariates into the model explained approximately 25 % of the IIV in the PK of ponesimod. Model predictions indicated that the impact of the identified covariates on ponesimod steady-state exposure is within 20 % of exposure, and thus within the margins of the IIV, with the exception of hepatic impairment. Changes up to threefold were predicted for severe cases of liver dysfunction. The rich data set enabled building a comprehensive population PK model that accurately predicts the concentration-time data of ponesimod. Covariates other than hepatic impairment were considered not clinically relevant and thus do not require dose adjustment. A potential dose adaptation can be conducted based on the final model.

  14. Na+,K+-ATPase as the Target Enzyme for Organic and Inorganic Compounds

    Directory of Open Access Journals (Sweden)

    Tatjana Momić

    2008-12-01

    Full Text Available This paper gives an overview of the literature data concerning specific and non specific inhibitors of Na+,K+-ATPase receptor. The immobilization approaches developed to improve the rather low time and temperature stability of Na+,K+-ATPase, as well to preserve the enzyme properties were overviewed. The functional immobilization of Na+,K+-ATPase receptor as the target, with preservation of the full functional protein activity and access of various substances to an optimum number of binding sites under controlled conditions in the combination with high sensitive technology for the detection of enzyme activity is the basis for application of this enzyme in medical, pharmaceutical and environmental research.

  15. Development and validation of a 48-target analytical method for high-throughput monitoring of genetically modified organisms.

    Science.gov (United States)

    Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

    2015-01-05

    The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection.

  16. Development and Validation of A 48-Target Analytical Method for High-throughput Monitoring of Genetically Modified Organisms

    Science.gov (United States)

    Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

    2015-01-01

    The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection. PMID:25556930

  17. Development of a qualitative real-time PCR method to detect 19 targets for identification of genetically modified organisms.

    Science.gov (United States)

    Peng, Cheng; Wang, Pengfei; Xu, Xiaoli; Wang, Xiaofu; Wei, Wei; Chen, Xiaoyun; Xu, Junfeng

    2016-01-01

    As the amount of commercially available genetically modified organisms (GMOs) grows recent years, the diversity of target sequences for molecular detection techniques are eagerly needed. Considered as the gold standard for GMO analysis, the real-time PCR technology was optimized to produce a high-throughput GMO screening method. With this method we can detect 19 transgenic targets. The specificity of the assays was demonstrated to be 100 % by the specific amplification of DNA derived from reference material from 20 genetically modified crops and 4 non modified crops. Furthermore, most assays showed a very sensitive detection, reaching the limit of ten copies. The 19 assays are the most frequently used genetic elements present in GM crops and theoretically enable the screening of the known GMO described in Chinese markets. Easy to use, fast and cost efficient, this method approach fits the purpose of GMO testing laboratories.

  18. Association of target organ damage with 24-hour systolic and diastolic blood pressure levels and hypertension subtypes in untreated Chinese.

    Science.gov (United States)

    Wei, Fang-Fei; Li, Yan; Zhang, Lu; Xu, Ting-Yan; Ding, Feng-Hua; Staessen, Jan A; Wang, Ji-Guang

    2014-02-01

    The association of target organ damage with 24-hour systolic and diastolic blood pressure levels and ambulatory hypertension subtypes has not yet been examined in untreated Chinese patients. We measured left ventricular mass index by echocardiography (n=619), the urinary albumin:creatinine ratio (n=1047), and aortic pulse wave velocity by tonometry (n=1013) in 1047 untreated subjects (mean age, 50.6 years; 48.9% women). Normotension was a 24-hour systolic/diastolic blood pressure Hypertension subtypes were isolated diastolic hypertension and mixed systolic plus diastolic hypertension. We assessed associations of interest by multivariable-adjusted linear models. Using normotension as reference, mixed hypertension was associated with higher (P≤0.003) left ventricular mass index (+4.31 g/m(2)), urinary albumin:creatinine ratio (+1.63 mg/mmol), and pulse wave velocity (+0.76 m/s); and isolated diastolic hypertension was associated with similar left ventricular mass index and pulse wave velocity (P≥0.39), but higher urinary albumin:creatinine ratio (+1.24 mg/mmol; P=0.002). In younger participants (blood pressure were +3.31/-0.36 g/m(2) (P=0.009/0.79) for left ventricular mass index, +1.15/+1.14 mg/mmol (P=0.02/0.04) for the urinary albumin:creatinine ratio, and +0.54/-0.05 m/s (Pblood pressure and mixed hypertension are major determinants of target organ damage irrespective of age and target organ, whereas 24-hour diastolic blood pressure and isolated diastolic hypertension only relate to the urinary albumin:creatinine ratio below middle age.

  19. Temperature Shift Experiments Suggest That Metabolic Impairment and Enhanced Rates of Photorespiration Decrease Organic Acid Levels in Soybean Leaflets Exposed to Supra-Optimal Growth Temperatures

    Directory of Open Access Journals (Sweden)

    Richard C. Sicher

    2015-08-01

    Full Text Available Elevated growth temperatures are known to affect foliar organic acid concentrations in various plant species. In the current study, citrate, malate, malonate, fumarate and succinate decreased 40 to 80% in soybean leaflets when plants were grown continuously in controlled environment chambers at 36/28 compared to 28/20 °C. Temperature effects on the above mentioned organic acids were partially reversed three days after plants were transferred among optimal and supra-optimal growth temperatures. In addition, CO2 enrichment increased foliar malate, malonate and fumarate concentrations in the supra-optimal temperature treatment, thereby mitigating effects of high temperature on respiratory metabolism. Glycerate, which functions in the photorespiratory pathway, decreased in response to CO2 enrichment at both growth temperatures. The above findings suggested that diminished levels of organic acids in soybean leaflets upon exposure to high growth temperatures were attributable to metabolic impairment and to changes of photorespiratory flux. Leaf development rates differed among temperature and CO2 treatments, which affected foliar organic acid levels. Additionally, we report that large decreases of foliar organic acids in response to elevated growth temperatures were observed in legume species.

  20. Visual Impairment

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Visual Impairment KidsHealth / For Teens / Visual Impairment What's in ... with the brain, making vision impossible. What Is Visual Impairment? Many people have some type of visual ...

  1. Characteristic clinical features of adipsic hypernatremia patients with subfornical organ-targeting antibody

    Science.gov (United States)

    Nakamura-Utsunomiya, Akari; Hiyama, Takeshi Y.; Okada, Satoshi; Noda, Masaharu; Kobayashi, Masao

    2017-01-01

    Abstract. Adipsic hypernatremia is a rare disease presenting as persistent hypernatremia with disturbance of thirst regulation and hypothalamic dysfunction. As a result of congenital disease, tumors, or inflammation, most cases are accompanied by structural abnormalities in the hypothalamic-pituitary area. While cases with no hypothalamic-pituitary structural lesion have been reported, their etiology has not been elucidated. Recently, we reported three patients with adipsic hypernatremia whose serum-derived immunoglobulin (Ig) specifically reacted with mouse subfornical organ (SFO) tissue. As one of the circumventricular organs (CVOs) that form a sensory interface between the blood and brain, the SFO is a critical site for generating physiological responses to dehydration and hypernatremia. Intravenous injection of the patient’s Ig fraction induced hypernatremia in mice, along with inflammation and apoptosis in the SFO. These results support a new autoimmunity-related mechanism for inducing adipsic hypernatremia without demonstrable hypothalamic-pituitary structural lesions. In this review, we aim to highlight the characteristic clinical features of these patients, in addition to etiological mechanisms related to SFO function. These findings may be useful for diagnosing adipsic hypernatremia caused by an autoimmune response to the SFO, and support development of new strategies for prevention and treatment. PMID:29026268

  2. Targeted binding of the M13 bacteriophage to thiamethoxam organic crystals.

    Science.gov (United States)

    Cho, Whirang; Fowler, Jeffrey D; Furst, Eric M

    2012-04-10

    Phage display screening with a combinatorial library was used to identify M13-type bacteriophages that express peptides with selective binding to organic crystals of thiamethoxam. The six most strongly binding phages exhibit at least 1000 times the binding affinity of wild-type M13 and express heptapeptide sequences that are rich in hydrophobic, hydrogen-bonding amino acids and proline. Among the peptide sequences identified, M13 displaying the pIII domain heptapeptide ASTLPKA exhibits the strongest binding to thiamethoxam in competitive binding assays. Electron and confocal microscopy confirm the specific binding affinity of ASTLPKA to thiamethoxam. Using atomic force microscope (AFM) probes functionalized with ASTLPKA expressing phage, we found that the average adhesion force between the bacteriophage and a thiamethoxam surface is 1.47 ± 0.80 nN whereas the adhesion force of wild-type M13KE phage is 0.18 ± 0.07 nN. Such a strongly binding bacteriophage could be used to modify the surface chemistry of thiamethoxam crystals and other organic solids with a high degree of specificity. © 2012 American Chemical Society

  3. CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ARTERIAL HYPERTENSION: VASCULAR WALL AS THE TARGET ORGAN IN COMORBID PATIENTS

    Directory of Open Access Journals (Sweden)

    N. A. Karoli

    2017-01-01

    Full Text Available Studies of endothelial dysfunction in patients with respiratory diseases have become relevant in recent years. Perhaps endothelial dysfunction and high arterial stiffness bind bronchopulmonary and cardiovascular diseases.Aim. To reveal features of disturbances of arterial wall vasoregulatory function in patients with chronic obstructive pulmonary disease (COPD in the presence and absence of arterial hypertension (HT.Material and methods. The study included 50 patients with COPD with normal blood pressure (BP and 85 patients with COPD and HT. Control group was presented by 20 practically healthy men comparable in age with COPD patients. Tests with reactive hyperemia (endothelium-dependent dilation and nitroglycerin (endothelium-independent dilation were performed in order to evaluate endothelium function. The number of desquamated endotheliocytes in the blood was determined.Results. In patients with COPD and HT in comparison with COPD patients without HT and healthy individuals more pronounced damages of the vascular wall, endothelium vasoregulatory function disturbances and a tendency to the reduction in endothelium-dependent vasodilation were determined both during COPD exacerbation and remission. These differences were most pronounced during the COPD exacerbation. In patients with COPD and HT in comparison with COPD patients without HT the damage of the vascular wall was more pronounced during the remission and endothelium-dependent dilatation disorder – during the exacerbation. The revealed disorders in patients with COPD and HT were associated with smoking status (r=0.61, p<0.01, severity of bronchial obstruction (r=-0.49, p<0.05, and hypoxemia (r=-0.76, p<0.01. We noted relationships between the parameters of 24-hour BP monitoring and remodeling of the brachial artery (r=0.34, p<0.05, endothelium lesion (r=0.25, p<0.05, and impairment of its vasoregulating function (r=-0.58, p<0.05. At that, the following parameters were important: the

  4. Trichloroethylene biotransformation and its role in mutagenicity, carcinogenicity and target organ toxicity.

    Science.gov (United States)

    Lash, Lawrence H; Chiu, Weihsueh A; Guyton, Kathryn Z; Rusyn, Ivan

    2014-01-01

    Metabolism is critical for the mutagenicity, carcinogenicity, and other adverse health effects of trichloroethylene (TCE). Despite the relatively small size and simple chemical structure of TCE, its metabolism is quite complex, yielding multiple intermediates and end-products. Experimental animal and human data indicate that TCE metabolism occurs through two major pathways: cytochrome P450 (CYP)-dependent oxidation and glutathione (GSH) conjugation catalyzed by GSH S-transferases (GSTs). Herein we review recent data characterizing TCE processing and flux through these pathways. We describe the catalytic enzymes, their regulation and tissue localization, as well as the evidence for transport and inter-organ processing of metabolites. We address the chemical reactivity of TCE metabolites, highlighting data on mutagenicity of these end-products. Identification in urine of key metabolites, particularly trichloroacetate (TCA), dichloroacetate (DCA), trichloroethanol and its glucuronide (TCOH and TCOG), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC), in exposed humans and other species (mostly rats and mice) demonstrates function of the two metabolic pathways in vivo. The CYP pathway primarily yields chemically stable end-products. However, the GST pathway conjugate S-(1,2-dichlorovinyl)glutathione (DCVG) is further processed to multiple highly reactive species that are known to be mutagenic, especially in kidney where in situ metabolism occurs. TCE metabolism is highly variable across sexes, species, tissues and individuals. Genetic polymorphisms in several of the key enzymes metabolizing TCE and its intermediates contribute to variability in metabolic profiles and rates. In all, the evidence characterizing the complex metabolism of TCE can inform predictions of adverse responses including mutagenesis, carcinogenesis, and acute and chronic organ-specific toxicity.

  5. Trichloroethylene Biotransformation and its Role in Mutagenicity, Carcinogenicity and Target Organ Toxicity

    Science.gov (United States)

    Lash, Lawrence H.; Chiu, Weihsueh A.; Guyton, Kathryn Z.; Rusyn, Ivan

    2014-01-01

    Metabolism is critical for the mutagenicity, carcinogenicity, and other adverse health effects of trichloroethylene (TCE). Despite the relatively small size and simple chemical structure of TCE, its metabolism is quite complex, yielding multiple intermediates and end-products. Experimental animal and human data indicate that TCE metabolism occurs through two major pathways: cytochrome P450 (CYP)-dependent oxidation and glutathione (GSH) conjugation catalyzed by GSH S-transferases (GSTs). Herein we review recent data characterizing TCE processing and flux through these pathways. We describe the catalytic enzymes, their regulation and tissue localization, as well as the evidence for transport and inter-organ processing of metabolites. We address the chemical reactivity of TCE metabolites, highlighting data on mutagenicity of these end-products. Identification in urine of key metabolites, particularly trichloroacetate (TCA), dichloroacetate (DCA), trichloroethanol and its glucuronide (TCOH and TCOG), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC), in exposed humans and other species (mostly rats and mice) demonstrates function of the two metabolic pathways in vivo. The CYP pathway primarily yields chemically stable end-products. However, the GST pathway conjugate S-(1,2-dichlorovinyl)glutathione (DCVG) is further processed to multiple highly reactive species that are known to be mutagenic, especially in kidney where in situ metabolism occurs. TCE metabolism is highly variable across sexes, species, tissues and individuals. Genetic polymorphisms in several of the key enzymes metabolizing TCE and its intermediates contribute to variability in metabolic profiles and rates. In all, the evidence characterizing the complex metabolism of TCE can inform predictions of adverse responses including mutagenesis, carcinogenesis, and acute and chronic organ-specific toxicity. PMID:25484616

  6. Quality of laboratory studies assessing effects of Bt-proteins on non-target organisms: minimal criteria for acceptability.

    Science.gov (United States)

    De Schrijver, Adinda; Devos, Yann; De Clercq, Patrick; Gathmann, Achim; Romeis, Jörg

    2016-08-01

    The potential risks that genetically modified plants may pose to non-target organisms and the ecosystem services they contribute to are assessed as part of pre-market risk assessments. This paper reviews the early tier studies testing the hypothesis whether exposure to plant-produced Cry34/35Ab1 proteins as a result of cultivation of maize 59122 is harmful to valued non-target organisms, in particular Arthropoda and Annelida. The available studies were assessed for their scientific quality by considering a set of criteria determining their relevance and reliability. As a case-study, this exercise revealed that when not all quality criteria are met, weighing the robustness of the study and its relevance for risk assessment is not obvious. Applying a worst-case expected environmental concentration of bioactive toxins equivalent to that present in the transgenic crop, confirming exposure of the test species to the test substance, and the use of a negative control were identified as minimum criteria to be met to guarantee sufficiently reliable data. This exercise stresses the importance of conducting studies meeting certain quality standards as this minimises the probability of erroneous or inconclusive results and increases confidence in the results and adds certainty to the conclusions drawn.

  7. Detection of genetically modified organisms (GMOs using isothermal amplification of target DNA sequences

    Directory of Open Access Journals (Sweden)

    La Mura Maurizio

    2009-02-01

    Full Text Available Abstract Background The most common method of GMO detection is based upon the amplification of GMO-specific DNA amplicons using the polymerase chain reaction (PCR. Here we have applied the loop-mediated isothermal amplification (LAMP method to amplify GMO-related DNA sequences, 'internal' commonly-used motifs for controlling transgene expression and event-specific (plant-transgene junctions. Results We have tested the specificity and sensitivity of the technique for use in GMO studies. Results show that detection of 0.01% GMO in equivalent background DNA was possible and dilutions of template suggest that detection from single copies of the template may be possible using LAMP. Conclusion This work shows that GMO detection can be carried out using LAMP for routine screening as well as for specific events detection. Moreover, the sensitivity and ability to amplify targets, even with a high background of DNA, here demonstrated, highlights the advantages of this isothermal amplification when applied for GMO detection.

  8. Metallothionein is induced and trace element balance changed in target organs of a common viral infection

    International Nuclear Information System (INIS)

    Ilbaeck, Nils-Gunnar; Glynn, Anders W.; Wikberg, Lotta; Netzel, Elvy; Lindh, Ulf

    2004-01-01

    In experimental studies on the common human coxsackievirus B type 3 (CB3) infection, administered cadmium (Cd) is known to accumulate in the liver and kidneys. CB3 adapted to Balb/c mice was used to study whether infection affects the Cd-binding protein, metallothionein (MT) and if this alters the normal physiological trace element balance in the liver, kidney, spleen and brain. On day 3 of infection, degradation of liver proteins (44%, P<0.01) occurred, whereas in the spleen, protein increased (63%, P<0.05). The infection increased MT five-fold (P<0.01) in liver and kidneys, and in spleen by 34% (P<0.05). A redistribution of Cd and copper (Cu) from the liver to the kidney was associated with this increase in MT, resulting in an increased (P<0.01) kidney/liver ratio for both elements. The infection increased the zinc (Zn) concentration more in the kidney than in the liver, but the kidney/liver ratio was not significantly affected. Results show that MT is increased in several organs during the early phase of infection and is associated with redistribution of both essential and non-essential trace elements. This may be a normal response in common infections that could adversely influence the pathogenesis when the host is concomitantly exposed to potentially toxic trace elements, even at levels in the physiological range

  9. 3D NIR-II Molecular Imaging Distinguishes Targeted Organs with High-Performance NIR-II Bioconjugates.

    Science.gov (United States)

    Zhu, Shoujun; Herraiz, Sonia; Yue, Jingying; Zhang, Mingxi; Wan, Hao; Yang, Qinglai; Ma, Zhuoran; Wang, Yan; He, Jiahuan; Antaris, Alexander L; Zhong, Yeteng; Diao, Shuo; Feng, Yi; Zhou, Ying; Yu, Kuai; Hong, Guosong; Liang, Yongye; Hsueh, Aaron J; Dai, Hongjie

    2018-02-15

    Greatly reduced scattering in the second near-infrared (NIR-II) region (1000-1700 nm) opens up many new exciting avenues of bioimaging research, yet NIR-II fluorescence imaging is mostly implemented by using nontargeted fluorophores or wide-field imaging setups, limiting the signal-to-background ratio and imaging penetration depth due to poor specific binding and out-of-focus signals. A newly developed high-performance NIR-II bioconjugate enables targeted imaging of a specific organ in the living body with high quality. Combined with a home-built NIR-II confocal set-up, the enhanced imaging technique allows 900 µm-deep 3D organ imaging without tissue clearing techniques. Bioconjugation of two hormones to nonoverlapping NIR-II fluorophores facilitates two-color imaging of different receptors, demonstrating unprecedented multicolor live molecular imaging across the NIR-II window. This deep tissue imaging of specific receptors in live animals allows development of noninvasive molecular imaging of multifarious models of normal and neoplastic organs in vivo, beyond the traditional visible to NIR-I range. The developed NIR-II fluorescence microscopy will become a powerful imaging technique for deep tissue imaging without any physical sectioning or clearing treatment of the tissue. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Spatial organization of the cytoskeleton enhances cargo delivery to specific target areas on the plasma membrane of spherical cells

    Science.gov (United States)

    Hafner, Anne E.; Rieger, Heiko

    2016-12-01

    Intracellular transport is vital for the proper functioning and survival of a cell. Cargo (proteins, vesicles, organelles, etc) is transferred from its place of creation to its target locations via molecular motor assisted transport along cytoskeletal filaments. The transport efficiency is strongly affected by the spatial organization of the cytoskeleton, which constitutes an inhomogeneous, complex network. In cells with a centrosome microtubules grow radially from the central microtubule organizing center towards the cell periphery whereas actin filaments form a dense meshwork, the actin cortex, underneath the cell membrane with a broad range of orientations. The emerging ballistic motion along filaments is frequently interrupted due to constricting intersection nodes or cycles of detachment and reattachment processes in the crowded cytoplasm. In order to investigate the efficiency of search strategies established by the cell’s specific spatial organization of the cytoskeleton we formulate a random velocity model with intermittent arrest states. With extensive computer simulations we analyze the dependence of the mean first passage times for narrow escape problems on the structural characteristics of the cytoskeleton, the motor properties and the fraction of time spent in each state. We find that an inhomogeneous architecture with a small width of the actin cortex constitutes an efficient intracellular search strategy.

  11. Spatial organization of the cytoskeleton enhances cargo delivery to specific target areas on the plasma membrane of spherical cells.

    Science.gov (United States)

    Hafner, Anne E; Rieger, Heiko

    2016-11-15

    Intracellular transport is vital for the proper functioning and survival of a cell. Cargo (proteins, vesicles, organelles, etc) is transferred from its place of creation to its target locations via molecular motor assisted transport along cytoskeletal filaments. The transport efficiency is strongly affected by the spatial organization of the cytoskeleton, which constitutes an inhomogeneous, complex network. In cells with a centrosome microtubules grow radially from the central microtubule organizing center towards the cell periphery whereas actin filaments form a dense meshwork, the actin cortex, underneath the cell membrane with a broad range of orientations. The emerging ballistic motion along filaments is frequently interrupted due to constricting intersection nodes or cycles of detachment and reattachment processes in the crowded cytoplasm. In order to investigate the efficiency of search strategies established by the cell's specific spatial organization of the cytoskeleton we formulate a random velocity model with intermittent arrest states. With extensive computer simulations we analyze the dependence of the mean first passage times for narrow escape problems on the structural characteristics of the cytoskeleton, the motor properties and the fraction of time spent in each state. We find that an inhomogeneous architecture with a small width of the actin cortex constitutes an efficient intracellular search strategy.

  12. Placental Nano-vesicles Target to Specific Organs and Modulate Vascular Tone In Vivo.

    Science.gov (United States)

    Tong, Mancy; Stanley, Joanna L; Chen, Q; James, Joanna L; Stone, Peter R; Chamley, Larry W

    2017-11-01

    How do nano-vesicles extruded from normal first trimester human placentae affect maternal vascular function? Placental nano-vesicles affect the ability of systemic mesenteric arteries to undergo endothelium- and nitric oxide- (NO-) dependent vasodilation in vivo in pregnant mice. Dramatic cardiovascular adaptations occur during human pregnancy, including a substantial decrease in total peripheral resistance in the first trimester. The human placenta constantly extrudes extracellular vesicles that can enter the maternal circulation and these vesicles may play an important role in feto-maternal communication. Human placental nano-vesicles were administered into CD1 mice via a tail vein and their localization and vascular effects at 30 min and 24 h post-injection were investigated. Nano-vesicles from normal first trimester human placentae were collected and administered into pregnant (D12.5) or non-pregnant female mice. After either 30 min or 24 h of exposure, all major organs were dissected for imaging (n = 7 at each time point) while uterine and mesenteric arteries were dissected for wire myography (n = 6 at each time point). Additional in vitro studies using HMEC-1 endothelial cells were also conducted to investigate the kinetics of interaction between placental nano-vesicles and endothelial cells. Nano-vesicles from first trimester human placentae localized to the lungs, liver and kidneys 24 h after injection into pregnant mice (n = 7). Exposure of pregnant mice to placental nano-vesicles for 30 min in vivo increased the vasodilatory response of mesenteric arteries to acetylcholine, while exposure for 24 h had the opposite effect (P nano-vesicles did not affect the function of uterine arteries or mesenteric arteries from non-pregnant mice. Placental nano-vesicles rapidly interacted with endothelial cells via a combination of phagocytosis, endocytosis and cell surface binding in vitro. N/A. As it is not ethical to administer labelled placental nano-vesicles to

  13. What are the effects of severe visual impairment on the cortical organization and connectivity of primary visual cortex?

    OpenAIRE

    DeLaine D Larsen; Julie D Luu; Marie E Burns; Marie E Burns; Leah Krubitzer; Leah Krubitzer

    2009-01-01

    The organization and connections of the primary visual area (V1) were examined in mice that lacked functional rods (Gnat-/-), but had normal cone function. Because mice are nocturnal and rely almost exclusively on rod vision for normal behaviors, the Gnat-/- mice used in the present study are considered functionally blind. Our goal was to determine if visual cortex is reorganized in these mice, and to examine the neuroanatomical connections that may subserve reorganization. We found that m...

  14. Control of sand flies with attractive toxic sugar baits (ATSB) and potential impact on non-target organisms in Morocco.

    Science.gov (United States)

    Qualls, Whitney A; Müller, Gunter C; Khallaayoune, Khalid; Revay, Edita E; Zhioua, Elyes; Kravchenko, Vasiliy D; Arheart, Kristopher L; Xue, Rui-De; Schlein, Yosef; Hausmann, Axel; Kline, Daniel L; Beier, John C

    2015-02-08

    The persistence and geographical expansion of leishmaniasis is a major public health problem that requires the development of effective integrated vector management strategies for sand fly control. Moreover, these strategies must be economically and environmentally sustainable approaches that can be modified based on the current knowledge of sand fly vector behavior. The efficacy of using attractive toxic sugar baits (ATSB) for sand fly control and the potential impacts of ATSB on non-target organisms in Morocco was investigated. Sand fly field experiments were conducted in an agricultural area along the flood plain of the Ourika River. Six study sites (600 m x 600 m); three with "sugar rich" (with cactus hedges bearing countless ripe fruits) environments and three with "sugar poor" (green vegetation only suitable for plant tissue feeding) environments were selected to evaluate ATSB, containing the toxin, dinotefuran. ATSB applications were made either with bait stations or sprayed on non-flowering vegetation. Control sites were established in both sugar rich and sugar poor environments. Field studies evaluating feeding on vegetation treated with attractive (non-toxic) sugar baits (ASB) by non-target arthropods were conducted at both sites with red stained ASB applied to non-flowering vegetation, flowering vegetation, or on bait stations. At both the sites, a single application of ATSB either applied to vegetation or bait stations significantly reduced densities of both female and male sand flies (Phlebotomus papatasi and P. sergenti) for the five-week trial period. Sand fly populations were reduced by 82.8% and 76.9% at sugar poor sites having ATSB applied to vegetation or presented as a bait station, respectively and by 78.7% and 83.2%, respectively at sugar rich sites. The potential impact of ATSB on non-targets, if applied on green non-flowering vegetation and bait stations, was low for all non-target groups as only 1% and 0.7% were stained with non-toxic bait

  15. [Correlation Study on Pathological Characteristics of Target Organs and Excess Evil Syndrome in IgA Nephropathy].

    Science.gov (United States)

    Wan, Ting-xin; Dai, En-lai; Wang, Wen-ge; Liu, Tian-xi; Liu, Feng; Li, Yin-xia; Jiang, Min; Zhao, Zhu-hua; Yang, Bai-quan

    2015-09-01

    To explore the correlation between pathological characteristics of target organs and excess evil syndrome in IgA nephropathy. Data were collected in multicenter cooperation. Totally 266 IgA nephropathy patients were typed into exogenous wind-heat affection syndrome (49 cases), lower energizer damp-heat syndrome (100 cases), damp-phlegm syndrome (43 cases), and blood stasis syndrome (74 cases). Meanwhile, percutaneous renal biopsy was performed in all patients for Hass classification, Oxford classification, Katafuchi integral, and Jiang's classification methods. The correlation between excess evil syndrome and pathological index was analyzed. Four syndrome types were correlated with their Hass levels (r = 0. 341, P syndrome was correlated with segmental proliferation of endothelial cells and damaged active lesions of segmental capillary loops. Lower-energizer damp-heat syndrome was associated with Hass III level, destroying active lesions of capillary loops, segmental proliferation of endothelial cells, glomerular segmental lesions, focal interstitial infiltration of inflammatory cells, focal interstitial fibrosis and tubular atrophy. Blood stasis syndrome was associated with Hass IV level, glomerular sclerosis, segmental glomerulosclerosis (S)/adhesion, mesangial hypercellularity (M), angiohyalinosis, multi-foci interstitial infiltration of inflammatory cells, multi-foci interstitial fibrosis and tubular atrophy. Phlegm-damp syndrome had higher proportions of Hass I and III levels, but with no association with other pathological parameters. Excess evil syndrome was associated with partial pathological characteristics of IgA nephropathy. It could reflect pathological damage degree of target organs, activities, chronic lesions, and prognosis of IgA nephropathy to certain extent. Correlated pathological characteristics and its evolution could indicate excess evil syndrome types and their evolution rules.

  16. Compatibility of organic farming treatments against Monosteira unicostata with non-target arthropod fauna of almond trees canopy

    Directory of Open Access Journals (Sweden)

    Ismael Sánchez-Ramos

    2017-07-01

    Full Text Available Field trials had shown that 1-2 applications of kaolin and potassium salts of fatty acids combined with thyme essential oil (PSTEO reduced the abundance of the lace bug Monosteira unicostata (Mulsant & Rey (Hemiptera: Tingidae, an important pest of almond trees in the Mediterranean region. These products could be useful for the control of this pest in organic production of almonds, but higher number of applications could be necessary. However, the possible detrimental effects on the almond orchard ecosystem should be evaluated. In the present work, the effects observed on the non-target arthropod fauna of the almond trees canopy in those field assays are shown. First, a comprehensive report of the non-target arthropod fauna of the almond tree is provided. Regarding natural enemies, most of the predatory arthropods captured were spiders belonging to different families like Salticidae, Thomisidae, Philodromidae, Theridiidae, Araneidae or Oxyopidae. Other predatory families that appeared in significant numbers were Chrysopidae, Anthocoridae, Aeolothripidae, Coccinellidae, Phytoseiidae, Erythraeidae or Forficulidae. Among parasitoids, the most abundant families were Eulophidae, Scelionidae and Dryinidae. Kaolin reduced the abundance of natural enemies and other non-target arthropods as well as their diversity and number of species. On the contrary, PSTEO only produced a slight reduction in the number of natural enemies, whereas no effect was found on the diversity and species richness. These effects were observed despite the reduced number of applications, so greater effect is expected if its frequency is increased in order to achieve an efficient control of M. unicostata.

  17. Effect of positively charged particles on sputtering damage of organic electro-luminescent diodes with Mg:Ag alloy electrodes fabricated by facing target sputtering

    Directory of Open Access Journals (Sweden)

    Kouji Suemori

    2017-04-01

    Full Text Available We investigated the influence of the positively charged particles generated during sputtering on the performances of organic light-emitting diodes (OLEDs with Mg:Ag alloy electrodes fabricated by sputtering. The number of positively charged particles increased by several orders of magnitude when the target current was increased from 0.1 A to 2.5 A. When a high target current was used, many positively charged particles with energies higher than the bond energy of single C–C bonds, which are typically found in organic molecules, were generated. In this situation, we observed serious OLED performance degradation. On the other hand, when a low target current was used, OLED performance degradation was not observed when the number of positively charged particles colliding with the organic underlayer increased. We concluded that sputtering damage caused by positively charged particles can be avoided by using a low target current.

  18. What are the Effects of Severe Visual Impairment on the Cortical Organization and Connectivity of Primary Visual Cortex?

    Science.gov (United States)

    Larsen, Delaine D; Luu, Julie D; Burns, Marie E; Krubitzer, Leah

    2009-01-01

    The organization and connections of the primary visual area (V1) were examined in mice that lacked functional rods (Gnat-/-), but had normal cone function. Because mice are nocturnal and rely almost exclusively on rod vision for normal behaviors, the Gnat-/- mice used in the present study are considered functionally blind. Our goal was to determine if visual cortex is reorganized in these mice, and to examine the neuroanatomical connections that may subserve reorganization. We found that most neurons in V1 responded to auditory, or some combination of auditory, somatosensory, and/or visual stimulation. We also determined that cortical connections of V1 in Gnat-/- mice were similar to those in normal animals, but even in normal animals, there is sparse input from auditory cortex (AC) to V1. An important observation was that most of the subcortical inputs to V1 were from thalamic nuclei that normally project to V1 such as the lateral geniculate (LG), lateral posterior (LP), and lateral dorsal (LD) nuclei. However, V1 also received some abnormal subcortical inputs from the anterior thalamic nuclei, the ventral posterior, the ventral lateral and the posterior nuclei. While the vision generated from the small number of cones appears to be sufficient to maintain most of the patterns of normal connectivity, the sparse abnormal thalamic inputs to VI, existing inputs from AC, and possibly abnormal inputs to LG and LP may be responsible for generating the alterations in the functional organization of V1.

  19. What are the effects of severe visual impairment on the cortical organization and connectivity of primary visual cortex?

    Directory of Open Access Journals (Sweden)

    DeLaine D Larsen

    2009-12-01

    Full Text Available The organization and connections of the primary visual area (V1 were examined in mice that lacked functional rods (Gnat-/-, but had normal cone function. Because mice are nocturnal and rely almost exclusively on rod vision for normal behaviors, the Gnat-/- mice used in the present study are considered functionally blind. Our goal was to determine if visual cortex is reorganized in these mice, and to examine the neuroanatomical connections that may subserve reorganization. We found that most neurons in V1 responded to auditory, or some combination of auditory, somatosensory, and/or visual stimulation. We also determined that cortical connections of V1 in Gnat-/- mice were similar to those in normal animals, but even in normal animals, there is sparse input from auditory cortex to V1. An important observation was that most of the subcortical inputs to V1 were from thalamic nuclei that normally project to V1 such as the lateral geniculate (LG, lateral posterior (LP, and lateral dorsal (LD nuclei. However, V1 also received some abnormal subcortical inputs from the anterior thalamic nuclei, the ventral posterior, the ventral lateral and the posterior nuclei. While the vision generated from the small number of cones appears to be sufficient to maintain most of the patterns of normal connectivity, the sparse abnormal thalamic inputs to VI, existing inputs from auditory cortex, and possibly abnormal inputs to LG and LP may be responsible for generating the alterations in the functional organization of V1.

  20. Self-organizing molecular fingerprints: a ligand-based view on drug-like chemical space and off-target prediction.

    Science.gov (United States)

    Schneider, Gisbert; Tanrikulu, Yusuf; Schneider, Petra

    2009-04-01

    Reliable prediction of multiple ligand-receptor interactions for a given bioactive compound helps recognize and understand off-target effects, and enables drug re-purposing and scaffold-hopping in lead discovery. We developed a ligand-based computational method for drug-target prediction that is independent from protein structural analysis. The idea is to infer drug targets from the pharmacophoric feature similarity of known ligands, and define functional target similarity from a ligand perspective, which also provides access to targets with unknown structures. First, known ligands were represented by topological pharmacophoric features. Then, the self-organizing map technique was used to generate fingerprint patterns for similarity analysis, where each resulting fingerprint represents a drug target. Target fingerprints were clustered and analyzed for correlations. Well-structured dendrograms were obtained presenting interpretable and meaningful relationships between drug targets. Self-organization of fingerprints reduces noise from molecular pharmacophore descriptors, captures their essential features, and reveals potential cross-activities of ligand classes and off-target effects of bioactive compounds.

  1. Facile biosynthesis of silver nanoparticles using Barleria cristata: mosquitocidal potential and biotoxicity on three non-target aquatic organisms.

    Science.gov (United States)

    Govindarajan, Marimuthu; Benelli, Giovanni

    2016-03-01

    Mosquitoes (Diptera: Culicidae) act as vectors of important pathogens and parasites, such as malaria, dengue, chikungunya, Japanese encephalitis and lymphatic filariasis. The use of synthetic mosquitocides often leads to high operational costs and adverse non-target effects. Recently, plant-borne compounds have been proposed for rapid extracellular biosynthesis of mosquitocidal nanoparticles. However, the impact of these nanomosquitocides against biological control agents of mosquito larval populations has been poorly studied. In this research, we biosynthesized silver nanoparticles (Ag NP) using the Barleria cristata leaf extract as a reducing and stabilizing agent. The biosynthesis of Ag NP was confirmed analyzing the excitation of surface plasmon resonance using ultraviolet-visible (UV-vis) spectrophotometry. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed the clustered and irregular shapes of Ag NP. The presence of silver was confirmed by energy-dispersive X-ray (EDX) spectroscopy. Fourier transform infrared (FTIR) spectroscopy investigated the identity of secondary metabolites, which may also act as Ag NP capping agents. The acute toxicity of B. cristata leaf extract and biosynthesized Ag NP was evaluated against larvae of Anopheles subpictus, Aedes albopictus, and Culex tritaeniorhynchus. Compared to the leaf aqueous extract, biosynthesized Ag NP showed higher toxicity against An. subpictus, Ae. albopictus, and Cx. tritaeniorhynchus with lethal concentration (LC)50 values of 12.46, 13.49, and 15.01 μg/mL, respectively. Notably, biosynthesized Ag NP were found safer to non-target organisms Diplonychus indicus, Anisops bouvieri, and Gambusia affinis, with respective LC50 values ranging from 633.26 to 866.92 μg/mL. Overall, our results highlight that B. cristata-fabricated Ag NP are a promising and eco-friendly tool against young instar populations of mosquito vectors of medical and veterinary importance.

  2. Roles of calcium and IP3 in impaired colon contractility of rats following multiple organ dysfunction syndrome

    Directory of Open Access Journals (Sweden)

    C. Zheyu

    2007-10-01

    Full Text Available The purpose of the present study was to explore changes in rat colon motility, and determine the roles of calcium and inositol (1,4,5-triphosphate (IP3 in colon dysmotility induced by multiple organ dysfunction syndrome (MODS caused by bacteria peritonitis. The number of stools, the contractility of the muscle strips and the length of smooth muscle cells (SMC in the colon, the concentration of calcium and IP3 in SMC, and serum nitric oxide were measured. Number of stools, fecal weight, IP3 concentration in SMC and serum nitric oxide concentration were 0.77 ± 0.52 pellets, 2.51 ± 0.39 g, 4.14 ± 2.07 pmol/tube, and 113.95 ± 37.89 µmol/L, respectively, for the MODS group (N = 11 vs 1.54 ± 0.64 pellets, 4.32 ± 0.57 g, 8.19 ± 3.11 pmol/tube, and 37.42 ± 19.56 µmol/L for the control group (N = 20; P < 0.05. After treatment with 0.1 mM acetylcholine and 0.1 M potassium chloride, the maximum contraction stress of smooth muscle strips, the length of SMC and the changes of calcium concentration were 593 ± 81 and 458 ± 69 g/cm³, 48.1 ± 11.8 and 69.2 ± 15.7 µM, 250 ± 70 and 167 ± 48%, respectively, for the control group vs 321 ± 53 and 284 ± 56 g/cm³, 65.1 ± 18.5 and 87.2 ± 23.7 µM, 127 ± 35 and 112 ± 35% for the MODS group (P < 0.05. Thus, colon contractility was decreased in MODS, a result possibly related to reduced calcium concentration and IP3 in SMC.

  3. Selective Nanoparticle Targeting of the Renal Tubules.

    Science.gov (United States)

    Williams, Ryan M; Shah, Janki; Tian, Helen S; Chen, Xi; Geissmann, Frederic; Jaimes, Edgar A; Heller, Daniel A

    2018-01-01

    Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases. © 2017 American Heart Association, Inc.

  4. Targeted and non-targeted boron complex formation followed by electrospray Fourier transform ion cyclotron mass spectrometry: a novel approach for identifying boron esters with natural organic matter.

    Science.gov (United States)

    Gaspar, Andras; Lucio, Marianna; Harir, Mourad; Schmitt-Kopplin, Philippe

    2011-01-01

    The formation of boron esters was investigated in peat-soluble humified materials with a detailed molecular-level description of boron-organic interactions. Thousands of individually baseline separated signals were obtained from the analysis of natural organic matter of peat samples, using Fourier transform ion cyclotron resonance mass spectrometry. This technique offers unsurpassed isotope-specific mass resolution that can lead to precise molecular formula assignments by means of mathematical data analysis and visualisation techniques, such as mass defect (Kendrick) or elemental ratio (van Krevelen) plots. The analysis of potential boron binding structures within the sample of natural organic matter was described based on prior results. Herein, we describe an algorithm that can be used to effectively distinguish and filter complexes through data obtained from boron-enriched systems with highly intricate mass spectra, such as natural organic matter.

  5. The beta-receptor blocker metoprolol alters detoxification processes in the non-target organism Dreissena polymorpha

    Energy Technology Data Exchange (ETDEWEB)

    Contardo-Jara, Valeska, E-mail: contardo@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Pflugmacher, Stephan, E-mail: pflugmacher@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Nuetzmann, Gunnar, E-mail: nuetzmann@igb-berlin.d [Dpt. Ecohydrology, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Kloas, Werner, E-mail: werner.kloas@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Wiegand, Claudia, E-mail: wiegand@biology.sdu.d [University of Southern Denmark Institute of Biology, Campusvej 55, 5230 Odense M (Denmark)

    2010-06-15

    Due to increasing amounts of pharmaceutically active compounds (PhACs) in the aquatic environment, their largely unknown effects to non-target organisms need to be assessed. This study examined physiological changes in the freshwater mussel Dreissena polymorpha exposed to increasing concentrations (0.534, 5.34, 53.4 and 534 mug L{sup -1}) of the beta-blocker metoprolol in a flow-through system for seven days. The two lower concentrations represent the environmentally relevant range. Surprisingly, metallothionein mRNA was immediately up-regulated in all treatments. For the two higher concentrations mRNA up-regulation in gills was found for P-glycoprotein after one day, and after four days for pi class glutathione S-transferase, demonstrating elimination and biotransformation processes, respectively. Additionally, catalase and superoxide dismutase were up-regulated in the digestive gland indicating oxidative stress. In all treated mussels a significant up-regulation of heat shock protein mRNA was observed in gills after four days, which suggests protein damage and the requirement for repair processes. Metoprolol was 20-fold bioaccumulated for environmentally relevant concentrations. - Evidence for significant physiological changes in an aquatic mollusc due to exposure to a pharmaceutically active compound detected by real-time PCR.

  6. Targeted Construction of Light-Harvesting Metal-Organic Frameworks Featuring Efficient Host-Guest Energy Transfer.

    Science.gov (United States)

    Zhao, Xiaoyu; Song, Xiaoyu; Li, Yang; Chang, Ze; Chen, Long

    2018-02-14

    Metal-organic frameworks (MOFs) have emerged as promising light-harvesting platforms for energy-transfer materials. However, the targeted construction of MOFs with desirable photophysical properties and pore structures is still a challenge. Herein, 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethene (tppe) is selected as the ligand for the construction of light-harvesting MOFs due to its highly emissive and rigid backbone, which could benefit the light-harvesting performance of the MOFs. Three MOFs (MOFs 1-3) were obtained on the basis of different metal centers (Zn 2+ and Cd 2+ ) and carboxylate building blocks. The complete structure characterization of the MOFs helps the illustration of the principles for structure tuning of this system. All three MOFs exhibit strong tppe-originated photoluminescence emission, with quantum yields as high as 47.6%. The fluorescence quantum yield and time-resolved fluorescence studies reveal that a remarkable energy-transfer efficiency (up to 96%) was achieved in this system. These results clearly indicate tppe-MOFs could be promising light-harvesting materials.

  7. Assessing environmental impacts of genetically modified plants on non-target organisms: The relevance of in planta studies.

    Science.gov (United States)

    Arpaia, Salvatore; Birch, A Nicholas E; Kiss, Jozsef; van Loon, Joop J A; Messéan, Antoine; Nuti, Marco; Perry, Joe N; Sweet, Jeremy B; Tebbe, Christoph C

    2017-04-01

    In legal frameworks worldwide, genetically modified plants (GMPs) are subjected to pre-market environmental risk assessment (ERA) with the aim of identifying potential effects on the environment. In the European Union, the EFSA Guidance Document introduces the rationale that GMPs, as well as their newly produced metabolites, represent the potential stressor to be evaluated during ERA. As a consequence, during several phases of ERA for cultivation purposes, it is considered necessary to use whole plants or plant parts in experimental protocols. The importance of in planta studies as a strategy to address impacts of GMPs on non-target organisms is demonstrated, to evaluate both effects due to the intended modification in plant phenotype (e.g. expression of Cry proteins) and effects due to unintended modifications in plant phenotype resulting from the transformation process (e.g. due to somaclonal variations or pleiotropic effects). In planta tests are also necessary for GMPs in which newly expressed metabolites cannot easily be studied in vitro. This paper reviews the scientific literature supporting the choice of in planta studies as a fundamental tool in ERA of GMPs in cultivation dossiers; the evidence indicates they can realistically mimic the ecological relationships occurring in their receiving environments and provide important insights into the biology and sustainable management of GMPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The effects of organochlorine pesticides on some non-target organisms in maize and cowpea agro-ecosystems in Ghana

    International Nuclear Information System (INIS)

    Montford, K.G.

    1997-01-01

    In order to study the effects of organochlorine pesticides on non-target organisms under tropical conditions, a three-year study was conducted in Ghana applying lindane at 1 kg AI. ha -1 and endosulfan at 0.75 kg AI. ha -1 to maize and cowpeas respectively. The endosulfan treatment was preceded by two consecutive treatments with cypermethrin at 50 g AI ha -1 . Lindane significantly reduced the numbers of ants, spiders and springtails trapped though the numbers of ants and spiders generally recovered within the cropping period. Lindane significantly increased the numbers of leafhoppers caught from maize plots probably due to the elimination of a natural enemy. Ant, spider and springtail numbers were also significantly reduced by the endosulfan treatment in cowpea plots 5. Lindane did not significantly increase maize yields in two of the three years. Endosulfan contributed to significant yield increases and reduced seed damage in cowpeas. Neither lindane nor endosulfan seemed to have any significant adverse effects on the activities of soil microfauna and microflora based on the rates of decomposition of leaf discs buried in the experimental plots. (author). 12 refs, 10 figs, 9 tabs

  9. Influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis complicated by MODS

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2017-05-01

    Full Text Available Objective: To study the influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis accompanied by MODS. Methods: A total of 78 patients with severe acute pancreatitis complicated by MODS who were treated in our hospital between June 2012 and March 2016 were selected and divided into control group (n=39 and observation group (n=39 according to random number table. Control group were treated with routine treatment, observation group were treated with conventional treatment plus continuous blood purification, and serum inflammatory factors, liver function indexes and renal function indexes were compared between two groups of patients before and after treatment. Results: Before treatment, differences in serum levels of inflammatory factors, liver function indexes and renal function indexes were not statistically significant between two groups of patients. After treatment, serum inflammatory factors IL-6, IL-8, MCP-1 and HMGB1 levels of observation group were lower than those of control group, liver function indexes ALT, AST, TBIL and ALP levels of observation group were lower than those of control group, and renal function indexes Scr and BUN levels of observation group were lower than those of control group. Conclusion: Continuous blood purification can reduce the systemic inflammatory response as well as liver and kidney injury in patients with severe acute pancreatitis complicated by MODS.

  10. Toxicity evaluation of three pesticides on non-target aquatic and soil organisms: commercial formulation versus active ingredient.

    Science.gov (United States)

    Pereira, Joana L; Antunes, Sara C; Castro, Bruno B; Marques, Catarina R; Gonçalves, Ana M M; Gonçalves, Fernando; Pereira, Ruth

    2009-05-01

    The Ecological Risk Assessment of pesticides requires data regarding their toxicity to aquatic and terrestrial non-target species. Such requirements concern active ingredient(s), generally not considering the noxious potential of commercial formulations. This work intends to contribute with novel information on the effects of short-term exposures to two herbicides, with different modes of action (Spasor, Stam Novel Flo 480), and an insecticide (Lannate), as well as to corresponding active ingredients (Glyphosate, Propanil and Methomyl, respectively). The microalga Pseudokirchneriella subcapitata (growth inhibition), the cladoceran Daphnia magna (immobilisation), and the earthworm Eisenia andrei (avoidance behaviour) were used as test species. Both herbicides were innocuous to all test organisms at environmentally realistic concentrations, except for Stam and Propanil (highly toxic for Pseudokirchneriella; moderately toxic to Daphnia). Lannate and Methomyl were highly toxic to Daphnia and caused Eisenia to significantly avoid the spiked soil at realistic application rates. The toxicity of formulations either overestimated (e.g. Stam/Propanil for P. subcapitata) or underestimated (e.g. Stam/Propanil for D. magna) that of the active ingredient.

  11. Solitary Bone Plasmacytoma Progressing into Retroperitoneal Plasma Cell Myeloma with No Related End Organ or Tissue Impairment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gargi Tikku

    2014-09-01

    Full Text Available Solitary bone plasmacytomas and plasma cell myeloma are clonal proliferations of plasma cells. Many patients with solitary bone plasmacytomas develop plasma cell myeloma on follow-up. We present a case of a 70-year-old man who presented with fracture and a lytic lesion in the subtrochanteric region of the left femur and was assigned a diagnosis of solitary bone plasmacytoma. He received local curative radiotherapy. However, 4 months later his serum M protein and β2-microglobulin levels increased to 2.31 g/dL and 5.965 mg/L, respectively. He complained of abdominal fullness and constipation. Ultrasound and non-contrast CT imaging revealed multiple retroperitoneal masses. Colonoscopic examination was normal. Biopsy of the a retroperitoneal mass confirmed it to be a plasmacytoma. Repeat hemogram, blood urea, serum creatinine, skeletal survey, and bone marrow examination revealed no abnormalities. This is an unusual presentation of plasma cell myeloma, which manifested as multiple huge extramedullary retroperitoneal masses and arose from a solitary bone plasmacytoma, without related end organ or tissue impairment and bone marrow plasmacytosis. The patient succumbed to his disease 8 months after the appearance of the retroperitoneal masses. This case highlights the importance of close monitoring of patients diagnosed with solitary bone plasmacytoma with increased serum M protein and serum β2-microglobulin levels, so that early therapy can be instituted to prevent conversion to plasma cell myeloma.

  12. Structural and functional effects of herbicides on non-target organisms in aquatic ecosystems with an emphasis on atrazine

    Science.gov (United States)

    Fairchild, James; Kortekamp, Andreas

    2011-01-01

    for controlling nuisance aquatic vegetation. Although aquatic herbicide exposure has been widely documented, these exposures are not necessarily related to adverse non-target ecological effects on natural communities in aquatic environments. This chapter evaluates the potential for effects of herbicides on the structure and function of aquatic envrionments at the population, community, and ecosystem levels of biological organization. In this manuscript I examine several critical aspects of the subject matter area: primary herbicides in use and chemical modes of action; the regulatory process used for registration and risk assessment of herbicides; data regarding non-target risks and the relative sensitivity of aquatic plants, inveretebrates, and fish to herbicides; and emerging areas of science regarding the potential for endocrine-disrupting effects of herbicides on aquatic vertebrates. Much of the focus of this paper is on atrazine due to the extensive database which exists regarding its fate and effects. 

  13. Impaired CD163 Mediated Hemoglobin-Scavenging and Hemolytic Crisis in Patients Treated with CD33 Targeted Chemotherapy (Gemtuzumab Ozogamicin, MylotargTM)

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Hasle, Henrik; Friis-Hansen, Lennart

    2007-01-01

    Hemoglobin liberated to plasma during intravascular hemolyses is rapidly bound to haptoglobin. The hemoglobin-haptoglobin complexes undergo endocytosis through the monocyte/macrophage specific scavenger receptor for hemoglobin (CD163). This mechanism protects against oxidative and NO-scavenging...... adverse effects of free hemoglobin. In this study, we describe a novel syndrome of severe intravascular hemolysis and serious hemolytic crisis due to impaired hemoglobin scavenging in three acute myeloid leukemia patients following CD33-directed therapy with the immunotoxin gemtuzumab ozogamicin (GO......-expressing monocytes. We show that CD163 positive monocytes and bone marrow macrophages coexpress CD33 thus suggesting that the GO-induced cellular cytotoxicity of CD33 positive cells eradicates a significant part of the CD163 positive monocytes and macrophages. The patients had severe inflammation...

  14. Genome-wide gene expression profiling in Arabidopsis thaliana reveals new targets of abscisic acid and largely impaired gene regulation in the abi1-1 mutant.

    Science.gov (United States)

    Hoth, Stefan; Morgante, Michele; Sanchez, Juan-Pablo; Hanafey, Michael K; Tingey, Scott V; Chua, Nam-Hai

    2002-12-15

    The phytohormone abscisic acid (ABA) plays important regulatory roles in many plant developmental processes including seed dormancy, germination, growth, and stomatal movements. These physiological responses to ABA are in large part brought about by changes in gene expression. To study genome-wide ABA-responsive gene expression we applied massively parallel signature sequencing (MPSS) to samples from Arabidopsis thaliana wildtype (WT) and abi1-1 mutant seedlings. We identified 1354 genes that are either up- or downregulated following ABA treatment of WT seedlings. Among these ABA-responsive genes, many encode signal transduction components. In addition, we identified novel ABA-responsive gene families including those encoding ribosomal proteins and proteins involved in regulated proteolysis. In the ABA-insensitive mutant abi1-1, ABA regulation of about 84.5% and 6.9% of the identified genes was impaired or strongly diminished, respectively; however, 8.6% of the genes remained appropriately regulated. Compared to other methods of gene expression analysis, the high sensitivity and specificity of MPSS allowed us to identify a large number of ABA-responsive genes in WT Arabidopsis thaliana. The database given in our supplementary material (http://jcs.biologists.org/supplemental) provides researchers with the opportunity to rapidly assess whether genes of interest may be regulated by ABA. Regulation of the majority of the genes by ABA was impaired in the ABA-insensitive mutant abi1-1. However, a subset of genes continued to be appropriately regulated by ABA, which suggests the presence of at least two ABA signaling pathways, only one of which is blocked in abi1-1.

  15. An Aromatic Diamidine That Targets Kinetoplast DNA, Impairs the Cell Cycle in Trypanosoma cruzi, and Diminishes Trypomastigote Release from Infected Mammalian Host Cells.

    Science.gov (United States)

    Girard, Richard M B M; Crispim, Marcell; Stolić, Ivana; Damasceno, Flávia Silva; Santos da Silva, Marcelo; Pral, Eizabeth Mieko Furusho; Elias, Maria Carolina; Bajić, Miroslav; Silber, Ariel Mariano

    2016-10-01

    Trypanosoma cruzi is the etiological agent of Chagas disease, affecting approximately 10 million people in the Americas and with some 40 million people at risk. The objective of this study was to evaluate the anti-T. cruzi activity of three new diamidines that have a 3,4-ethylenedioxy extension of the thiophene core, designated MB17, MB19, and MB38. All three diamidines exhibited dose-dependent inhibition of epimastigote replication. The mechanisms of action of these diamidines were investigated. Unlike MB17 and MB19, MB38 exhibited a significant increase in the number of annexin-propidium iodide double-labeled cells compared to levels in control parasites. As MB17 had shown a lower 50% inhibitory concentration (IC50) against epimastigote growth, the mechanism of action of this drug was studied in more detail. MB17 triggered a decrease in the intracellular ATP levels. As a consequence, MB17 affected the genomic DNA and kinetoplast DNA (kDNA) and impaired the parasite cell cycle. Moreover, MB17 caused DNA fragmentation, with a more severe effect on kDNA than on nuclear DNA, resulting in dyskinetoplastic cells. MB17 was tested for toxicity and effectiveness for the treatment of infected CHO-K1 cells, exhibiting a 50% cytotoxic concentration (CC50) of 13.47 ± 0.37 μM and an IC50 of 0.14 ± 0.12 μM against trypomastigote release. MB17 also diminished the infection index by 60% at 0.5 μM. In conclusion, despite belonging to the same family, these diamidines have different efficiencies. To summarize, MB17 was the most potent of these diamidines against epimastigotes, producing DNA damage preferentially in kDNA, impairing the parasite cell cycle, and decreasing the infection index and trypomastigote release from infected mammalian host cells, with a high selectivity index (SI) (cruzi. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. A statistical simulation model for field testing of non-target organisms in environmental risk assessment of genetically modified plants.

    Science.gov (United States)

    Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore

    2014-04-01

    Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided.

  17. Targeting helicase-dependent amplification products with an electrochemical genosensor for reliable and sensitive screening of genetically modified organisms.

    Science.gov (United States)

    Moura-Melo, Suely; Miranda-Castro, Rebeca; de-Los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J; Dos Santos Junior, J Ribeiro; da Silva Fonseca, Rosana A; Lobo-Castañón, Maria Jesús

    2015-08-18

    Cultivation of genetically modified organisms (GMOs) and their use in food and feed is constantly expanding; thus, the question of informing consumers about their presence in food has proven of significant interest. The development of sensitive, rapid, robust, and reliable methods for the detection of GMOs is crucial for proper food labeling. In response, we have experimentally characterized the helicase-dependent isothermal amplification (HDA) and sequence-specific detection of a transgene from the Cauliflower Mosaic Virus 35S Promoter (CaMV35S), inserted into most transgenic plants. HDA is one of the simplest approaches for DNA amplification, emulating the bacterial replication machinery, and resembling PCR but under isothermal conditions. However, it usually suffers from a lack of selectivity, which is due to the accumulation of spurious amplification products. To improve the selectivity of HDA, which makes the detection of amplification products more reliable, we have developed an electrochemical platform targeting the central sequence of HDA copies of the transgene. A binary monolayer architecture is built onto a thin gold film where, upon the formation of perfect nucleic acid duplexes with the amplification products, these are enzyme-labeled and electrochemically transduced. The resulting combined system increases genosensor detectability up to 10(6)-fold, allowing Yes/No detection of GMOs with a limit of detection of ∼30 copies of the CaMV35S genomic DNA. A set of general utility rules in the design of genosensors for detection of HDA amplicons, which may assist in the development of point-of-care tests, is also included. The method provides a versatile tool for detecting nucleic acids with extremely low abundance not only for food safety control but also in the diagnostics and environmental control areas.

  18. A statistical simulation model for field testing of non-target organisms in environmental risk assessment of genetically modified plants

    Science.gov (United States)

    Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore

    2014-01-01

    Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided. PMID:24834325

  19. White coat effect and masked uncontrolled hypertension in treated hypertensive-diabetic patients: Prevalence and target organ damage.

    Science.gov (United States)

    Leiria, Liana F; Severo, Mateus D; Ledur, Priscila S; Becker, Alexandre D; Aguiar, Fernanda M; Massierer, Daniela; Freitas, Valéria C; Schaan, Beatriz D; Gus, Miguel

    2015-09-01

    The association between hypertensive phenotypes of controlled hypertension (CH), white-coat effect (WCE), masked uncontrolled hypertension (MUH) and sustained hypertension (SH) with target organ damage have not been clearly established in diabetic hypertensive treated patients. The present study aims to evaluate the prevalence of the four phenotypes considering the current cut-off points for office and 24 h-ambulatory blood pressure monitoring (ABPM) and the association with left ventricle hypertrophy (LVH), diastolic function and nephropathy. Cross-sectional study with 304 patients on anti-hypertensive treatment aged 57.6 ± 6.1 years, who were submitted to ABPM and echocardiography. They were classified into CH (normal office BP and ABPM), WCE (high office BP and normal ABPM), MUH (normal office BP and high ABPM), and SH (high office BP and ABPM). Median HbA1c and diabetes duration were 7.9% (6.8-9.2), and 10 years (5-16), respectively. Prevalences of CH, WCE, MUH and SH were 27.3%, 17.1%, 18.8%, and 36.8%. MUH prevalence was higher than previously described. There was a significant increasing trend across the four groups in variables related to LVH (P ABPM beyond the traditional cardiovascular risk stratification tools has limitations, but is still useful in high-risk patients. Longitudinal studies could better evaluate the role of the use of ABPM in this scenario. Cut-off points for normality of office and ABPM influence the prevalences of WCH and MUH. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  20. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Charles W. Wilkinson

    2012-02-01

    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  1. Vaccine Targeting of Subdominant CD8+ T Cell Epitopes Increases the Breadth of the T Cell Response upon Viral Challenge, but May Impair Immediate Virus Control

    DEFF Research Database (Denmark)

    Steffensen, Maria A; Pedersen, Louise Holm; Jahn, Marie Louise

    2016-01-01

    to a vaccine expressing the same Ag without its immunodominant epitope. We found that removal of the dominant epitope allowed the induction of CD8(+) T cell responses targeting at least two otherwise subdominant epitopes. Importantly, the overall magnitude of the induced T cell responses was similar, allowing......As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and......, hence, a greater efficiency in controlling escape variants. However, to our knowledge the evidence supporting this concept is limited at best. To improve upon this, we used the murine lymphocytic choriomeningitis virus model and adenoviral vectors to compare a vaccine expressing unmodified Ag...

  2. EU Water Framework Directive and Stockholm Convention: can we reach the targets for priority substances and persistent organic pollutants?

    Science.gov (United States)

    Fuerhacker, Maria

    2009-08-01

    Water is a renewable resource and acceptable quality is important for human health, ecological and economic reasons, but human activity can cause great damage to the natural aquatic environment. Managing the water cycle in a sustainable way is the key to protect natural resources and human health. On a global level, the microbiological contamination of water sources is a major problem in connection with poverty and the United Nations Millennium Development Declaration is an important initiative to handle this problem. In terms of environmental health, persistent organic pollutants (POPs) circulate globally; as they travel long distances, they are found in remote areas far from their original source of application and can cause damage wherever they move to. On a global scale, United Nations Environmental Programme (UNEP) issued the Stockholm Convention to reduce POPs; in the European Union (EU), one intention of the Water Framework Directive (WFD) is to reach the good chemical status of waters; beside these regulations, there are other directives in support of these goals. The aim of this paper is to discuss whether the Stockholm Convention and the WFD allows meeting the targets of protection of human and environmental health, which are established in the different directives and how could we approach the targets. The aims and scopes of different directives are compiled and compared with the actual quality of water, different approaches of standard settings are compared and potential treatment options are discussed. Under the Stockholm Convention on POPs, which came into force in May 2004, governments are required to develop a National Implementation Plan (NIP) setting out how they will address their obligations under the convention and how they will take measures to eliminate or reduce the release of POPs into the environment by the use of best available techniques (BAT) and application of best environmental practices (BEP). On a European level, the WFD has been in

  3. Organics.

    Science.gov (United States)

    Chian, Edward S. K.; DeWalle, Foppe B.

    1978-01-01

    Presents water analysis literature for 1978. This review is concerned with organics, and it covers: (1) detergents and surfactants; (2) aliphatic and aromatic hydrocarbons; (3) pesticides and chlorinated hydrocarbons; and (4) naturally occurring organics. A list of 208 references is also presented. (HM)

  4. Organizers.

    Science.gov (United States)

    Callison, Daniel

    2000-01-01

    Focuses on "organizers," tools or techniques that provide identification and classification along with possible relationships or connections among ideas, concepts, and issues. Discusses David Ausubel's research and ideas concerning advance organizers; the implications of Ausubel's theory to curriculum and teaching; "webbing," a…

  5. Organic solvents impair life-traits and biomarkers in the New Zealand mudsnail Potamopyrgus antipodarum (Gray) at concentrations below OECD recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Lecomte, V.; Noury, P.; Tutundjian, R. [Irstea, UR MAEP, Laboratoire d’écotoxicologie, 5 rue de la Doua, CS70077, 69626 Villeurbanne Cedex (France); Buronfosse, T. [VetAgro-Sup, Campus vétérinaire, Endocrinology Laboratory, 69280 Marcy l’Etoile (France); Garric, J. [Irstea, UR MAEP, Laboratoire d’écotoxicologie, 5 rue de la Doua, CS70077, 69626 Villeurbanne Cedex (France); Gust, M., E-mail: marion.gust@irstea.fr [Irstea, UR MAEP, Laboratoire d’écotoxicologie, 5 rue de la Doua, CS70077, 69626 Villeurbanne Cedex (France)

    2013-09-15

    Highlights: •Acetone (20 μl l{sup −1}) accelerates embryonic development in Potamopyrgus antipodarum. •Ethanol (20 μl l{sup −1}) decreases growth in juvenile mudsnails. •Acetone, ethanol, methanol and DMSO increase E2 levels in snails. •Carrier solvents impair gene expression. •DMSO is to be preferred. -- Abstract: Potamopyrgus antipodarum is a gastropod mollusk proposed for use in the development of reproduction tests within the Organization for Economic Cooperation and Development (OECD). Numerous chemicals, including endocrine disrupters, are relatively water-insoluble, and water-miscible solvents are currently used for testing them. OECD recommends a maximum concentration of 100 μl l{sup −1}. As several studies highlighted effects of lower concentrations of solvents, this study assessed the effects of 20 μl l{sup −1} acetone, ethanol, methanol and dimethylsulfoxide (DMSO) on juvenile and adult snails during 42 days. Ethanol decreased juvenile growth, while acetone increased the rate of embryonic development. All solvents increased estradiol-like levels in adult snails. DMSO only increased mRNA expression of vitellogenin-like gene, while acetone, ethanol and methanol decreased mRNA expression of three nuclear receptor (estrogen receptor-like, ecdysone-induced protein and chicken ovalbumin upstream promoter transcription factor) genes as well as of genes encoding proteins involved in genomic (prohibitin-2) and non-genomic (striatin) pathways of estrogens activity in vertebrates. This study highlights the confounding effects of low concentrations of solvents and recommends avoiding their use. Where solvent use is inevitable, their concentrations and type should be investigated for suitability for the measured endpoints prior to use in chemical testing strategies.

  6. Targeted management of organic resources for sustainably increasing soil organic carbon: Observations and perspectives for resource use and climate adaptations in northern Ghana

    DEFF Research Database (Denmark)

    Heve, William K; Olesen, Jørgen Eivind; Chirinda, Ngonidzashe

    2016-01-01

    Since soil organic matter (SOM) buffers against impacts of climatic variability, the objective of this study was to assess on-farm distribution of SOM and propose realistic options for increasing SOM and thus the adaptation of smallholder farmers to climate change and variability in the interior...... northern savannah of Ghana. Data and information on spatial distribution of soil organic carbon (SOC), current practices that could enhance climate adaptation including management of organic resources were collected through biophysical assessments and snap community surveys. Even though homestead fields...... and residues, traditions for bush-burning and competing use of organic resources for fuels. Our findings suggest a need for effective management practices, training and awareness aimed at improving management of organic resources and, consequently, increasing SOC and resilience to climate-change-induced risks....

  7. Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules.

    Science.gov (United States)

    Toshima, Kazunobu

    2013-05-01

    Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

  8. Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans.

    Science.gov (United States)

    Müller-Deile, Janina; Gellrich, Finn; Schenk, Heiko; Schroder, Patricia; Nyström, Jenny; Lorenzen, Johan; Haller, Hermann; Schiffer, Mario

    2016-01-01

    TGF-β is known as an important stress factor of podocytes in glomerular diseases. Apart from activation of direct pro-apoptotic pathways we wanted to analyze micro-RNA (miRs) driven regulation of components involved in the integrity of the glomerular filtration barrier induced by TGF-β. Since miR-143-3p (miR-143) is described as a TGF-β inducible miR in other cell types, we examined this specific miR and its ability to induce glomerular pathology. We analyzed miR-143 expression in cultured human podocytes after stimulation with TGF-β. We also microinjected zebrafish eggs with a miR-143 mimic or with morpholinos specific for its targets syndecan and versican and compared phenotype and proteinuria development. We detected a time dependent, TGF-β inducible expression of miR-143 in human podocytes. Targets of miR-143 relevant in glomerular biology are syndecans and versican, which are known components of the glycocalyx. We found that syndecan 1 and 4 were predominantly expressed in podocytes while syndecan 3 was largely expressed in glomerular endothelial cells. Versican could be detected in both cell types. After injection of a miR-143 mimic in zebrafish larvae, syndecan 3, 4 and versican were significantly downregulated. Moreover, miR-143 overexpression or versican knockdown by morpholino caused loss of plasma proteins, edema, podocyte effacement and endothelial damage. In contrast, knockdown of syndecan 3 and syndecan 4 had no effects on glomerular filtration barrier. Expression of versican and syndecan isoforms is indispensable for proper barrier function. Podocyte-derived miR-143 is a mediator for paracrine and autocrine cross talk between podocytes and glomerular endothelial cells and can alter expression of glomerular glycocalyx proteins. © 2016 The Author(s) Published by S. Karger AG, Basel.

  9. Organizations

    DEFF Research Database (Denmark)

    Hatch, Mary Jo

    Most of us recognize that organizations are everywhere. You meet them on every street corner in the form of families and shops, study in them, work for them, buy from them, pay taxes to them. But have you given much thought to where they came from, what they are today, and what they might become...... and considers many more. Mary Jo Hatch introduces the concept of organizations by presenting definitions and ideas drawn from the a variety of subject areas including the physical sciences, economics, sociology, psychology, anthropology, literature, and the visual and performing arts. Drawing on examples from...... prehistory and everyday life, from the animal kingdom as well as from business, government, and other formal organizations, Hatch provides a lively and thought provoking introduction to the process of organization....

  10. Organizations

    DEFF Research Database (Denmark)

    Hatch, Mary Jo

    and considers many more. Mary Jo Hatch introduces the concept of organizations by presenting definitions and ideas drawn from the a variety of subject areas including the physical sciences, economics, sociology, psychology, anthropology, literature, and the visual and performing arts. Drawing on examples from......Most of us recognize that organizations are everywhere. You meet them on every street corner in the form of families and shops, study in them, work for them, buy from them, pay taxes to them. But have you given much thought to where they came from, what they are today, and what they might become...... prehistory and everyday life, from the animal kingdom as well as from business, government, and other formal organizations, Hatch provides a lively and thought provoking introduction to the process of organization....

  11. Colorimetric detection of genetically modified organisms based on exonuclease III-assisted target recycling and hemin/G-quadruplex DNAzyme amplification.

    Science.gov (United States)

    Zhang, Decai; Wang, Weijia; Dong, Qian; Huang, Yunxiu; Wen, Dongmei; Mu, Yuejing; Yuan, Yong

    2017-12-21

    An isothermal colorimetric method is described for amplified detection of the CaMV 35S promoter sequence in genetically modified organism (GMO). It is based on (a) target DNA-triggered unlabeled molecular beacon (UMB) termini binding, and (b) exonuclease III (Exo III)-assisted target recycling, and (c) hemin/G-quadruplex (DNAzyme) based signal amplification. The specific binding of target to the G-quadruplex sequence-locked UMB triggers the digestion of Exo III. This, in turn, releases an active G-quadruplex segment and target DNA for successive hybridization and cleavage. The Exo III impellent recycling of targets produces numerous G-quadruplex sequences. These further associate with hemin to form DNAzymes and hence will catalyze H 2 O 2 -mediated oxidation of the chromogenic enzyme substrate ABTS 2- causing the formation of a green colored product. This finding enables a sensitive colorimetric determination of GMO DNA (at an analytical wavelength of 420 nm) at concentrations as low as 0.23 nM. By taking advantage of isothermal incubation, this method does not require sophisticated equipment or complicated syntheses. Analyses can be performed within 90 min. The method also discriminates single base mismatches. In our perception, it has a wide scope in that it may be applied to the detection of many other GMOs. Graphical abstract An isothermal and sensitive colorimetric method is described for amplified detection of CaMV 35S promoter sequence in genetically modified organism (GMO). It is based on target DNA-triggered molecular beacon (UMB) termini-binding and exonuclease III assisted target recycling, and on hemin/G-quadruplex (DNAzyme) signal amplification.

  12. ICT, Education, and Visual Impairment.

    Science.gov (United States)

    Douglas, Graeme

    2001-01-01

    Reviews developments in the use of information and communications technology (ICT) in the education of children with visual impairments. Highlights include the population of children with visual impairments in the United Kingdom; and World Health Organization classification of disability as a criteria by which the relevance of ICT can be measured.…

  13. 2-periodic metal-organic frameworks (MOFs) as supermolecular building layers (SBLs) for making targeted 3-periodic MOFs

    KAUST Repository

    Eddaoudi, Mohamed

    2015-09-22

    Embodiments of the present disclosure provide for chemical assemblies, multidimensional metal-organic frameworks (MOFs), supermolecular building layers (SBLs), inorganic molecular building blocks (MBBs), organic MBBs (designed ligands), methods of making each, and methods of using each, and the like. In an embodiment, the composition can be used in catalysis, separations, gas storage, and drug delivery.

  14. Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space

    Science.gov (United States)

    Miao, Zhengqiang; Tan, Kaeling; Vyas, Valmik K.; Whiteway, Malcolm; Robbins, Nicole; Wong, Koon Ho; Cowen, Leah E.

    2018-01-01

    The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition. PMID:29590106

  15. Molecular docking and geographical information systems as tools to assess the potential impact of veterinary medicines on non-target organisms and the environment

    OpenAIRE

    Bowker, F.

    2015-01-01

    Veterinary medicines (VMs) from agricultural industry can enter the environment in a number of ways. This includes direct exposure through aquaculture, accidental spillage and disposal, and indirect entry by leaching from manure or runoff after treatment. Many compounds used in animal treatments have ecotoxic properties that may have chronic or sometimes lethal effects when they come into contact with non-target organisms. VMs enter the environment in mixtures, potentially having additive eff...

  16. Targeting of αv-Integrins in Stem/Progenitor Cells and Supportive Microenvironment Impairs Bone Metastasis in Human Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Geertje van der Horst

    2011-06-01

    Full Text Available Acquisition of an invasive phenotype by cancer cells is a requirement for bone metastasis. Transformed epithelial cells can switch to a motile, mesenchymal phenotype by epithelial-mesenchymal transition (EMT. Recently, it has been shown that EMT is functionally linked to prostate cancer stem cells, which are not only critically involved in prostate cancer maintenance but also in bone metastasis. We showed that treatment with the non-peptide αv-integrin antagonist GLPG0187 dose-dependently increased the E-cadherin/vimentin ratio, rendering the cells a more epithelial, sessile phenotype. In addition, GLPG0187 dose-dependently diminished the size of the aldehyde dehydrogenase high subpopulation of prostate cancer cells, suggesting that αv-integrin plays an important role in maintaining the prostate cancer stem/progenitor pool. Our data show that GLPG0187 is a potent inhibitor of osteoclastic bone resorption and angiogenesis in vitro and in vivo. Real-time bioluminescent imaging in preclinical models of prostate cancer demonstrated that blocking αv-integrins by GLPG0187 markedly reduced their metastatic tumor growth according to preventive and curative protocols. Bone tumor burden was significantly lower in the preventive protocol. In addition, the number of bone metastases/mouse was significantly inhibited. In the curative protocol, the progression of bone metastases and the formation of new bone metastases during the treatment period was significantly inhibited. In conclusion, we demonstrate that targeting of integrins by GLPG0187 can inhibit the de novo formation and progression of bone metastases in prostate cancer by antitumor (including inhibition of EMT and the size of the prostate cancer stem cell population, antiresorptive, and antiangiogenic mechanisms.

  17. DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target.

    Directory of Open Access Journals (Sweden)

    Rubén Soto-Acosta

    2017-04-01

    about the mechanisms involved in host lipid metabolism during DENV replicative cycle and identifies new potential antiviral targets for DENV replication.

  18. Classes of organic molecules targeted by a methanogenic microbial consortium grown on sedimentary rocks of various maturities

    Directory of Open Access Journals (Sweden)

    Margaux eMesle

    2015-06-01

    Full Text Available Organic-rich shales are populated by methanogenic consortia that are able to degrade the fossilized organic matter into methane gas. To identify the organic fraction effectively degraded, we have sequentially depleted two types of organic-rich rocks, shales and coal, at two different maturities, by successive solvent extractions to remove the most soluble fractions (maltenes and asphaltenes and isolate kerogen. We show the ability of the consortia to produce methane from all rock samples, including those containing the most refractory organic matter, i.e. the kerogen. Shales yielded higher methane production than lignite and coal. Mature rocks yielded more methane than immature rocks. Surprisingly, the efficiency of the consortia was not influenced by the removal of the easily biodegradable fractions contained in the maltenes and asphaltenes. This suggests that one of the limitations of organic matter degradation in situ may be the accessibility of the carbon and energy source. Indeed, bitumen has a colloidal structure that may limit the accessibility to asphaltenes in the bulk rock. Solvent extractions might favor the access to asphaltenes and kerogen by modifying the spatial organization of the molecules in the rock matrix.

  19. Classes of organic molecules targeted by a methanogenic microbial consortium grown on sedimentary rocks of various maturities.

    Science.gov (United States)

    Meslé, Margaux; Dromart, Gilles; Haeseler, Frank; Oger, Philippe M

    2015-01-01

    Organic-rich shales are populated by methanogenic consortia that are able to degrade the fossilized organic matter into methane gas. To identify the organic fraction effectively degraded, we have sequentially depleted two types of organic-rich sedimentary rocks, shale, and coal, at two different maturities, by successive solvent extractions to remove the most soluble fractions (maltenes and asphaltenes) and isolate kerogen. We show the ability of the consortia to produce methane from all rock samples, including those containing the most refractory organic matter, i.e., the kerogen. Shales yielded higher methane production than lignite and coal. Mature rocks yielded more methane than immature rocks. Surprisingly, the efficiency of the consortia was not influenced by the removal of the easily biodegradable fractions contained in the maltenes and asphaltenes. This suggests that one of the limitations of organic matter degradation in situ may be the accessibility to the carbon and energy source. Indeed, bitumen has a colloidal structure that may prevent the microbial consortia from reaching the asphaltenes in the bulk rock. Solvent extractions might favor the access to asphaltenes and kerogen by modifying the spatial organization of the molecules in the rock matrix.

  20. Effect of mild hypothermia combined with VitC and EPO therapy on target organ damage in children with neonatal asphyxia

    Directory of Open Access Journals (Sweden)

    Shu-Yun Wang

    2017-10-01

    Full Text Available Objective: To study the effect of mild hypothermia combined with vitamin C (VitC and erythropoietin (EPO therapy on target organ damage in children with neonatal asphyxia. Methods: Children with neonatal asphyxia who were treated in Taihe County People’s Hospital between April 2014 and February 2017 were selected and randomly divided into two groups, mild hypothermia group received mild hypothermia combined VitC and EPO therapy, and control group received VitC and EPO therapy. Serum levels of of target organ damage markers, oxidative stress indexes and apoptosis indexes were measured before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum NSE, H-FABP, cTnI, CysC, MDA, Caspase-3, PDCD5, sFas and sFasL levels of both groups of children were significantly lower than those before treatment while TAS, SOD, GSH and Bcl-2 levels were significantly higher than those before treatment, and serum NSE, H-FABP, cTnI, CysC, MDA, Caspase-3, PDCD5, sFas and sFasL levels of mild hypothermia group were significantly lower than those of control group while TAS, SOD, GSH and Bcl-2 levels were significantly higher than those of control group. Conclusion: Mild hypothermia combined with VitC and EPO therapy can reduce the target organ damage of children with neonatal asphyxia by inhibiting oxidative stress and apoptosis.

  1. Expression and mechanism of mammalian target of rapamycin in age-related renal cell senescence and organ aging.

    Science.gov (United States)

    Zhuo, Li; Cai, Guangyan; Liu, Fuyou; Fu, Bo; Liu, Weiping; Hong, Quan; Ma, Qiang; Peng, Youming; Wang, Jianzhong; Chen, Xiangmei

    2009-10-01

    The mammalian target of rapamycin (mTOR) is relevant to cell senescence and organismal aging. This study firstly showed that the level of mTOR expression increased with aging in rat kidneys, rat mesangial cells and WI-38 cells (P aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P aging, and that mTOR may promote cellular senescence by regulating the cell cycle through p21(WAF1/CIP1/SDI1), which might provide a new target for preventing renal aging.

  2. Nanofiber Enabled, Multi - Target Passive Sampling Device for Determination of the Freely Dissolved Sediment Pore Water Concentrations of Organic Contaminants

    Science.gov (United States)

    2016-06-01

    Concentrations of Organic Contaminants SERDP Project ER-2543 JUNE 2016 Dr. Andres Martinez Dr. David M. Cwiertny The University of Iowa...Soil Preparation and Uptake Experiments ................................................................................ 15 Contaminated Sediment...38 Contaminated Sediment Systems .......................................................................................... 41 Conclusions and

  3. The impact of sediment bioturbation by secondary organisms on metal bioavailability, bioaccumulation and toxicity to target organisms in benthic bioassays: Implications for sediment quality assessment

    International Nuclear Information System (INIS)

    Remaili, Timothy M.; Simpson, Stuart L.; Amato, Elvio D.; Spadaro, David A.; Jarolimek, Chad V.; Jolley, Dianne F.

    2016-01-01

    Bioturbation alters the properties of sediments and modifies contaminant bioavailability to benthic organisms. These naturally occurring disturbances are seldom considered during the assessment of sediment quality. We investigated how the presence (High bioturbation) and absence (Low bioturbation) of a strongly bioturbating amphipod within three different sediments influenced metal bioavailability, survival and bioaccumulation of metals to the bivalve Tellina deltoidalis. The concentrations of dissolved copper decreased and manganese increased with increased bioturbation. For copper a strong correlation was observed between increased bivalve survival (53–100%) and dissolved concentrations in the overlying water. Increased bioturbation intensity resulted in greater tissue concentrations for chromium and zinc in some test sediments. Overall, the results highlight the strong influence that the natural bioturbation activities from one organism may have on the risk contaminants pose to other organisms within the local environment. The characterisation of field-based exposure conditions concerning the biotic or abiotic resuspension of sediments and the rate of attenuation of released contaminants through dilution or readsorption may enable laboratory-based bioassay designs to be adapted to better match those of the assessed environment. - Highlights: • Bioturbation intensity modifies metal exposure and outcomes of sediment bioassays. • Sediment fluxes of Cu decrease and Mn and Zn increase with increased bioturbation. • Strong correlations between bioaccumulated and dissolved Cd, Cr, Pb, Zn, Cu and Ni. • Weak correlations between bioaccumulated and particulate metals. - This study investigated the impact of sediment bioturbation intensity on metal bioavailability and toxicity to aquatic organisms, and the implications of this to toxicity test design.

  4. The impact of sediment bioturbation by secondary organisms on metal bioavailability, bioaccumulation and toxicity to target organisms in benthic bioassays: Implications for sediment quality assessment.

    Science.gov (United States)

    Remaili, Timothy M; Simpson, Stuart L; Amato, Elvio D; Spadaro, David A; Jarolimek, Chad V; Jolley, Dianne F

    2016-01-01

    Bioturbation alters the properties of sediments and modifies contaminant bioavailability to benthic organisms. These naturally occurring disturbances are seldom considered during the assessment of sediment quality. We investigated how the presence (High bioturbation) and absence (Low bioturbation) of a strongly bioturbating amphipod within three different sediments influenced metal bioavailability, survival and bioaccumulation of metals to the bivalve Tellina deltoidalis. The concentrations of dissolved copper decreased and manganese increased with increased bioturbation. For copper a strong correlation was observed between increased bivalve survival (53-100%) and dissolved concentrations in the overlying water. Increased bioturbation intensity resulted in greater tissue concentrations for chromium and zinc in some test sediments. Overall, the results highlight the strong influence that the natural bioturbation activities from one organism may have on the risk contaminants pose to other organisms within the local environment. The characterisation of field-based exposure conditions concerning the biotic or abiotic resuspension of sediments and the rate of attenuation of released contaminants through dilution or readsorption may enable laboratory-based bioassay designs to be adapted to better match those of the assessed environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Effect of seed kernel aqueous extract from Annona squamosa against three mosquito vectors and its impact on non-target aquatic organisms

    Directory of Open Access Journals (Sweden)

    Ravichandran Ramanibai

    2016-09-01

    Full Text Available Objective: To evaluate the toxicity of Annona squamosa (A. squamosa aqueous (physiological saline seed soluble extract and its control of mosquito population. Methods: Ovicidal, larvicidal and pupicidal activity of A. squamosa crude soluble seed kernel extract was determined according to World Health Organization. The mortality of each mosquito stage was recorded after 24 h exposured to plant material. Toxicity assay was used to assess the non-target organisms with different concentrations according to Organisation for Economic Co-operation and Development. Results: The aqueous solubilized extracts of A. squamosa elicit the toxicity against all stages of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus, and the LC50 values against stages of egg, 1st-4th larvae were (1.45 and 1.26–2.5 mg/mL, (1.12 and 1.19–2.81 mg/ mL and (1.80 and 2.12–3.41 mg/mL respectively. The pupicidal activity also brought forth amended activity against all three mosquitoes species, and the LC50 values were consider to be 3.19, 2.42 and 4.47 mg/mL. Ultimately there was no mortality observed from non-target organism of Chironomus costatus. Conclusions: Based on the findings of the study, it suggests that the use of A. squamosa plant extract can act as an alternate insecticidal agents for controlling target mosquitoes without affecting the non-target aquatic insect. Further investigation to identify the active compounds and their mechanisms of action is recommended.

  6. Nano-Sized Secondary Organic Aerosol of Diesel Engine Exhaust Origin Impairs Olfactory-Based Spatial Learning Performance in Preweaning Mice

    Directory of Open Access Journals (Sweden)

    Tin-Tin Win-Shwe

    2015-06-01

    Full Text Available The aims of our present study were to establish a novel olfactory-based spatial learning test and to examine the effects of exposure to nano-sized diesel exhaust-origin secondary organic aerosol (SOA, a model environmental pollutant, on the learning performance in preweaning mice. Pregnant BALB/c mice were exposed to clean air, diesel exhaust (DE, or DE-origin SOA (DE-SOA from gestational day 14 to postnatal day (PND 10 in exposure chambers. On PND 11, the preweaning mice were examined by the olfactory-based spatial learning test. After completion of the spatial learning test, the hippocampus from each mouse was removed and examined for the expressions of neurological and immunological markers using real-time RT-PCR. In the test phase of the study, the mice exposed to DE or DE-SOA took a longer time to reach the target as compared to the control mice. The expression levels of neurological markers such as the N-methyl-d-aspartate (NMDA receptor subunits NR1 and NR2B, and of immunological markers such as TNF-α, COX2, and Iba1 were significantly increased in the hippocampi of the DE-SOA-exposed preweaning mice as compared to the control mice. Our results indicate that DE-SOA exposure in utero and in the neonatal period may affect the olfactory-based spatial learning behavior in preweaning mice by modulating the expressions of memory function–related pathway genes and inflammatory markers in the hippocampus.

  7. Nano-Sized Secondary Organic Aerosol of Diesel Engine Exhaust Origin Impairs Olfactory-Based Spatial Learning Performance in Preweaning Mice.

    Science.gov (United States)

    Win-Shwe, Tin-Tin; Kyi-Tha-Thu, Chaw; Moe, Yadanar; Maekawa, Fumihiko; Yanagisawa, Rie; Furuyama, Akiko; Tsukahara, Shinji; Fujitani, Yuji; Hirano, Seishiro

    2015-06-30

    The aims of our present study were to establish a novel olfactory-based spatial learning test and to examine the effects of exposure to nano-sized diesel exhaust-origin secondary organic aerosol (SOA), a model environmental pollutant, on the learning performance in preweaning mice. Pregnant BALB/c mice were exposed to clean air, diesel exhaust (DE), or DE-origin SOA (DE-SOA) from gestational day 14 to postnatal day (PND) 10 in exposure chambers. On PND 11, the preweaning mice were examined by the olfactory-based spatial learning test. After completion of the spatial learning test, the hippocampus from each mouse was removed and examined for the expressions of neurological and immunological markers using real-time RT-PCR. In the test phase of the study, the mice exposed to DE or DE-SOA took a longer time to reach the target as compared to the control mice. The expression levels of neurological markers such as the N -methyl-d-aspartate (NMDA) receptor subunits NR1 and NR2B, and of immunological markers such as TNF-α, COX2, and Iba1 were significantly increased in the hippocampi of the DE-SOA-exposed preweaning mice as compared to the control mice. Our results indicate that DE-SOA exposure in utero and in the neonatal period may affect the olfactory-based spatial learning behavior in preweaning mice by modulating the expressions of memory function-related pathway genes and inflammatory markers in the hippocampus.

  8. The use of statistical tools in field testing of putative effects of genetically modified plants on non-target organisms

    NARCIS (Netherlands)

    Semenov, Alexander V.; van Elsas, Jan Dirk; Glandorf, Debora C. M.; Schilthuizen, Menno; de Boer, Willem F.

    To fulfill existing guidelines, applicants that aim to place their genetically modified (GM) insect-resistant crop plants on the market are required to provide data from field experiments that address the potential impacts of the GM plants on nontarget organisms (NTO's). Such data may be based on

  9. A non-targeted metabolomic approach to identify food markers to support discrimination between organic and conventional tomato crops.

    Science.gov (United States)

    Martínez Bueno, María Jesús; Díaz-Galiano, Francisco José; Rajski, Łukasz; Cutillas, Víctor; Fernández-Alba, Amadeo R

    2018-04-20

    In the last decade, the consumption trend of organic food has increased dramatically worldwide. However, the lack of reliable chemical markers to discriminate between organic and conventional products makes this market susceptible to food fraud in products labeled as "organic". Metabolomic fingerprinting approach has been demonstrated as the best option for a full characterization of metabolome occurring in plants, since their pattern may reflect the impact of both endogenous and exogenous factors. In the present study, advanced technologies based on high performance liquid chromatography-high-resolution accurate mass spectrometry (HPLC-HRAMS) has been used for marker search in organic and conventional tomatoes grown in greenhouse under controlled agronomic conditions. The screening of unknown compounds comprised the retrospective analysis of all tomato samples throughout the studied period and data processing using databases (mzCloud, ChemSpider and PubChem). In addition, stable nitrogen isotope analysis (δ 15 N) was assessed as a possible indicator to support discrimination between both production systems using crop/fertilizer correlations. Pesticide residue analyses were also applied as a well-established way to evaluate the organic production. Finally, the evaluation by combined chemometric analysis of high-resolution accurate mass spectrometry (HRAMS) and δ 15 N data provided a robust classification model in accordance with the agricultural practices. Principal component analysis (PCA) showed a sample clustering according to farming systems and significant differences in the sample profile was observed for six bioactive components (L-tyrosyl-L-isoleucyl-L-threonyl-L-threonine, trilobatin, phloridzin, tomatine, phloretin and echinenone). Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Targeting the pains of food insecurity and malnutrition among internally displaced persons with nutrient synergy and analgesics in organ meat.

    Science.gov (United States)

    Fayemi, Peter O; Muchenje, Voster; Yetim, Hasan; Ahhmed, Abdulatef

    2018-02-01

    Living with pain is one of the distressing effects of food insecurity and malnutrition among millions of internally displaced persons (IDPs) worldwide. Vulnerability to emotional pain, metabolic imbalance, chronic illnesses and non-communicable diseases by IDPs are associated with stressed livelihood and restricted access to balanced diets in their camps. Tackling the complexity of issues related to internal displacement is challenging as 45% are globally trapped in protracted conditions. In this review, a diet-based intervention is proposed considering the potential benefits of nutrient synergy and analgesic constituents in organ meat. Providing an affordable, value added and well packaged nutrient dense diet is suggested to meet daily protein and micronutrient requirements from organ meat. Also, unlocking health-promoting bioactive substances and analgesics in restructured organ meat product is proposed as personalized dietary remedy to exert opioid bioactivity in food matrix. Exploiting the nutrient synergy of this animal by-product will not only improve the nutritional status or wellbeing but also raise the composite score of dietary diversity or food security index among IDPs by 2030. Copyright © 2016. Published by Elsevier Ltd.

  11. Relationship of plasma proadrenomedullin and cortisol levels with systemic inflammatory response and target organ damage in children with sepsis after burn

    Directory of Open Access Journals (Sweden)

    Xing Wei

    2017-08-01

    Full Text Available Objective: To study the relationship of plasma proadrenomedullin (pro-ADM and cortisol (Cor levels with systemic inflammatory response and target organ damage in children with sepsis after burn. Methods: A total of 30 children with sepsis after burn who were treated in the hospital between August 2014 and August 2016 were collected as observation group, and 30 normal children who received vaccination in the hospital during the same period were collected as normal control group. The pro-ADM and Cor levels in plasma as well as the levels of inflammatory factors, myocardial injury markers and intestinal barrier function indexes in serum of the two groups were determined. Pearson test was used to assess the correlation of plasma pro-ADM and Cor levels with systemic inflammatory response and target organ damage in patients with sepsis after burn. Results: Plasma pro-ADM and Cor levels in observation group were higher than those in normal control group. Serum inflammatory cytokines IL-1, IL-6, IL-10 and TNF-α levels in observation group were higher than those in normal control group; serum myocardial injury markers CK-MB, cTnⅠ and NT-proBNP levels were higher than those in normal control group; serum intestinal barrier function indexes ET, DAO and D-L levels were higher than those in normal control group. Conclusion: Plasma pro-ADM and Cor levels increase in patients with sepsis after burn, and are highly consistent with systemic inflammatory response and target organ injury.

  12. Network approach to understanding the organization of and the consequence of targeted leader removal on an end-oriented task.

    Science.gov (United States)

    Annagiri, Sumana; Kolay, Swetashree; Paul, Bishwarup; Sona, Chandan

    2017-06-01

    Relocation is an important event in the lives of several social insects whereby all colony members have to be transferred to a new nest when conditions in the old nest become unfavorable. In the current study, network tools were used to examine the organization of this goal-oriented task in the Indian queenless ant Diacamma indicum which relocate their colonies by means of tandem running. Individual ants were used as nodes and tandem runs as directed edges to construct unweighted networks. Network parameters were characterized in control relocations (CRs) and in relocations where the node with the highest outdegree, that is, the Maximum tandem leader (Max TL) was experimentally removed. These were then compared to 1) randomized networks, 2) simulated networks in which Max TL was removed, and 3) simulated networks with removal of a random leader. Not only was there complete recovery of the task, but the manner in which it was organized when Max TL was removed was comparable to CRs. The results obtained from our empirical study were significantly different from the results predicted by simulations of leader removal. At an individual level, the Max TL had a significantly higher outdegree than expected by chance alone and in her absence the substitute Max TL did comparable work. In addition, the position of the Max TL in the pathway of information flow was conserved in control and experimentally manipulated conditions. Understanding the organization of this critical event as more than the sum of individual interactions using network parameters allows us to appreciate the dynamic response of groups to perturbations.

  13. Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket

    DEFF Research Database (Denmark)

    Höpner, Sabine; Dickhaut, Katharina; Hofstätter, Maria

    2006-01-01

    immune responses by catalyzing the peptide loading of human class II MHC molecules HLA-DR. Here we show now that they achieve this by interacting with a defined binding site of the HLA-DR peptide receptor. Screening of a compound library revealed a set of adamantane derivatives that strongly accelerated...... the peptide loading rate. The effect was evident only for an allelic subset and strictly correlated with the presence of glycine at the dimorphic position beta86 of the HLA-DR molecule. The residue forms the floor of the conserved pocket P1, located in the peptide binding site of MHC molecule. Apparently......-susceptible" MHC molecules. As catalysts of antigen loading, compounds targeting P1 may be useful molecular tools to amplify the immune response. The observation, however, that the ligand repertoire can be affected through polymorphic sites form the outside may also imply that environmental factors could induce...

  14. Fabrication of nano-mosquitocides using chitosan from crab shells: Impact on non-target organisms in the aquatic environment.

    Science.gov (United States)

    Murugan, Kadarkarai; Anitha, Jaganathan; Dinesh, Devakumar; Suresh, Udaiyan; Rajaganesh, Rajapandian; Chandramohan, Balamurugan; Subramaniam, Jayapal; Paulpandi, Manickam; Vadivalagan, Chitravel; Amuthavalli, Pandiyan; Wang, Lan; Hwang, Jiang-Shiou; Wei, Hui; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Kumar, Suresh; Pugazhendy, Kannaiyan; Higuchi, Akon; Nicoletti, Marcello; Benelli, Giovanni

    2016-10-01

    Mosquitoes are arthropods of huge medical and veterinary relevance, since they vector pathogens and parasites of public health importance, including malaria, dengue and Zika virus. Currently, nanotechnology is considered a potential eco-friendly approach in mosquito control research. We proposed a novel method of biofabrication of silver nanoparticles (AgNP) using chitosan (Ch) from crab shells. Ch-AgNP nanocomposite was characterized by UV-vis spectroscopy, FTIR, SEM, EDX and XRD. Ch-AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi obtaining LC50 ranging from 3.18 ppm (I) to 6.54 ppm (pupae). The antibacterial properties of Ch-AgNP were proved against Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi, while no growth inhibition was reported in assays conducted on Proteus vulgaris. Concerning non-target effects, in standard laboratory considtions the predation efficiency of Danio rerio zebrafishes was 68.8% and 61.6% against I and II instar larvae of A. stephensi, respectively. In a Ch-AgNP-contaminated environment, fish predation was boosted to 89.5% and 77.3%, respectively. Quantitative analysis of antioxidant enzymes SOD, CAT and LPO from hepatopancreas of fresh water crabs Paratelphusa hydrodromous exposed for 16 days to a Ch-AgNP-contaminated aquatic environment were conducted. Notably, deleterious effects of Ch-AgNP contaminating aquatic enviroment on the non-target crab P. hydrodromous were observed, particularly when doses higher than 8-10ppm are tested. Overall, this research highlights the potential of Ch-AGNP for the development of newer control tools against young instar populations of malaria mosquitoes, also highlighting some risks concerned the employ of nanoparticles in aquatic environments. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Organic-inorganic nano-composite films for photonic applications made by multi-beam multi-target pulsed laser deposition with remote control of the plume directions

    Science.gov (United States)

    Darwish, Abdalla M.; Moore, Shaelynn; Mohammed, Aziz; Alexander, Deonte'; Bastian, Tyler; Dorlus, Wydglif; Sarkisov, Sergey S.; Patel, Darayas N.; Mele, Paolo; Koplitz, Brent

    2016-09-01

    the components of different nature, organic polymers and inorganic dopants, in the same target at a certain proportion and exposing them to the same laser beam not necessarily brings good quality nano-composite films. The laser pulse energy and wavelength cannot be optimized for each component individually. Also, the mixing proportion in the composite film is dictated by the initial proportion of the target and thus cannot be changed in the process. These limitations were removed in the recently proposed method of multi-beam and multi-target deposition (in its doublebeam/ dual-target variation) using a MAPLE polymer target and one inorganic target, each being concurrently exposed to laser beams of different wavelengths.5-14 Using the method, nano-composite films of polymer poly(methyl methacrylate) known as PMMA doped with a rare earth (RE) inorganic upconversion phosphor compounds were prepared. Also, a nano-composite film of thermoelectric film of inorganic aluminum-doped ZnO known as AZO was impregnated with PMMA nano-fillers with the purpose of improving electrical conductivity and thermoelectric performance.10, 14 The polymer target was a frozen (to a temperature of liquid nitrogen) PMMA solution in chlorobenzene exposed to a 1064- nm laser beam from a Q-switched Nd:YAG pulsed laser. The inorganic targets were the pellets made of the compressed micro-powders of highly efficient RE-doped NaYF4 or the sintered powder of AZO concurrently ablated with the

  16. GC/MS Based Non-target Screening of Organic Contaminants in River Indus and its Tributaries in Sindh (Pakistan

    Directory of Open Access Journals (Sweden)

    Huma Shaikh1

    2014-06-01

    Full Text Available To investigate presence of organic contaminants in river Indus and its tributaries screening studies were carried out. Two years screening studies were based on four sampling campaigns in 13 sampling points out of which 9 sampling points belong to river Indus and its tributaries, 4 to municipal sewerage and 1 to industrial sewerage. Deconvolution Reporting Software (DRS was used to analyze scan data. Deconvolution is capable of screening the compounds whose peaks become invisible due to co-extracted compounds. Furthermore it significantly reduces analysis time and chromatographic resolution requirements. Results reveal that all the sampling points were greatly polluted with phthalate esters and tributyl phosphate (TBP. Apart from these, numerous long chain hydrocarbons, toxic phenols i.e. bisphenol A, analgesic i.e. ibuprofen and mefenamic acid, pesticides i.e. endosulfan, PCPIs, etc have significantly contaminated water bodies. In this screening analysis many compounds are identified that can be possible emerging contaminants and that are rarely documented. The identified contaminants are debated in accordance with their use, possible emission source and pathway. To the best of our knowledge this study holds first detailed screening of organic contaminants in river Indus and its tributaries. The information gathered in this analysis can be useful for future studies based on individual contamination in river Indus.

  17. Mycolactone diffuses from Mycobacterium ulcerans-infected tissues and targets mononuclear cells in peripheral blood and lymphoid organs.

    Directory of Open Access Journals (Sweden)

    Hui Hong

    Full Text Available Buruli ulcer (BU is a progressive disease of subcutaneous tissues caused by Mycobacterium ulcerans. The pathology of BU lesions is associated with the local production of a diffusible substance, mycolactone, with cytocidal and immunosuppressive properties. The defective inflammatory responses in BU lesions reflect these biological properties of the toxin. However, whether mycolactone diffuses from infected tissues and suppresses IFN-gamma responses in BU patients remains unclear.Here we have investigated the pharmacodistribution of mycolactone following injection in animal models by tracing a radiolabeled form of the toxin, and by directly quantifying mycolactone in lipid extracts from internal organs and cell subpopulations. We show that subcutaneously delivered mycolactone diffused into mouse peripheral blood and accumulated in internal organs with a particular tropism for the spleen. When mice were infected subcutaneously with M. ulcerans, this led to a comparable pattern of distribution of mycolactone. No evidence that mycolactone circulated in blood serum during infection could be demonstrated. However, structurally intact toxin was identified in the mononuclear cells of blood, lymph nodes and spleen several weeks before ulcerative lesions appear. Importantly, diffusion of mycolactone into the blood of M. ulcerans-infected mice coincided with alterations in the functions of circulating lymphocytes.In addition to providing the first evidence that mycolactone diffuses beyond the site of M. ulcerans infection, our results support the hypothesis that the toxin exerts immunosuppressive effects at the systemic level. Furthermore, they suggest that assays based on mycolactone detection in circulating blood cells may be considered for diagnostic tests of early disease.

  18. Actin re-organization induced by Chlamydia trachomatis serovar D--evidence for a critical role of the effector protein CT166 targeting Rac.

    Directory of Open Access Journals (Sweden)

    Jessica Thalmann

    Full Text Available The intracellular bacterium Chlamydia trachomatis causes infections of urogenital tract, eyes or lungs. Alignment reveals homology of CT166, a putative effector protein of urogenital C. trachomatis serovars, with the N-terminal glucosyltransferase domain of clostridial glucosylating toxins (CGTs. CGTs contain an essential DXD-motif and mono-glucosylate GTP-binding proteins of the Rho/Ras families, the master regulators of the actin cytoskeleton. CT166 is preformed in elementary bodies of C. trachomatis D and is detected in the host-cell shortly after infection. Infection with high MOI of C. trachomatis serovar D containing the CT166 ORF induces actin re-organization resulting in cell rounding and a decreased cell diameter. A comparable phenotype was observed in HeLa cells treated with the Rho-GTPase-glucosylating Toxin B from Clostridium difficile (TcdB or HeLa cells ectopically expressing CT166. CT166 with a mutated DXD-motif (CT166-mut exhibited almost unchanged actin dynamics, suggesting that CT166-induced actin re-organization depends on the glucosyltransferase motif of CT166. The cytotoxic necrotizing factor 1 (CNF1 from E. coli deamidates and thereby activates Rho-GTPases and transiently protects them against TcdB-induced glucosylation. CNF1-treated cells were found to be protected from TcdB- and CT166-induced actin re-organization. CNF1 treatment as well as ectopic expression of non-glucosylable Rac1-G12V, but not RhoA-G14A, reverted CT166-induced actin re-organization, suggesting that CT166-induced actin re-organization depends on the glucosylation of Rac1. In accordance, over-expression of CT166-mut diminished TcdB induced cell rounding, suggesting shared substrates. Cell rounding induced by high MOI infection with C. trachomatis D was reduced in cells expressing CT166-mut or Rac1-G12V, and in CNF1 treated cells. These observations indicate that the cytopathic effect of C. trachomatis D is mediated by CT166 induced Rac1 glucosylation

  19. Extended anaerobic conditions in the biological wastewater treatment: Higher reduction of toxicity compared to target organic micropollutants.

    Science.gov (United States)

    Völker, Johannes; Vogt, Tobias; Castronovo, Sandro; Wick, Arne; Ternes, Thomas A; Joss, Adriano; Oehlmann, Jörg; Wagner, Martin

    2017-06-01

    Extended anaerobic conditions during biological wastewater treatment may enhance the biodegradation of micropollutants. To explore this, we combined iron-reducing or substrate-limited anaerobic conditions and aerobic pilot-scale reactors directly at a wastewater treatment plant. To investigate the detoxification by these processes, we applied two in vitro bioassays for baseline toxicity (Microtox) and reactive toxicity (AREc32) as well as in vivo bioassays with aquatic model species in two laboratory experiments (Desmodesmus subspicatus, Daphnia magna) and two on-site, flow-through experiments (Potamopyrgus antipodarum, Lumbriculus variegatus). Moreover, we analyzed 31 commonly occurring micropollutants and 10 metabolites. The baseline toxicity of raw wastewater was effectively removed in full-scale and reactor scale activated sludge treatment (>85%), while the oxidative stress response was only partially removed (>61%). A combination of an anaerobic pre-treatment under iron reducing conditions and an aerobic nitrification significantly further reduced the residual in vitro toxicities by 46-60% and outperformed the second combination consisting of an aerobic pre-treatment and an anaerobic post-treatment under substrate-limiting conditions (27-43%). Exposure to effluents of the activated sludge treatment did not induce adverse in vivo effects in aquatic invertebrates. Accordingly, no further improvement in water quality could be observed. Compared to that, the removal of persistent micropollutants was increased. However, this observation was restricted to a limited number of compounds and the removal of the sum concentration of all target micropollutants was relative low (14-17%). In conclusion, combinations of strictly anaerobic and aerobic processes significantly enhanced the removal of specific and non-specific in vitro toxicities. Thus, an optimization of biological wastewater treatment can lead to a substantially improved detoxification. These otherwise

  20. Feasibility of reaching world health organization targets for hepatitis C and the cost-effectiveness of alternative strategies.

    Science.gov (United States)

    Wisløff, Torbjørn; White, Richard; Dalgard, Olav; Amundsen, Ellen J; Meijerink, Hinta; Kløvstad, Hilde

    2018-04-06

    New drugs for treating hepatitis C have considerably increased the probability of being cured. Treatment uptake, however, is still low. The objectives of this study were to analyse the impact of initiatives that may increase the proportion of infected people on treatment and interventions aimed at reducing the incidence of new infection among people who inject drugs. A compartmental model for Norway was used to simulate hepatitis C and related complications. We analysed two different screening initiatives aimed to increase the proportion of infected people on treatment. Interventions aiming at reducing the hepatitis C incidence analysed were opioid substitution therapy, a clean needle and syringe programme and a combination of both.The most cost-effective strategy for increasing hepatitis C treatment uptake was screening by general practitioners while simultaneously allowing for all infected people to be treated. We estimated that this intervention reduce the incidence of hepatitis C by 2030 by 63% compared to the current incidence. The two harm-reduction strategies both reduced the incidence of hepatitis C by about 70%. Combining an increase of the current clean needles and syringe programme with opioid substitution therapy was clearly the most cost-effective option. This strategy would reduce the incidence of hepatitis C by 80% compared to the current incidence by 2030. Thus, interventions to reduce the burden and spread of hepatitis C are cost-effective. Reaching the WHO target of a 90% reduction in hepatitis C incidence by 2030 may be difficult without combining different initiatives. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Genetically modified crops and aquatic ecosystems: considerations for environmental risk assessment and non-target organism testing.

    Science.gov (United States)

    Carstens, Keri; Anderson, Jennifer; Bachman, Pamela; De Schrijver, Adinda; Dively, Galen; Federici, Brian; Hamer, Mick; Gielkens, Marco; Jensen, Peter; Lamp, William; Rauschen, Stefan; Ridley, Geoff; Romeis, Jörg; Waggoner, Annabel

    2012-08-01

    Environmental risk assessments (ERA) support regulatory decisions for the commercial cultivation of genetically modified (GM) crops. The ERA for terrestrial agroecosystems is well-developed, whereas guidance for ERA of GM crops in aquatic ecosystems is not as well-defined. The purpose of this document is to demonstrate how comprehensive problem formulation can be used to develop a conceptual model and to identify potential exposure pathways, using Bacillus thuringiensis (Bt) maize as a case study. Within problem formulation, the insecticidal trait, the crop, the receiving environment, and protection goals were characterized, and a conceptual model was developed to identify routes through which aquatic organisms may be exposed to insecticidal proteins in maize tissue. Following a tiered approach for exposure assessment, worst-case exposures were estimated using standardized models, and factors mitigating exposure were described. Based on exposure estimates, shredders were identified as the functional group most likely to be exposed to insecticidal proteins. However, even using worst-case assumptions, the exposure of shredders to Bt maize was low and studies supporting the current risk assessments were deemed adequate. Determining if early tier toxicity studies are necessary to inform the risk assessment for a specific GM crop should be done on a case by case basis, and should be guided by thorough problem formulation and exposure assessment. The processes used to develop the Bt maize case study are intended to serve as a model for performing risk assessments on future traits and crops.

  2. [Analysis of Environmental-Stress-Related Impairments of Inner Ear].

    Science.gov (United States)

    Ohgami, Nobutaka; Iida, Machiko; Omata, Yasuhiro; Nakano, Chihiro; Wenting, Wu; Li, Xiang; Kato, Masashi

    2015-01-01

    Noise stress generated in industry is one of the environmental factors that physically affects the functions of the inner ear. Exposure to noise can cause hearing loss, resulting in serious problems in occupational and daily life. At present, however, there are very limited ways to prevent hearing impairments. The inner ear consists of the organ of Corti, vestibule and semicircular canal. Functional or morphological damage of these tissues in the inner ear caused by genetic factors, aging or environmental factors can result in hearing or balance impairments. In this review, we first introduce a deafness-related molecule found by our clinical research. Our experimental research using genetically engineered mice further demonstrated that impaired activity of the target molecule caused congenital and age-related hearing loss with neurodegeneration of spiral ganglion neurons in the inner ears. We also describe impaired balance in mice caused by exposure to low-frequency noise under experimental conditions with indoor environmental monitoring. We believe that our approaches to pursue both experimental research and fieldwork research complementarily are crucial for the development of a method for prevention of impairments of the inner ear.

  3. Loggerhead sea turtles (Caretta caretta): A target species for monitoring litter ingested by marine organisms in the Mediterranean Sea.

    Science.gov (United States)

    Matiddi, Marco; Hochsheid, Sandra; Camedda, Andrea; Baini, Matteo; Cocumelli, Cristiano; Serena, Fabrizio; Tomassetti, Paolo; Travaglini, Andrea; Marra, Stefano; Campani, Tommaso; Scholl, Francesco; Mancusi, Cecilia; Amato, Ezio; Briguglio, Paolo; Maffucci, Fulvio; Fossi, Maria Cristina; Bentivegna, Flegra; de Lucia, Giuseppe Andrea

    2017-11-01

    Marine litter is any persistent, manufactured or processed solid material discarded, disposed of or abandoned in the marine and coastal environment. Ingestion of marine litter can have lethal and sub-lethal effects on wildlife that accidentally ingests it, and sea turtles are particularly susceptible to this threat. The European Commission drafted the 2008/56/EC Marine Strategy Framework Directive with the aim to achieve a Good Environmental Status (GES), and the loggerhead sea turtle (Caretta caretta, Linnaeus 1758) was selected for monitoring the amount and composition of litter ingested by marine animals. An analogous decision has been made under the UNEP/MAP Barcelona Convention for the protection of the Mediterranean Sea, following the Ecosystem Approach. This work provides for the first time, two possible scenarios for the Marine Strategy Framework Directive GES, both related to "Trends in the amount and composition of litter ingested by marine animals" in the Mediterranean Sea. The study validates the use of the loggerhead turtle as target indicator for monitoring the impact of litter on marine biota and calls for immediate use of this protocol throughout the Mediterranean basin and European Region. Both GES scenarios are relevant worldwide, where sea turtles and marine litter are present, for measuring the impact of ingested plastics and developing policy strategies to reduce it. In the period between 2011 and 2014, 150 loggerhead sea turtles, found dead, were collected from the Italian Coast, West Mediterranean Sea Sub-Region. The presence of marine litter was investigated using a standardized protocol for necropsies and lab analysis. The collected items were subdivided into 4 main categories, namely, IND-Industrial plastic, USE-User plastic, RUB-Non plastic rubbish, POL-Pollutants and 14 sub-categories, to detect local diversity. Eighty-five percent of the individuals considered (n = 120) were found to have ingested an average of 1.3 ± 0.2 g of

  4. Estimates of internal dose equivalent to 22 target organs for radionuclides occurring in routine releases from nuclear fuel-cycle facilities. Vol. 1

    International Nuclear Information System (INIS)

    Killough, G.G.; Dunning, D.E. Jr.; Bernard, S.R.; Pleasant, J.C.

    1978-01-01

    This report is the first of a two-volume tabulation of internal radiation dose conversion factors for man for radionuclides of interest in environmental assessments of light-water-reactor fuel cycles. This volume treats 68 radionuclides, all of mass number less than 150. Intake by inhalation and ingestion is considered. In the former case, the ICRP Task Group Lung Model has been used to simulate the behavior of particulate matter in the respiratory tract. Results corresponding to activity median aerodynamic diameters (AMAD) of 0.3, 1.0, and 5.0 μm are given. The GI tract has been represented by a four-segment catenary model with exponential transfer of radioactivity from one segment to the next. Retention of radionuclides in other organs was characterized by linear combinations of decaying exponential functions. Dose equivalent per microcurie intake of each parent nuclide is given for 22 target organs with contributions from specified source organs plus surplus activity in the rest of the body. Cross irradiation due to penetrating radiations has also been considered in the calculations

  5. Assessment of biological effects of environmental pollution in Mersin Bay (Turkey, northeastern Mediterranean Sea) using Mullus barbatus and Liza ramada as target organisms

    International Nuclear Information System (INIS)

    Yılmaz, Doruk; Kalay, Mustafa; Dönmez, Erdem; Yılmaz, Nejat

    2016-01-01

    The increasing emphasis on the assessment and monitoring of marine ecosystems has revealed the need to use appropriate biological indicators for these areas. Enzyme activities and histopathology are increasingly being used as indicators of environmental stress since they provide a definite biological end-point of pollutant exposure. As part of an ecotoxicological assessment of Mersin Bay, EROD enzyme activity and histopathological response in selected organs and tissues of two species of fish, Mullus barbatus (red mullet) and Liza ramada (thinlip grey mullet), captured from area were examined. Pollutant (Organochlorines (OC), alkylphenols (APs) and BPA) levels and biomarker responses in tissue samples were evaluated together for their potential to alter the metabolism and cellular aspects in liver and gonad. Elevated induction of EROD activity and histopathological alterations in contaminated samples from Mersin Bay was observed compared to reference site indicating the exposure to potential pollutants. - Highlights: • PCBs, DDTs, APs and BPA were detected in liver tissues of red mullet (Mullus barbatus) and thinlip grey mullet (Liza ramada). • Highly induced EROD activity were measured in fish samples from Mersin Bay in comparison to reference fish. • Liver and gonad impairments were observed in samples from contaminated area of Mersin Bay. - Histopathological alterations and induced EROD activities were observed in parallel with elevated tissue concentrations of contaminants in red mullet and thinlip grey mullet.

  6. Temperament-Based Learning Styles of Visually Impaired Students.

    Science.gov (United States)

    Oakland, Thomas; Banner, Diane; Livingston, Rita

    2000-01-01

    A study investigated the learning style preferences of 214 students (ages 10-17) with visual impairments and their sighted peers. Students with visual impairments more frequently preferred practical, thinking, or organized styles. Boys with visual impairments tended to prefer extroverted styles and girls with visual impairments tended to prefer…

  7. Visual impairment in the hearing impaired students

    OpenAIRE

    Gogate Parikshit; Rishikeshi Nikhil; Mehata Reshma; Ranade Satish; Kharat Jitesh; Deshpande Madan

    2009-01-01

    Background : Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim : To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design : Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods : Hearing-impaired children in selected schools underwent detailed vis...

  8. Changes of serum pancreatic stone protein and cholinesterase contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage

    Directory of Open Access Journals (Sweden)

    Zhi-Hong Ren

    2017-10-01

    Full Text Available Objective: To study the changes of serum pancreatic stone protein (PSP and cholinesterase (ChE contents in children with sepsis and their correlation with systemic inflammatory response and target organ damage. Methods: A total of 64 children with sepsis who were treated in the hospital between January 2015 and January 2017 were selected as observation group, and 50 healthy children who received vaccination in the hospital during the same period were selected as normal control group. The contents of PSP, ChE, inflammatory factors as well as liver and kidney function indexes in the two groups were detected. Pearson test was used to assess the correlation of serum PSP and ChE contents with systemic inflammatory response and target organ damage in children with sepsis. Results: Serum PSP content of observation group was higher than that of control group while ChE content was lower than that of control group; serum inflammatory factors PCT, CRP, IL-1, IL-6 and IL-10 contents of observation group were higher than those of normal control group; liver function indexes TBIL, ALT and AST contents were higher than those of normal control group; kidney function indexes Scr and BUN contents were higher than those of normal control group. Pearson test showed that the serum PSP and ChE contents in children with sepsis were directly correlated with the systemic inflammatory response as well as liver and renal function injury. Conclusion: Serum PSP content significantly increases while ChE content significantly decreases in children with sepsis and the specific change is directly correlated with the overall disease severity.

  9. Step-and-Shoot versus Compensator-based IMRT: Calculation and Comparison of Integral Dose in Non-tumoral and Target Organs in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Kaveh Shirani Tak Abi

    2015-05-01

    Full Text Available Introduction Intensity-Modulated Radiotherapy (IMRT is becoming an increasingly routine treatment method. IMRT can be delivered by use of conventional Multileaf Collimators (MLCs and/or physical compensators. One of the most important factors in selecting an appropriate IMRT technique is integral dose. Integral dose is equal to the mean energy deposited in the total irradiated volume of the patient. The aim of the present study was to calculate and compare the integral dose in normal and target organs in two different procedures of IMRT: Step-and-Shoot (SAS and compensator-based IMRT. Materials and Methods In this comparative study, five patients with prostate cancer were selected. Module Integrated Radiotherapy System was applied, using three energy ranges. In both treatment planning methods, the integral dose dramatically decreased by increasing energy. Results Comparison of two treatment methods showed that on average, the integral dose of body in SAS radiation therapy was about 1.62% lower than that reported in compensator-based IMRT. In planning target volume, rectum, bladder, and left and right femoral heads, the integral doses for SAS method were 1.01%, 1.02%, 1.11%, 1.47%, and 1.40% lower than compensator-based IMRT, respectively. Conclusion Considering the treatment conditions, the definition of dose volume constraints for healthy tissues, and the equal volume of organs in both treatment methods, SAS radiation therapy by providing a lower integral dose seems to be more advantageous and efficient for prostate cancer treatment, compared to compensator-based IMRT.

  10. Development and validation of a multiplex real-time PCR method to simultaneously detect 47 targets for the identification of genetically modified organisms.

    Science.gov (United States)

    Cottenet, Geoffrey; Blancpain, Carine; Sonnard, Véronique; Chuah, Poh Fong

    2013-08-01

    Considering the increase of the total cultivated land area dedicated to genetically modified organisms (GMO), the consumers' perception toward GMO and the need to comply with various local GMO legislations, efficient and accurate analytical methods are needed for their detection and identification. Considered as the gold standard for GMO analysis, the real-time polymerase chain reaction (RTi-PCR) technology was optimised to produce a high-throughput GMO screening method. Based on simultaneous 24 multiplex RTi-PCR running on a ready-to-use 384-well plate, this new procedure allows the detection and identification of 47 targets on seven samples in duplicate. To comply with GMO analytical quality requirements, a negative and a positive control were analysed in parallel. In addition, an internal positive control was also included in each reaction well for the detection of potential PCR inhibition. Tested on non-GM materials, on different GM events and on proficiency test samples, the method offered high specificity and sensitivity with an absolute limit of detection between 1 and 16 copies depending on the target. Easy to use, fast and cost efficient, this multiplex approach fits the purpose of GMO testing laboratories.

  11. SU-E-T-287: Dose Verification On the Variation of Target Volume and Organ at Risk in Preradiation Chemotherapy IMRT for Nasopharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, X; Kong, L; Wang, J; Hu, W; Chen, Z [Fudan University Shanghai Cancer Center, Shanghai, Shanghai (China)

    2015-06-15

    Purpose: To quantify the target volume and organ at risk of nasopharyngeal carcinoma (NPC) patients with preradiation chemotherapy based on CT scanned during intensity-modulated radiotherapy (IMRT), and recalculate the dose distribution. Methods: Seven patients with NPC and preradiation chemotherapy, treated with IMRT (35 to 37 fractions) were reviewed. Repeat CT scanning was required to all of the patients during the radiotherapy, and the number of repeat CTs varies from 2 to 6. The plan CT and repeat CT were generated by different CT scanner. To ensure crespectively on the same IMPT plan. The real dose distribution was calculated by deformable registration and weighted method in Raystation (v 4.5.1). The fraction of each dose is based on radiotherapy record. The volumetric and dose differences among these images were calculated for nascIpharyngeal tumor and retro-pharyngeal lymph nodes (GTV-NX), neck lymph nodes(GTV-ND), and parotid glands. Results: The volume variation in GTV-NX from CT1 to CT2 was 1.15±3.79%, and in GTV-LN −0.23±4.93%. The volume variation in left parotid from CT1 to CT2 was −6.79±11.91%, and in right parotid −3.92±8.80%. In patient 2, the left parotid volume were decreased remarkably, as a Result, the V30 and V40 of it were increased as well. Conclusion: The target volume of patients with NPC varied lightly during IMRT. It shows that preradiation chemotherapy can control the target volume variation and perform a good dose repeatability. Also, the decreasing volume of parotid in some patient might increase the dose of it, which might course potential complications.

  12. Models of plasma membrane organization can be applied to mitochondrial membranes to target human health and disease with polyunsaturated fatty acids.

    Science.gov (United States)

    Raza Shaikh, Saame; Brown, David A

    2013-01-01

    Bioactive n-3 polyunsaturated fatty acids (PUFA), abundant in fish oil, have potential for treating symptoms associated with inflammatory and metabolic disorders; therefore, it is essential to determine their fundamental molecular mechanisms. Recently, several labs have demonstrated the n-3 PUFA docosahexaenoic acid (DHA) exerts anti-inflammatory effects by targeting the molecular organization of plasma membrane microdomains. Here we briefly review the evidence that DHA reorganizes the spatial distribution of microdomains in several model systems. We then emphasize how models on DHA and plasma membrane microdomains can be applied to mitochondrial membranes. We discuss the role of DHA acyl chains in regulating mitochondrial lipid-protein clustering, and how these changes alter several aspects of mitochondrial function. In particular, we summarize effects of DHA on mitochondrial respiration, electron leak, permeability transition, and mitochondrial calcium handling. Finally, we conclude by postulating future experiments that will augment our understanding of DHA-dependent membrane organization in health and disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Specific Language Impairment

    Science.gov (United States)

    ... Home » Health Info » Voice, Speech, and Language Specific Language Impairment On this page: What is specific language ... percent of children in kindergarten. What is specific language impairment? Specific language impairment (SLI) is a language ...

  14. Cortical Visual Impairment

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Cortical Visual Impairment En Español Read in Chinese What is cortical visual impairment? Cortical visual impairment (CVI) is a decreased ...

  15. All Vision Impairment

    Science.gov (United States)

    ... Prevalence Rates for Vision Impairment by Age and Race/Ethnicity Table for 2010 U.S. Age-Specific Prevalence ... Ethnicity 2010 Prevalence Rates of Vision Impairment by Race Table for 2010 Prevalence Rates of Vision Impairment ...

  16. Exposure of BALB/c Mice to Diesel Engine Exhaust Origin Secondary Organic Aerosol (DE-SOA) during the Developmental Stages Impairs the Social Behavior in Adult Life of the Males.

    Science.gov (United States)

    Win-Shwe, Tin-Tin; Kyi-Tha-Thu, Chaw; Moe, Yadanar; Fujitani, Yuji; Tsukahara, Shinji; Hirano, Seishiro

    2015-01-01

    Secondary organic aerosol (SOA) is a component of particulate matter (PM) 2.5 and formed in the atmosphere by oxidation of volatile organic compounds. Recently, we have reported that inhalation exposure to diesel engine exhaust (DE) originated SOA (DE-SOA) affect novel object recognition ability and impair maternal behavior in adult mice. However, it is not clear whether early life exposure to SOA during the developmental stages affect social behavior in adult life or not. In the present study, to investigate the effects of early life exposure to DE-SOA during the gestational and lactation stages on the social behavior in the adult life, BALB/c mice were exposed to clean air (control), DE, DE-SOA and gas without any PM in the inhalation chambers from gestational day 14 to postnatal day 21 for 5 h a day and 5 days per week. Then adult mice were examined for changes in their social behavior at the age of 13 week by a sociability and social novelty preference, social interaction with a juvenile mouse and light-dark transition test, hypothalamic mRNA expression levels of social behavior-related genes, estrogen receptor-alpha and oxytocin receptor as well as of the oxidative stress marker gene, heme oxygenase (HO)-1 by real-time RT-PCR method. In addition, hypothalamic level of neuronal excitatory marker, glutamate was determined by ELISA method. We observed that sociability and social novelty preference as well as social interaction were remarkably impaired, expression levels of estrogen receptor-alpha, oxytocin receptor mRNAs were significantly decreased, expression levels of HO-1 mRNAs and glutamate levels were significantly increased in adult male mice exposed to DE-SOA compared to the control ones. Findings of this study indicate early life exposure of BALB/c mice to DE-SOA may affect their late-onset hypothalamic expression of social behavior related genes, trigger neurotoxicity and impair social behavior in the males.

  17. Exposure of BALB/c mice to diesel engine exhaust origin secondary organic aer-osol (DE-SOA during the developmental stages impairs the social behavior in adult life of the males

    Directory of Open Access Journals (Sweden)

    Tin-Tin eWin-Shwe

    2016-01-01

    Full Text Available Secondary organic aerosol (SOA is a component of particulate matter (PM 2.5 and formed in the atmosphere by oxidation of volatile organic compounds. Recently, we have reported that inhalation exposure to diesel engine exhaust (DE originated SOA (DE-SOA affect novel object recognition ability and impair maternal behavior in adult mice. However, it is not clear whether early life exposure to SOA during the de-velopmental stages affect social behavior in adult life or not. In the present study, to investigate the effects of early life exposure to DE-SOA during the gestational and lactation stages on the social behavior in the adult life, BALB/c mice were exposed to clean air (control, DE, DE-SOA and gas without any particulate matter in the inhala-tion chambers from gestational day 14 to postnatal day 21 for 5 h a day and 5 days per week. Then adult mice were examined for changes in their social behavior at the age of 13 week by a sociability and social novelty preference, social interaction with a juvenile mouse and light-dark transition test, hypothalamic mRNA expression levels of social behavior-related genes, estrogen receptor-alpha and oxytocin receptor as well as of the oxidative stress marker gene, heme oxygenase (HO-1 by real-time RT-PCR method. In addition, hypothalamic level of neuronal excitatory marker, glutamate was determined by ELISA method. We observed that sociability and social novelty pref-erence as well as social interaction were remarkably impaired, expression levels of es-trogen receptor-alpha, oxytocin receptor mRNAs were significantly decreased, ex-pression levels of HO-1 mRNAs and glutamate levels were significantly increased in adult male mice exposed to DE-SOA compared to the control ones. Findings of this study indicate early life exposure of BALB/c mice to DE-SOA may affect their late-onset hypothalamic expression of social behavior related genes, trigger neurotoxi-city and impair social behavior in the males.

  18. Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response.

    Science.gov (United States)

    Liu, Qiang; Ma, Jian; Wang, Xue-Feng; Xiao, Fei; Li, Li-Jia; Zhang, Jiao-Er; Lin, Yue-Zhi; Du, Cheng; He, Xi-Jun; Wang, Xiaojun; Zhou, Jian-Hua

    2016-02-01

    The live equine infectious anemia virus (EIAV) vaccine strain EIAVDLV121 was developed by in vitro attenuation of a virulent strain, EIAVLN40, in the 1970s, and it has been demonstrated to induce protective immunity under laboratory and natural EIAV infection conditions. The detailed biological features of this attenuated virus remain to be further investigated. Experimental inoculation with EIAVDLV121 did not result in clinical symptoms even with immunosuppressive treatment in our previous studies. Here, we further investigated whether the replication of the vaccine strain EIAVDLV121 in experimentally infected horses causes histopathological lesions to develop in the targeted organs. Both the lungs and the spleen have been demonstrated to support EIAV replication. By evaluating the gross macroscopic and histological changes, we found that EIAVDLV121 did not cause detectable histopathological lesions and that it replicated several hundred times more slowly than its parental virulent strain, EIAVLN40, in tissues. Immunochemical assays of these tissues indicated that the primary target cells of EIAVDLV121 were monocytes/macrophages, but that EIAVLN40 also infected alveolar epithelial cells and vascular endothelial cells. In addition, both of these viral strains promoted the up- and down-regulation of the expression of various cytokines and chemokines, implicating the potential involvement of these cellular factors in the pathological outcomes of EIAV infection and host immune responses. Taken together, these results demonstrate that the EIAV vaccine strain does not cause obvious histopathological lesions or clinical symptoms and that it induces a unique cytokine response profile. These features are considered essential for EIAVDLV121 to function as an effective live vaccine. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The organization and evolution of the Responder satellite in species of the Drosophila melanogaster group: dynamic evolution of a target of meiotic drive.

    Science.gov (United States)

    Larracuente, Amanda M

    2014-11-25

    Satellite DNA can make up a substantial fraction of eukaryotic genomes and has roles in genome structure and chromosome segregation. The rapid evolution of satellite DNA can contribute to genomic instability and genetic incompatibilities between species. Despite its ubiquity and its contribution to genome evolution, we currently know little about the dynamics of satellite DNA evolution. The Responder (Rsp) satellite DNA family is found in the pericentric heterochromatin of chromosome 2 of Drosophila melanogaster. Rsp is well-known for being the target of Segregation Distorter (SD)- an autosomal meiotic drive system in D. melanogaster. I present an evolutionary genetic analysis of the Rsp family of repeats in D. melanogaster and its closely-related species in the melanogaster group (D. simulans, D. sechellia, D. mauritiana, D. erecta, and D. yakuba) using a combination of available BAC sequences, whole genome shotgun Sanger reads, Illumina short read deep sequencing, and fluorescence in situ hybridization. I show that Rsp repeats have euchromatic locations throughout the D. melanogaster genome, that Rsp arrays show evidence for concerted evolution, and that Rsp repeats exist outside of D. melanogaster, in the melanogaster group. The repeats in these species are considerably diverged at the sequence level compared to D. melanogaster, and have a strikingly different genomic distribution, even between closely-related sister taxa. The genomic organization of the Rsp repeat in the D. melanogaster genome is complex-it exists of large blocks of tandem repeats in the heterochromatin and small blocks of tandem repeats in the euchromatin. My discovery of heterochromatic Rsp-like sequences outside of D. melanogaster suggests that SD evolved after its target satellite and that the evolution of the Rsp satellite family is highly dynamic over a short evolutionary time scale (<240,000 years).

  20. 5C.07: A METHOD TO ESTIMATE 24-HOUR SODIUM EXCRETION THROUGH SPOT URINE SAMPLES AND ITS APPLICATION VALUE FOR TARGET-ORGAN DAMAGE ASSESSMENT.

    Science.gov (United States)

    Wang, H; Zhao, L; Xi, Y; Sun, N

    2015-06-01

    24-h urine sodium excretion is considered the most reliable method to evaluate the salt intakes. However, this method is cumbersome. So we want to develop formulas to estimate 24-h urinary sodium excretion using spot urinary samples in Chinese hypertensive population and explore the application value of this method in salt intake assessment and target organ damage. 1. We enrolled 510 cases of hospitalized patients with hypertension, 2/3 of them were arranged randomly to formula group to develop a new formula and the remainings were used to test the performance of the formula. All participants were instructed to collect a 24-h urine sample, a second morning voiding urine sample (SMU), and a post-meridiem urine sample in the late afternoon or early evening, prior to the evening meal (PMU). All samples were sent to measure sodium and creatinine concentration.2. We compared the differences of office blood pressure, 24-hour ambulatory blood pressure and left ventricular hypertrophy, vascular stiffness and urine protein among groups of different sodium intake. 24hour sodium excretion formulas was obtained using SMU and PMU respectively, which have good cosistency. The difference between the estimated and measured values in sodium excretion is 12.66mmol/day (SMU) and 9.41mmol/day (PM), to be equal to 0.7 g (SMU) and 0.6 g (PM) salt intake. Comparing with Kawasaki and Tanaka method, the new formula shows the lower degree of deviation, and higher accuracy and precision. Blood pressure of high urinary sodium group is higher than that in low urinary sodium group (P < 0.05). Left ventricular hypertrophy and urinary albumin/creatinine aggravated with the salt intake increase, this has eliminated the influence of other factors. All of morphologies of the relationship between ambulatory arterial stiffness index, pulse wave velocity and carotid intima-media thickness with quartiles of sodium intake resembled a J-shaped curve. In Chinese hypertensive population, the

  1. Carbon and silver nanoparticles in the fight against the filariasis vector Culex quinquefasciatus: genotoxicity and impact on behavioral traits of non-target aquatic organisms.

    Science.gov (United States)

    Murugan, Kadarkarai; Nataraj, Devaraj; Madhiyazhagan, Pari; Sujitha, Vasu; Chandramohan, Balamurugan; Panneerselvam, Chellasamy; Dinesh, Devakumar; Chandirasekar, Ramachandran; Kovendan, Kalimuthu; Suresh, Udaiyan; Subramaniam, Jayapal; Paulpandi, Manickam; Vadivalagan, Chithravel; Rajaganesh, Rajapandian; Wei, Hui; Syuhei, Ban; Aziz, Al Thabiani; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Nicoletti, Marcello; Canale, Angelo; Benelli, Giovanni

    2016-03-01

    Mosquito-borne diseases represent a deadly threat for millions of people worldwide. The Culex genus, with special reference to Culex quinquefasciatus, comprises the most common vectors of filariasis across urban and semi-urban areas of Asia. In recent years, important efforts have been conducted to propose green-synthesized nanoparticles as a valuable alternative to synthetic insecticides. However, the mosquitocidal potential of carbon nanoparticles has been scarcely investigated. In this study, the larvicidal and pupicidal activity of carbon nanoparticle (CNP) and silver nanoparticle (AgNP) was tested against Cx. quinquefasciatus. UV-Vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, and Raman analysis confirmed the rapid and cheap synthesis of carbon and silver nanoparticles. In laboratory assays, LC50 (lethal concentration that kills 50 % of the exposed organisms) values ranged from 8.752 ppm (first-instar larvae) to 18.676 ppm (pupae) for silver nanoparticles and from 6.373 ppm (first-instar larvae) to 14.849 ppm (pupae) for carbon nanoparticles. The predation efficiency of the water bug Lethocerus indicus after a single treatment with low doses of silver and carbon nanoparticles was not reduced. Moderate evidence of genotoxic effects induced by exposure to carbon nanoparticles was found on non-target goldfish, Carassius auratus. Lastly, the plant extract used for silver nanosynthesis was tested for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Overall, our results pointed out that AgNP and CNP can be a candidate for effective tools to reduce larval and pupal populations of filariasis vectors, with reduced genotoxicity and impact on behavioral traits of other aquatic organisms sharing the same ecological

  2. Impaired standing balance : unraveling the underlying cause in elderly

    NARCIS (Netherlands)

    Pasma, Jantsje Henrieke

    2015-01-01

    Impaired balance is often seen in elderly and can result in impaired mobility and finally in falling. Failure of compensation strategies or deterioration of underlying systems involved in standing balance could result in impaired balance. To apply targeted interventions to improve balance, it is

  3. WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Tichacek, Christopher J.; Tafreshi, Narges K.; Budzevich, Mikalai M.; Ruiz, Epifanio [Small Animal Imaging Core, Tampa, FL (United States); Wadas, Thaddeus J. [Wake Forest School of Medicine, Departments of Radiology and Cancer Biology, Winston-Salem, NC (United States); McLaughlin, Mark L. [Department of Chemistry, Tampa, FL (United States); H. Lee Moffitt Cancer Center & Research Institute (United States); Modulation Therapeutics, Inc., Tampa, FL (United States); Moros, Eduardo G.; Morse, David L.

    2016-06-15

    Purpose: The melanocortin-1 receptor (MC1R) is expressed in 94% of uveal melanomas and is described as an ideal target for this untreatable disease. MC1RL is a high affinity MC1R specific peptidomimetic ligand that can serve as a scaffold for therapeutic conjugates such as alpha particle emitting isotopes. The purpose of this study was to assess normal tissue distribution and risk as a result of using the DOTA chelator conjugated to MC1RL to deliver {sup 225}Ac: MC1RL-DOTA-{sup 225}Ac. Methods: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-{sup 225}Ac radiopharmaceutical with an average initial administered activity of 2.5 µCi. After the injection, three groups of animals (6, 6, and 5 per group) were euthanized at 24, 48, and 96 hour time points. A total of 11 organs of interest were harvested at each time point including kidneys and liver. Since the emitted alpha particles from {sup 225}Ac and its daughter products are not easy to detect directly, the isomeric gamma spectra were measured instead in the tissue samples using a modified Atomlab™ Gamma Counter (Biodex Medical Systems, Inc) and converted using factors for gamma ray abundance per alpha decay. Dosimetry was performed using measured radioactivity distribution in organs and the generalized internal dosimetry schema of MIRD pamphlet #21. Results: Our calculations have shown that the maximum absorbed dose was delivered to the liver with a total of 47 cGy per 96 hour period. The average dose per kidney was calculated to be 21 cGy. Heart, brain, lung, spleen, skin doses ranged from 0.01 to 1 cGy over the same time period. All animals gained weight over the 110 day decay period and no organ damage was observed by pathology. Conclusion: Based on our results, the risk of using the MC1RL-DOTA-{sup 225}Ac compound is relatively small in terms of deterministic radiation effects. Funding Support: NIH/NCI P50CA168536-03 Skin SPORE; NIH/NCI Phase I SBIR Contract #HHSN

  4. Systematic evaluation of MRI findings in different stages of treatment of cervical cancer: Potential of MRI on delineation of target, pathoanatomic structures, and organs at risk

    International Nuclear Information System (INIS)

    Dimopoulos, Johannes; Schard, Gerdi; Berger, Daniel; Lang, Stefan; Goldner, Gregor; Helbich, Thomas; Poetter, Richard

    2006-01-01

    Purpose: To compare magnetic resonance imaging (MRI) findings at different stages of cervix cancer treatment and to define the potential of MRI to delineate the gross tumor volume (GTV), clinical target volume (CTV), pathoanatomic structures, and organs at risk (OAR) in brachytherapy. Methods and Materials: Forty-nine patients underwent MRI at diagnosis and at brachytherapy. The ability to discriminate anatomic structures on MRI was assessed (quality factor: 0 = inability to discriminate; 1 = fair discrimination; 2 = good discrimination; 3 = excellent discrimination). The overall ability to visualize (percentage of patients with quality factors greater than 0) and the overall discrimination quality score (mean quality factors of all patients) were estimated for the applicator, GTV at diagnosis (GTV D ), GTV at brachytherapy (GTV BT )/'gray zones,' cervix rim/uterine corpus, OAR, vaginal wall, and parametria. Results: The overall ability to visualize the applicator on MRI at brachytherapy was 100%; for the GTV BT /'gray zones,' cervix rim/uterine corpus, OAR, and vaginal wall, visualization was 98% (overall discrimination quality factors: 1.2, 2.9, 2.1, 1.9, 1.7, and 2.6). Three of 4 borders of parametrial space were defined in more than 98% (discrimination quality factors: 2.9, 2.1, and 1.2). Conclusion: Magnetic resonance imaging provides appropriate information for definition of the applicator, GTV, CTV, pathoanatomic structures, and OAR that enables precise delineation for cervix cancer brachytherapy

  5. Differences in absorbed doses at risk organs and target tumoral of planning(PTV) in lung treatments using two algorithms of different calculations

    International Nuclear Information System (INIS)

    Uruena Llinares, A.; Santos Rubio, A.; Luis Simon, F. J.; Sanchez Carmona, G.; Herrador Cordoba, M.

    2006-01-01

    The objective of this paper is to compare, in thirty treatments for lung cancer,the absorbed doses at risk organs and target volumes obtained between the two used algorithms of calculation of our treatment planning system Oncentra Masterplan, that is, Pencil Beams vs Collapsed Cone. For it we use a set of measured indicators (D1 and D99 of tumor volume, V20 of lung, homogeneity index defined as (D5-D95)/D prescribed, and others). Analysing the dta, making a descriptor analysis of the results, and applying the non parametric test of the ranks with sign of Wilcoxon we find that the use of Pencil Beam algorithm underestimates the dose in the zone of the PTV including regions of low density as well as the values of maximum dose in spine cord. So, we conclude that in those treatments in which the spine dose is near the maximum permissible limit or those in which the PTV it includes a zone with pulmonary tissue must be used the Collapse Cone algorithm systematically and in any case an analysis must become to choose between time and precision in the calculation for both algorithms. (Authors)

  6. Valuing goodwill: not-for-profits prepare for annual impairment testing.

    Science.gov (United States)

    Heuer, Christian; Travers, Mary Ann K

    2011-02-01

    Accounting standards for valuing goodwill and intangible assets are becoming more rigorous for not-for-profit organizations: Not-for-profit healthcare organizations need to test for goodwill impairment at least annually. Impairment testing is a two-stage process: initial analysis to determine whether impairment exists and subsequent calculation of the magnitude of impairment. Certain "triggering" events compel all organizations--whether for-profit or not-for-profit--to perform an impairment test for goodwill or intangible assets.

  7. Transplantation and survival of mouse inner ear progenitor/stem cells in the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results

    Directory of Open Access Journals (Sweden)

    L.C.M. Barboza Jr.

    2016-01-01

    Full Text Available In mammals, damage to sensory receptor cells (hair cells of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350g were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4 received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4 received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy.

  8. Cortical visual impairment

    OpenAIRE

    Koželj, Urša

    2013-01-01

    In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

  9. Targeting beta- and alpha-adrenergic receptors differentially shifts Th1, Th2, and inflammatory cytokine profiles in immune organs to attenuate adjuvant arthritis

    Directory of Open Access Journals (Sweden)

    Dianne eLorton

    2014-08-01

    Full Text Available The sympathetic nervous system (SNS regulates host defense responses and restores homeostasis. SNS-immune regulation is altered in rheumatoid arthritis (RA and rodent models of RA, characterized by nerve remodeling in immune organs and defective adrenergic receptor (AR signaling to immune cell targets that typically promotes or suppresses inflammation via α- and β2-AR activation, respectively, and indirectly drives humoral immunity by blocking Th1 cytokine secretion. Here, we investigate how β2-AR stimulation and/or α-AR blockade at disease onset affects disease pathology and cytokine profiles in relevant immune organs from male Lewis rats with adjuvant-induced arthritis (AA. Rats challenged to induce AA were treated with terbutaline (TERB, a β2-AR agonist (600 μg/kg/day and/or phentolamine (PHEN, an α-AR antagonist (5.0 mg/kg/day or vehicle from disease onset through severe disease. We report that in spleen, mesenteric (MLN and draining lymph node (DLN cells, TERB reduces proliferation, an effect independent of IL-2. TERB also fails to shift Th cytokines from a Th1 to Th2 profile in spleen and MLN (no effect on IFN-γ and DLN (greater IFN-γ cells. In splenocytes, TERB, PHEN and co-treatment (PT promotes an anti-inflammatory profile (greater IL-10 and lowers TNF-α (PT only. In DLN cells, drug treatments do not affect inflammatory profiles, except PT, which raised IL-10. In MLN cells, TERB or PHEN lowers MLN cell secretion of TNF-α or IL-10, respectively. Collectively, our findings indicate disrupted β2-AR, but not α-AR signaling in AA. Aberrant β2-AR signaling consequently derails the sympathetic regulation of lymphocyte expansion, Th cell differentiation, and inflammation in the spleen, DLNs and MLNs that is required for immune system homeostasis. Importantly, this study provides potential mechanisms through which reestablished balance between α- and β2-AR function in the immune system ameliorates inflammation and joint

  10. Short-term blood pressure variability over 24 h and target organ damage in middle-aged men and women.

    LENUS (Irish Health Repository)

    Madden, J M

    2015-03-19

    Blood pressure variability (BPV) has been associated with cardiovascular events; however, the prognostic significance of short-term BPV remains uncertain. As uncertainty also remains as to which measure of variability most accurately describes short-term BPV, this study explores different indices and investigates their relationship with subclinical target organ damage (TOD). We used data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47-73 years (n=2047). A subsample (1207) underwent 24-h ambulatory BP monitoring (ABPM). As measures of short-term BPV, we estimated the s.d., weighted s.d. (wSD), coefficient of variation (CV) and average real variability (ARV). TOD was documented by microalbuminuria and electrocardiogram (ECG) left ventricular hypertrophy (LVH). There was no association found between any measure of BPV and LVH in both unadjusted and fully adjusted logistic regression models. Similar analysis found that ARV (24 h, day and night), s.d. (day and night) and wSD were all univariately associated with microalbuminuria and remained associated after adjustment for age, gender, smoking, body mass index (BMI), diabetes and antihypertensive treatment. However, when the models were further adjusted for the mean BP the association did not persist for all indices. Our findings illustrate choosing the appropriate summary measure, which accurately captures that short-term BPV is difficult. Despite discrepancies in values between the different measures, there was no association between any indexes of variability with TOD measures after adjustment for the mean BP.Journal of Human Hypertension advance online publication, 19 March 2015; doi:10.1038\\/jhh.2015.18.

  11. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets.

    Science.gov (United States)

    Bekhouche, Mourad; Leduc, Cedric; Dupont, Laura; Janssen, Lauriane; Delolme, Frederic; Vadon-Le Goff, Sandrine; Smargiasso, Nicolas; Baiwir, Dominique; Mazzucchelli, Gabriel; Zanella-Cleon, Isabelle; Dubail, Johanne; De Pauw, Edwin; Nusgens, Betty; Hulmes, David J S; Moali, Catherine; Colige, Alain

    2016-05-01

    A disintegrin and metalloproteinase with thrombospondin type I motif (ADAMTS)2, 3, and 14 are collectively named procollagen N-proteinases (pNPs) because of their specific ability to cleave the aminopropeptide of fibrillar procollagens. Several reports also indicate that they could be involved in other biological processes, such as blood coagulation, development, and male fertility, but the potential substrates associated with these activities remain unknown. Using the recently described N-terminal amine isotopic labeling of substrate approach, we analyzed the secretomes of human fibroblasts and identified 8, 17, and 22 candidate substrates for ADAMTS2, 3, and 14, respectively. Among these newly identified substrates, many are components of the extracellular matrix and/or proteins related to cell signaling such as latent TGF-β binding protein 1, TGF-β RIII, and dickkopf-related protein 3. Candidate substrates for the 3 ADAMTS have been biochemically validated in different contexts, and the implication of ADAMTS2 in the control of TGF-β activity has been further demonstrated in human fibroblasts. Finally, the cleavage site specificity was assessed showing a clear and unique preference for nonpolar or slightly hydrophobic amino acids. This work shows that the activities of the pNPs extend far beyond the classically reported processing of the aminopropeptide of fibrillar collagens and that they should now be considered as multilevel regulators of matrix deposition and remodeling.-Bekhouche, M., Leduc, C., Dupont, L., Janssen, L., Delolme, F., Vadon-Le Goff, S., Smargiasso, N., Baiwir, D., Mazzucchelli, G., Zanella-Cleon, I., Dubail, J., De Pauw, E., Nusgens, B., Hulmes, D. J. S., Moali, C., Colige, A. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets. © FASEB.

  12. Exposure to a sublethal concentration of imidacloprid and the side effects on target and nontarget organs of Apis mellifera (Hymenoptera, Apidae).

    Science.gov (United States)

    Catae, Aline Fernanda; Roat, Thaisa Cristina; Pratavieira, Marcel; Silva Menegasso, Anally Ribeiro da; Palma, Mario Sergio; Malaspina, Osmar

    2018-03-01

    The use of insecticides has become increasingly frequent, and studies indicate that these compounds are involved in the intoxication of bees. Imidacloprid is a widely used neonicotinoid; thus, we have highlighted the importance of assessing its oral toxicity to Africanized bees and used transmission electron microscopy to investigate the sublethal effects in the brain, the target organ, and the midgut, responsible for the digestion/absorption of food. In addition, the distribution of proteins involved in important biological processes in the brain were evaluated on the 1st day of exposure by MALDI-imaging analysis. Bioassays were performed to determine the Median Lethal Concentration (LC 50 ) of imidacloprid to bees, and the value obtained was 1.4651 ng imidacloprid/μL diet. Based on this result, the sublethal concentration to be administered at 1, 4 and 8 days was established as a hundredth (1/100) of the LC 50 . The results obtained from the ultrastructural analysis showed alterations in the midgut cells of bees as nuclear and mitochondrial damage and an increase of vacuoles. The insecticide caused spacing among the Kenyon cells in the mushroom bodies, chromatin condensation and loss of mitochondrial cristae. The MALDI-imaging analysis showed an increase in the expression of such proteins as vascular endothelial growth factor receptor, amyloid protein precursor and protein kinase C, which are related to oxygen supply, neuronal degeneration and memory/learning, and a decrease in the expression of the nicotinic acetylcholine receptor alpha 1, which is fundamental to the synapses. These alterations demonstrated that imidacloprid could compromise the viability of the midgut epithelium, as well as inhibiting important cognitive processes in individuals, and may be reflected in losses of the colony.

  13. The potential benefits from respiratory gating for breast cancer patients regarding target coverage and dose to organs at risk when applying strict dose limits to the heart: results from the DBCG HYPO trial

    DEFF Research Database (Denmark)

    Berg, Martin; Lorenzen, Ebbe L; Jensen, Ingelise

    2018-01-01

    PURPOSE: The potential benefits from respiratory gating (RG) compared to free-breathing (FB) regarding target coverage and dose to organs at risk for breast cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO multicentre trial are reported. MATERIAL AND METHODS: Patients i...

  14. Target cells in radiation pneumopathy

    International Nuclear Information System (INIS)

    Trott, Klaus Ruediger; Herrmann, Thomas; Kasper, Michael

    2004-01-01

    Radiation pneumopathy is the reaction of the organ lung to radiation effects in various target cells. It starts as an exudative inflammation, with the clinical picture of interstitial pneumonia 6-12 weeks after irradiation, and proceeds to a productive chronic inflammation lasting several months and terminating, as other chronic inflammations do, in scar formation, called lung fibrosis. Lung fibrosis is the common end point after lung damage from a wide range of damaging agents. The pathogenetic process leading to the signs and symptoms of radiation pneumopathy is an integrated response of the complex organization of lung tissue. Clinical and pathologic data in patients do not support the hypothesis that the early inflammatory phase of radiation 'pneumonitis' and late 'radiation fibrosis' are independent pathogenetic processes in the same way as acute radiodermatitis and subcutaneous fibrosis are separate pathologic entities. The target cell population that initiates the pathogenetic process in the lung is not known, and it has been suggested that no single identifiable target exists. The entire process is the result of complex functional alterations in endothelial cells, pneumocytes, macrophages, and other resident and transient cells. No evidence has been found for a role of stem cell sterilization, for impaired transit cell proliferation, or for hypoplasia, which is the hallmark of other acute inflammatory normal tissue damage (i.e., in the mucosa). The radiobiologic concepts developed in cellular radiobiology are not adequate for the quantitative analysis of radiation pneumopathy. A new analytical framework based on structurally defined intercellular interaction by signaling molecules and their activation needs to be developed. This would not be only an abstract radiobiologic paradigm but would be the key to the development of potential therapeutic interventions in irradiated patients

  15. Visual impairment in the hearing impaired students.

    Science.gov (United States)

    Gogate, Parikshit; Rishikeshi, Nikhil; Mehata, Reshma; Ranade, Satish; Kharat, Jitesh; Deshpande, Madan

    2009-01-01

    Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. To detect and treat visual impairment, if any, in hearing-impaired children. Observational, clinical case series of hearing-impaired children in schools providing special education. Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen's E charts. Refractive errors and squint were treated as per standard practice. Excel software was used for data entry and SSPS for analysis. The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24%) had ocular problems. Refractive errors were the most common morbidity 167(18.5%), but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3%) children, and retinal pigmentary dystrophy in five (0.6%) children. Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense.

  16. Differences in metabolic parameters and cardiovascular risk between American Diabetes Association and World Health Organization definition of impaired fasting glucose in European Caucasian subjects: a cross-sectional study.

    Science.gov (United States)

    Filippatos, Theodosios D; Rizos, Evangelos C; Gazi, Irene F; Lagos, Konstantinos; Agouridis, Dimitrios; Mikhailidis, Dimitri P; Elisaf, Moses S

    2013-10-31

    The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as fasting plasma glucose concentration of 100-125 mg/dl, whereas the World Health Organization (WHO) and the International Diabetes Federation (IDF) define IFG as fasting plasma glucose levels of 110-125 mg/dl. We identified differences in metabolic parameters and cardiovascular disease (CVD) risk according to the ADA or WHO/IDF definition of IFG. Healthy drug-naive Caucasian (Greek) subjects (n = 396; age 55 ±12 years) participated in this cross-sectional study. Diastolic blood pressure (DBP) and uric acid levels were higher in the subjects with glucose 100-109 mg/dl compared with those with glucose definition recognized subjects with significantly increased 10-year CVD risk estimation (SCORE risk calculation) compared with their respective controls (5.4% (IQR = 0.9-7.3) vs. 4.1% (IQR = 0.7-5.8), p = 0.002). The ADA IFG definition recognized more subjects with significantly increased CVD risk (SCORE model) compared with the WHO/IDF definition.

  17. Automatic segmentation of the clinical target volume and organs at risk in the planning CT for rectal cancer using deep dilated convolutional neural networks.

    Science.gov (United States)

    Men, Kuo; Dai, Jianrong; Li, Yexiong

    2017-12-01

    Delineation of the clinical target volume (CTV) and organs at risk (OARs) is very important for radiotherapy but is time-consuming and prone to inter-observer variation. Here, we proposed a novel deep dilated convolutional neural network (DDCNN)-based method for fast and consistent auto-segmentation of these structures. Our DDCNN method was an end-to-end architecture enabling fast training and testing. Specifically, it employed a novel multiple-scale convolutional architecture to extract multiple-scale context features in the early layers, which contain the original information on fine texture and boundaries and which are very useful for accurate auto-segmentation. In addition, it enlarged the receptive fields of dilated convolutions at the end of networks to capture complementary context features. Then, it replaced the fully connected layers with fully convolutional layers to achieve pixel-wise segmentation. We used data from 278 patients with rectal cancer for evaluation. The CTV and OARs were delineated and validated by senior radiation oncologists in the planning computed tomography (CT) images. A total of 218 patients chosen randomly were used for training, and the remaining 60 for validation. The Dice similarity coefficient (DSC) was used to measure segmentation accuracy. Performance was evaluated on segmentation of the CTV and OARs. In addition, the performance of DDCNN was compared with that of U-Net. The proposed DDCNN method outperformed the U-Net for all segmentations, and the average DSC value of DDCNN was 3.8% higher than that of U-Net. Mean DSC values of DDCNN were 87.7% for the CTV, 93.4% for the bladder, 92.1% for the left femoral head, 92.3% for the right femoral head, 65.3% for the intestine, and 61.8% for the colon. The test time was 45 s per patient for segmentation of all the CTV, bladder, left and right femoral heads, colon, and intestine. We also assessed our approaches and results with those in the literature: our system showed superior

  18. Mild Cognitive Impairment (MCI)

    Science.gov (United States)

    Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It can involve ...

  19. Mild Cognitive Impairment (MCI)

    Science.gov (United States)

    Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

  20. Epigenetic treatments for cognitive impairments.

    Science.gov (United States)

    Day, Jeremy J; Sweatt, J David

    2012-01-01

    Epigenetic mechanisms integrate signals from diverse intracellular transduction cascades and in turn regulate genetic readout. Accumulating evidence has revealed that these mechanisms are critical components of ongoing physiology and function in the adult nervous system, and are essential for many cognitive processes, including learning and memory. Moreover, a number of psychiatric disorders and syndromes that involve cognitive impairments are associated with altered epigenetic function. In this review, we will examine how epigenetic mechanisms contribute to cognition, consider how changes in these mechanisms may lead to cognitive impairments in a range of disorders and discuss the potential utility of therapeutic treatments that target epigenetic machinery. Finally, we will comment on a number of caveats associated with interpreting epigenetic changes and using epigenetic treatments, and suggest future directions for research in this area that will expand our understanding of the epigenetic changes underlying cognitive disorders.

  1. The effect of spatial organization of targets and distractors on the capacity to selectively memorize objects in visual short-term memory.

    Science.gov (United States)

    Abbes, Aymen Ben; Gavault, Emmanuelle; Ripoll, Thierry

    2014-01-01

    We conducted a series of experiments to explore how the spatial configuration of objects influences the selection and the processing of these objects in a visual short-term memory task. We designed a new experiment in which participants had to memorize 4 targets presented among 4 distractors. Targets were cued during the presentation of distractor objects. Their locations varied according to 4 spatial configurations. From the first to the last configuration, the distance between targets' locations was progressively increased. The results revealed a high capacity to select and memorize targets embedded among distractors even when targets were extremely distant from each other. This capacity is discussed in relation to the unitary conception of attention, models of split attention, and the competitive interaction model. Finally, we propose that the spatial dispersion of objects has different effects on attentional allocation and processing stages. Thus, when targets are extremely distant from each other, attentional allocation becomes more difficult while processing becomes easier. This finding implicates that these 2 aspects of attention need to be more clearly distinguished in future research.

  2. Memory Impairment in Children with Language Impairment

    Science.gov (United States)

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  3. Visual impairment in the hearing impaired students

    Directory of Open Access Journals (Sweden)

    Gogate Parikshit

    2009-01-01

    Full Text Available Background : Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim : To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design : Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods : Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen′s E charts. Refractive errors and squint were treated as per standard practice. Statistical Analysis : Excel software was used for data entry and SSPS for analysis. Results : The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24% had ocular problems. Refractive errors were the most common morbidity 167(18.5%, but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3% children, and retinal pigmentary dystrophy in five (0.6% children. Conclusion : Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense.

  4. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  5. A pilot prospective feasibility study of organ-at-risk definition using Target Contour Testing/Instructional Computer Software (TaCTICS), a training and evaluation platform for radiotherapy target delineation.

    Science.gov (United States)

    Kalpathy-Cramer, Jayashree; Bedrick, Steven D; Boccia, Kelly; Fuller, Clifton D

    2011-01-01

    Target volume delineation is a critical, but time-consuming step in the creation of radiation therapy plans used in the treatment of many types of cancer. However, variability in target volume definitions can introduce substantial differences in resulting doses to tumors and critical structures. We developed TaCTICS, a web-based educational training software application targeted towards non-expert users. We report on a small, prospective study to evaluate the utility of this online tool in improving conformance of regions-of-interest (ROIs) with a reference set. Eight residents contoured a set of structures for a head-and-neck cancer case. Subsequently, they were provided access to TaCTICS as well as contouring atlases to allow evaluation of their contours in reference to other users as well as reference ROIs. The residents then contoured a second case using these resources. Volume overlap metrics between the users showed a substantial improvement following the intervention. Additionally, 66% of users reported that they found TaCTICS to be a useful educational tool and all participants reported they would like to use TaCTICS to track their contouring skills over the course of their residency.

  6. Alcohol-impaired driving and its consequences in the United States: the past 25 years.

    Science.gov (United States)

    Williams, Allan F

    2006-01-01

    Progress in dealing with the alcohol-impaired driving problem in the United States during the past 25 years is addressed. Trends in various measures of the problem were tracked and a thorough review of the relevant literature conducted. In the 1980s and continuing into the early 1990s, major decreases occurred in alcohol-impaired driving and its consequences. The contribution of alcohol to fatal crashes dropped by 35-40% during this period. Two primary reasons for the decline appear to be the emergence of citizen activist groups that mobilized public support and attention to the problem, and the proliferation of effective laws. Since about 1995 the alcohol-impaired driving problem has stabilized at a reduced but still quite high level. Highway safety organizations and citizen activist groups have continued to highlight the problem, but its status as a social issue has diminished. We basically know what the primary target groups are, and we know measures that would work to reduce the problem if implemented more fully. We know that political leadership, state task forces, and media advocacy are important ingredients in addressing the problem. It is likely that a resurgence in citizen activism will be necessary to foster these elements and refocus the nation on the unfinished battle against alcohol-impaired driving. Alcohol-impaired driving is still a major problem that needs continuing attention.

  7. Hypertension and cognitive impairment

    Directory of Open Access Journals (Sweden)

    Su-hang SHANG

    2015-08-01

    Full Text Available As a leading risk factor for stroke, hypertension is also an important risk factor for cognitive impairment. Midlife hypertension doubles the risk of dementia later in life and accelerates the progression of dementia, but the correlation between late-life blood pressure and cognitive impairment is still unclear. Beside blood pressure, the effect of pulse pressure, blood pressure variability and circadian rhythm of blood pressure on cognition is currently attracting more and more attention. Hypertension induces alterations in cerebrovascular structure and functions, which lead to brain lesions including cerebral atrophy, stroke, lacunar infarcts, diffuse white matter damage, microinfarct and microhemorrhage, resuling in cognitive impairment. Hypertension also impairs the metabolism and transfer of amyloid-β protein (Aβ, thus accelerates cognitive impairment. Individualized therapy, focusing on characteristics of hypertensive patients, may be a good choice for prevention and treatment of cognitive impairment. DOI: 10.3969/j.issn.1672-6731.2015.08.004

  8. Music Therapy for the Visually Impaired.

    Science.gov (United States)

    Steele, Anita Louise; Crawford, Celeste

    1982-01-01

    The development and implementation of a music therapy program to achieve behavioral change in visually impaired children and adolescents are described. Goals targeted by the music therapist at the Cleveland Society for the Blind include altering unusual body movements, poor posture, and other mannerisms often associated with blindness. (SEW)

  9. Preventing cognitive impairment in children with epilepsy

    NARCIS (Netherlands)

    Braun, Kees P J

    PURPOSE OF REVIEW: Cognitive impairments are common in children with epilepsy. They may already be present before the onset of epilepsy or occur – and even progress – during its course. Many variables contribute to cognitive dysfunction. Those that can be targeted to prevent (further) cognitive

  10. 78 FR 73373 - National Impaired Driving Prevention Month, 2013

    Science.gov (United States)

    2013-12-05

    ... ourselves to saving lives and eliminating drunk, drugged, and distracted driving. Impaired drivers are... tools and training to decrease drunk and drugged driving. We are designing effective, targeted... Impaired Driving Prevention Month, 2013 #0; #0; #0; Presidential Documents #0; #0; #0;#0;Federal Register...

  11. Intercomparison of Dosimeters for Non-Target Organ Dose Measurements in Radiotherapy - Activity of EURADOS WG 9: Radiation Protection in Medicine

    International Nuclear Information System (INIS)

    Miljanic, S.; Knezevic, Z.; Bessieres, I.; Bordy, J.-M.; D'Agostino, E.; d'Errico, F.; di Fulvio, A.; Domingo, C.; Olko, P.; Stolarczyk; Silari, M.; Harrison, R.

    2011-01-01

    It has been known for a long time that patients treated with ionizing radiation carry a risk of developing radiation induced cancer in their lifetimes. It is recognized that cure/survival rates in radiotherapy are increasing, but so are secondary cancers. These occurrences are amplified by the early detection of disease in younger patients. These patients are cured from the primary disease and have long life-expectancies, which increase their chances of developing secondary malignancies. The motivation of the EURADOS Working Group 9 (WG 9) ''Radiation protection dosimetry in medicine'' is to assess undue non-target patient doses in radiotherapy and the related risks of secondary malignancy with the most accredited available methods and with the emphasis on a thorough evaluation of dosimetry methods for the measurements of doses remote from the target volume, in phantom experiments. The development of a unified and comprehensive dosimetry methodology for non-target dose estimation is the key element of the WG9 current work. The first scientific aim is to select and review dosimeters suitable for photon and neutron dosimetry in radiotherapy and to evaluate the characteristics of dosimeters at CEA LIST Saclay in reference clinical LINAC beam. (author)

  12. Children with motor impairment related to cerebral palsy: Prevalence, severity and concurrent impairments in China.

    Science.gov (United States)

    He, Ping; Chen, Gong; Wang, Zhenjie; Guo, Chao; Zheng, Xiaoying

    2017-05-01

    Cerebral palsy (CP) is the most common cause of motor impairment in childhood. This study aimed to examine the prevalence, severity and concurrent impairments of CP-related motor impairment among Chinese children. Children with CP-related motor impairment aged 0-17 years were identified through a national population-based survey based on World Health Organization International Classification of Functioning, Disability and Health. Logistic regression models allowing for weights were used to examine individual and family factors in relation to CP-related motor impairment. The weighted prevalence of CP-related motor impairment was 1.25 per 1000 children (95% confidence interval (CI): 1.16, 1.35) in China. Male children, children in multiples and in families where adults suffered from CP, were more likely to be affected by CP-related motor impairment. For mild, moderate, severe and extremely severe groups of motor impairment, weighted proportions of CP were 14.12% (95%CI: 11.70, 16.95), 20.35% (95%CI: 17.48, 23.56), 27.44% (95%CI: 24.25, 30.87) and 38.09% (95%CI: 34.55, 41.76), respectively; and weighted proportions of concurrent visual, hearing and cognitive impairment were 5.00% (95%CI: 3.59, 6.91), 6.98% (95%CI: 5.34, 9.08) and 71.06% (95%CI: 67.57, 74.31), respectively. Gender, multiple births and family adults with CP were significantly associated with CP-related motor impairment in Chinese children. Proportions of CP and concurrent impairments that increased with severity of motor impairment were observed. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  13. Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome

    NARCIS (Netherlands)

    Damman, Jeffrey; Bloks, Vincent W.; Daha, Mohamed R.; van der Most, Peter J.; Sanjabi, Bahram; van der Vlies, Pieter; Snieder, Harold; Ploeg, Rutger J.; Krikke, Christina; Leuvenink, Henri G. D.; Seelen, Marc A.

    2015-01-01

    Background. In the last few decades, strategies to improve allograft survival after kidney transplantation have been directed to recipient-dependent mechanisms of renal injury. In contrast, no such efforts have been made to optimize organ quality in the donor. Optimizing deceased donor kidney

  14. Criteria for driver impairment

    NARCIS (Netherlands)

    Brookhuis, K.A.; De Waard, D.; Fairclough, S.H

    2003-01-01

    Most traffic accidents can be attributed to driver impairment, e.g. inattention, fatigue, intoxication, etc. It is now technically feasible to monitor and diagnose driver behaviour with respect to impairment with the aid of a limited number of in-vehicle sensors. However, a valid framework for the

  15. Evidence of independent action of neurohypophyseal peptides on osmotic water flow and active sodium transport in the same target organ: studies on RANA esculenta skin and bladder (1961)

    International Nuclear Information System (INIS)

    Bourguet, J.; Maetz, J.

    1961-01-01

    Neurohypophyseal peptides produce on the skin and bladder of certain amphibia simultaneous increases of the passive osmotic permeability to water and active transport of sodium. The present work shows that oxytocin and two of its analogues arginine-8-oxytocin (arginine vasotocin) and lysine-8-oxytocin (lysine vasotocin) may produce the same increase of water permeability, while stimulating in quite different ways the sodium transport. This is the case for both skin and bladder. In other words, there is no correlation between natriferic and hydro-osmotic activities. The results are interpreted as evidence that neurohypophyseal hormones act on not one, as previously assumed, but two targets, inside the same epithelial cell. (author) [fr

  16. Toxicity of anti-fouling paints for use on ships and leisure boats to non-target organisms representing three trophic levels.

    Science.gov (United States)

    Karlsson, Jenny; Ytreberg, Erik; Eklund, Britta

    2010-03-01

    Leachates of anti-fouling paints for use on ships and leisure boats are examined for their ecotoxicological potential. Paint leachates were produced in both 7 per thousand artificial (ASW) and natural seawater (NSW) and tested on three organisms, the bacterium Vibrio fischeri, the macroalga Ceramium tenuicorne, and the crustacean Nitocra spinipes. Generally, leaching in ASW produced a more toxic leachate and was up to 12 times more toxic to the organisms than was the corresponding NSW leachate. The toxicity could be explained by elevated concentrations of Cu and Zn in the ASW leachates. Of the NSW leachates, those from the ship paints were more toxic than those from leisure boat paints. The most toxic paint was the biocide-free leisure boat paint Micron Eco. This implies that substances other than added active agents (biocides) were responsible for the observed toxicity, which would not have been discovered without the use of biological tests. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  17. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner

    NARCIS (Netherlands)

    Gupta, V.K.; Scheunemann, L.; Eisenberg, T.; Mertel, S.; Bhukel, A.; Koemans, T.S.; Kramer, J.M.; Liu, K.S.; Schroeder, S.; Stunnenberg, H.G.; Sinner, F.; Magnes, C.; Pieber, T.R.; Dipt, S.; Fiala, A.; Schenck, A.; Schwaerzel, M.; Madeo, F.; Sigrist, S.J.

    2013-01-01

    Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the

  18. Investigating the organic and conventional production type of olive oil with target and suspect screening by LC-QTOF-MS, a novel semi-quantification method using chemical similarity and advanced chemometrics.

    Science.gov (United States)

    Kalogiouri, Natasa P; Aalizadeh, Reza; Thomaidis, Nikolaos S

    2017-09-01

    The discrimination of organic and conventional production has been a critical topic of public discussion and constitutes a scientific issue. It remains a challenge to establish a correlation between the agronomical practices and their effects on the composition of olive oils, especially the phenolic composition, since it defines their organoleptic and nutritional value. Thus, a liquid chromatography-electrospray ionization-quadrupole time of flight tandem mass spectrometric method was developed, using target and suspect screening workflows, coupled with advanced chemometrics for the identification of phenolic compounds and the discrimination between organic and conventional extra virgin olive oils. The method was optimized by one-factor design and response surface methodology to derive the optimal conditions of extraction (methanol/water (80:20, v/v), pure methanol, or acetonitrile) and to select the most appropriate internal standard (caffeic acid or syringaldehyde). The results revealed that extraction with methanol/water (80:20, v/v) was the optimum solvent system and syringaldehyde 1.30 mg L -1 was the appropriate internal standard. The proposed method demonstrated low limits of detection in the range of 0.002 (luteolin) to 0.028 (tyrosol) mg kg -1 . Then, it was successfully applied in 52 olive oils of Kolovi variety. In total, 13 target and 24 suspect phenolic compounds were identified. Target compounds were quantified with commercially available standards. A novel semi-quantitation strategy, based on chemical similarity, was introduced for the semi-quantification of the identified suspects. Finally, ant colony optimization-random forest model selected luteolin as the only marker responsible for the discrimination, during a 2-year study. Graphical abstract Investigation of the organic and conventional production type of olive oil by LC-QTOF-MS.

  19. SU-F-BRB-13: Correlation of Improved Target and Organ-At-Risk Dosimetric Quantities and Clinical Outcomes for Helical Tomotherapy Treated Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Qi, S; Kishan, A; Alexander, S; Lee, P; Selch, M; Kupelian, P; Steiberg, M; Low, D [UCLA, Los Angeles, CA (United States)

    2015-06-15

    Purpose: We have observed improved local control probability (LCP) for adjuvant mesothelioma radiotherapy following pleurectomy/decortication using Tomotherapy compared to the conventional 3D technique (p<0.05). This work assesses the correlation between the improved clinical outcomes against dosimetry quantities. Methods: Thirty-eight mesothelioma cases consecutively treated at our clinic were retrospectively analyzed. Sixteen patients were treated using 3D technique planned on the Eclipse for c-arm accelerators prior to 7/2012; the other 22 cases were treated on Tomotherapy using helical IMRT after 7/2012. Typical 3D plans consisting of 15 MV AP/PA photon fields prescribed to 10 cm depth followed by matching electron fields with energy ranging from 8–16 MeV. Tomotherapy plans were designed using 2.5cm jaw, 0.287 pitch with directional blocking of the contralateral lung. The same prescription of 45 Gy (1.8GyX25) was used for both techniques. The dosimetry metrics for the critical structures: ipsilateral-/contralateral-lung, heart, cord, esophagus, etc were compared between two techniques. Results: Superior LCP is closely associated with improved target coverage. Tomotherapy plans yielded dramatically better target coverage and less dose heterogeneity despite of more advanced/larger disease. The averaged PTV volumes were 2287.3±569.9 (Tomotherapy) vs. 1904.8±312.3cc (3D); V100s were: 91.1±4.0 (%) vs. 47.8±12.7 (%) with heterogeneity indices of 1.20±0.1 vs.1.37±0.38 and for the Tomotherapy and 3D plans, respectively. Compared to the 3D technique, we observed significant lower maximum cord doses (p<0.001), lower mean esophagus doses (p<0.002), and lower heart mean doses when tumor was left-sided (p=0.002). For ipsilateral-/contralateral-lungs, however, the mean doses and V20, V5 of Tomotherapy plans were significantly higher than the 3D plans (p<0.01) regardless which sides of lung were treated. However, rates of radiation pneumonitis were no different

  20. Congenital hearing impairment

    International Nuclear Information System (INIS)

    Robson, Caroline D.

    2006-01-01

    Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling. High-resolution CT and MRI have contributed to the evaluation and management of hearing impairment. In addition, with the identification of innumerable genetic loci and genetic defects involved in hearing loss, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment. Some of the common forms of congenital hearing loss are reviewed and their imaging features illustrated. (orig.)

  1. Impairment in Non-Word Repetition: A Marker for Language Impairment or Reading Impairment?

    Science.gov (United States)

    Baird, Gillian; Slonims, Vicky; Simonoff, Emily; Dworzynski, Katharina

    2011-01-01

    Aim: A deficit in non-word repetition (NWR), a measure of short-term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language…

  2. Will weight loss cause significant dosimetric changes of target volumes and organs at risk in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy?

    International Nuclear Information System (INIS)

    Chen, Chuanben; Fei, Zhaodong; Chen, Lisha; Bai, Penggang; Lin, Xiang; Pan, Jianji

    2014-01-01

    This study aimed to quantify dosimetric effects of weight loss for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Overall, 25 patients with NPC treated with IMRT were enrolled. We simulated weight loss during IMRT on the computer. Weight loss model was based on the planning computed tomography (CT) images. The original external contour of head and neck was labeled plan 0, and its volume was regarded as pretreatment normal weight. We shrank the external contour with different margins (2, 3, and 5 mm) and generated new external contours of head and neck. The volumes of reconstructed external contours were regarded as weight during radiotherapy. After recontouring outlines, the initial treatment plan was mapped to the redefined CT scans with the same beam configurations, yielding new plans. The computer model represented a theoretical proportional weight loss of 3.4% to 13.7% during the course of IMRT. The dose delivered to the planning target volume (PTV) of primary gross tumor volume and clinical target volume significantly increased by 1.9% to 2.9% and 1.8% to 2.9% because of weight loss, respectively. The dose to the PTV of gross tumor volume of lymph nodes fluctuated from −2.0% to 1.0%. The dose to the brain stem and the spinal cord was increased (p < 0.001), whereas the dose to the parotid gland was decreased (p < 0.001). Weight loss may lead to significant dosimetric change during IMRT. Repeated scanning and replanning for patients with NPC with an obvious weight loss may be necessary

  3. Will weight loss cause significant dosimetric changes of target volumes and organs at risk in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chuanben; Fei, Zhaodong; Chen, Lisha; Bai, Penggang; Lin, Xiang; Pan, Jianji, E-mail: jianjipan@126.com

    2014-04-01

    This study aimed to quantify dosimetric effects of weight loss for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Overall, 25 patients with NPC treated with IMRT were enrolled. We simulated weight loss during IMRT on the computer. Weight loss model was based on the planning computed tomography (CT) images. The original external contour of head and neck was labeled plan 0, and its volume was regarded as pretreatment normal weight. We shrank the external contour with different margins (2, 3, and 5 mm) and generated new external contours of head and neck. The volumes of reconstructed external contours were regarded as weight during radiotherapy. After recontouring outlines, the initial treatment plan was mapped to the redefined CT scans with the same beam configurations, yielding new plans. The computer model represented a theoretical proportional weight loss of 3.4% to 13.7% during the course of IMRT. The dose delivered to the planning target volume (PTV) of primary gross tumor volume and clinical target volume significantly increased by 1.9% to 2.9% and 1.8% to 2.9% because of weight loss, respectively. The dose to the PTV of gross tumor volume of lymph nodes fluctuated from −2.0% to 1.0%. The dose to the brain stem and the spinal cord was increased (p < 0.001), whereas the dose to the parotid gland was decreased (p < 0.001). Weight loss may lead to significant dosimetric change during IMRT. Repeated scanning and replanning for patients with NPC with an obvious weight loss may be necessary.

  4. Toxicity of anti-fouling paints for use on ships and leisure boats to non-target organisms representing three trophic levels

    International Nuclear Information System (INIS)

    Karlsson, Jenny; Ytreberg, Erik; Eklund, Britta

    2010-01-01

    Leachates of anti-fouling paints for use on ships and leisure boats are examined for their ecotoxicological potential. Paint leachates were produced in both 7 per mille artificial (ASW) and natural seawater (NSW) and tested on three organisms, the bacterium Vibrio fischeri, the macroalga Ceramium tenuicorne, and the crustacean Nitocra spinipes. Generally, leaching in ASW produced a more toxic leachate and was up to 12 times more toxic to the organisms than was the corresponding NSW leachate. The toxicity could be explained by elevated concentrations of Cu and Zn in the ASW leachates. Of the NSW leachates, those from the ship paints were more toxic than those from leisure boat paints. The most toxic paint was the biocide-free leisure boat paint Micron Eco. This implies that substances other than added active agents (biocides) were responsible for the observed toxicity, which would not have been discovered without the use of biological tests. - Leachate from a biocide-free anti-fouling paint for leisure boat use was more toxic than leachates from ship paints.

  5. Impairments to Vision

    Science.gov (United States)

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  6. Stormwater Impaired Watersheds

    Data.gov (United States)

    Vermont Center for Geographic Information — Stormwater impaired watersheds occuring on both the Priority Waters (Part D - Completed TMDL) and 303(d) list of waters (Part A - need TMDL) The Vermont State...

  7. Assessment of biological effects of environmental pollution in Mersin Bay (Turkey, northeastern Mediterranean Sea) using Mullus barbatus and Liza ramada as target organisms.

    Science.gov (United States)

    Yılmaz, Doruk; Kalay, Mustafa; Dönmez, Erdem; Yılmaz, Nejat

    2016-01-01

    The increasing emphasis on the assessment and monitoring of marine ecosystems has revealed the need to use appropriate biological indicators for these areas. Enzyme activities and histopathology are increasingly being used as indicators of environmental stress since they provide a definite biological end-point of pollutant exposure. As part of an ecotoxicological assessment of Mersin Bay, EROD enzyme activity and histopathological response in selected organs and tissues of two species of fish, Mullus barbatus (red mullet) and Liza ramada (thinlip grey mullet), captured from area were examined. Pollutant (Organochlorines (OC), alkylphenols (APs) and BPA) levels and biomarker responses in tissue samples were evaluated together for their potential to alter the metabolism and cellular aspects in liver and gonad. Elevated induction of EROD activity and histopathological alterations in contaminated samples from Mersin Bay was observed compared to reference site indicating the exposure to potential pollutants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Organization of Circadian Behavior Relies on Glycinergic Transmission

    Directory of Open Access Journals (Sweden)

    Lia Frenkel

    2017-04-01

    Full Text Available The small ventral lateral neurons (sLNvs constitute a central circadian pacemaker in the Drosophila brain. They organize daily locomotor activity, partly through the release of the neuropeptide pigment-dispersing factor (PDF, coordinating the action of the remaining clusters required for network synchronization. Despite extensive efforts, the basic principles underlying communication among circadian clusters remain obscure. We identified classical neurotransmitters released by sLNvs through disruption of specific transporters. Adult-specific RNAi-mediated downregulation of the glycine transporter or impairment of glycine synthesis in LNv neurons increased period length by nearly an hour without affecting rhythmicity of locomotor activity. Electrophysiological recordings showed that glycine reduces spiking frequency in circadian neurons. Interestingly, downregulation of glycine receptor subunits in specific sLNv targets impaired rhythmicity, revealing involvement of glycine in information processing within the network. These data identify glycinergic inhibition of specific targets as a cue that contributes to the synchronization of the circadian network.

  9. Nighttime Systolic Blood-Pressure Load Is Correlated with Target-Organ Damage Independent of Ambulatory Blood-Pressure Level in Patients with Non-Diabetic Chronic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    Full Text Available The impacts of blood pressure (BP load on target-organ damage in patients with chronic kidney disease (CKD are largely unclear. We examined whether BP load is correlated with target-organ damage (TOD in Chinese CKD patients independent of BP level.We recruited 1219 CKD patients admitted to our hospital division in this cross-sectional study. The TOD were measured by estimated glomerular filtration rate (eGFR, proteinuria, left ventricular mass index (LVMI and carotid intima-media thickness (cIMT in this study. Univariate and multivariate linear analyses were used to evaluate the relationship between systolic blood pressure (SBP load, diastolic blood pressure (DBP load and these renal, cardiovascular parameters.In multivariable-adjusted models, BP load and ambulatory BP levels both independently correlated with LVMI, eGFR and proteinuria in all groups of CKD patients (p0.008, P<0.05 in multivariable-adjusted model which already including the 24-h BP. BP load did not refine this correlation based on the 24-h BP level in diabetic CKD patients.Night-time SBP load was correlated with TOD in patients with non-diabetic chronic kidney disease independent of BP level.

  10. Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders.

    Science.gov (United States)

    Fraldi, Alessandro; Annunziata, Fabio; Lombardi, Alessia; Kaiser, Hermann-Josef; Medina, Diego Luis; Spampanato, Carmine; Fedele, Anthony Olind; Polishchuk, Roman; Sorrentino, Nicolina Cristina; Simons, Kai; Ballabio, Andrea

    2010-11-03

    The function of lysosomes relies on the ability of the lysosomal membrane to fuse with several target membranes in the cell. It is known that in lysosomal storage disorders (LSDs), lysosomal accumulation of several types of substrates is associated with lysosomal dysfunction and impairment of endocytic membrane traffic. By analysing cells from two severe neurodegenerative LSDs, we observed that cholesterol abnormally accumulates in the endolysosomal membrane of LSD cells, thereby reducing the ability of lysosomes to efficiently fuse with endocytic and autophagic vesicles. Furthermore, we discovered that soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs), which are key components of the cellular membrane fusion machinery are aberrantly sequestered in cholesterol-enriched regions of LSD endolysosomal membranes. This abnormal spatial organization locks SNAREs in complexes and impairs their sorting and recycling. Importantly, reducing membrane cholesterol levels in LSD cells restores normal SNARE function and efficient lysosomal fusion. Our results support a model by which cholesterol abnormalities determine lysosomal dysfunction and endocytic traffic jam in LSDs by impairing the membrane fusion machinery, thus suggesting new therapeutic targets for the treatment of these disorders.

  11. Bibliometric analysis of papers on mild cognitive impairment nursing in China

    Directory of Open Access Journals (Sweden)

    Yating Ai

    2017-01-01

    Conclusion: Beijing and Shanghai established core author groups for mild cognitive impairment nursing research. These studies should focus on the community and psychological nursing of such impairment. Targeted nursing interventions on different types of mild cognitive impairment should be adopted, new avenues for research should be opened, and various research methods should be introduced.

  12. Sexual Behavior Among Persons With Cognitive Impairments.

    Science.gov (United States)

    Thom, Robyn P; Grudzinskas, Albert J; Saleh, Fabian M

    2017-05-01

    Although the cognitively impaired are frequently included in heterogeneous studies of problematic sexual behavior, the epidemiology, etiology, and approach to assessment and treatment of persons with dementia and intellectual disability are distinct from those of the general population. The incidence of inappropriate sexual behavior among the intellectually disabled is 15-33%; however, the nature tends to be more socially inappropriate than with violative intent. Limited sociosexual education is a large contributor, and better addressing this area offers a target for prevention and treatment. A thorough clinical assessment of problematic sexual behaviors in the cognitively impaired requires understanding the patient's internal experience, which can be challenging. Assessment tools validated for the general population have not been validated for this population. Very few studies have assessed treatment approaches specifically among the cognitively impaired; however, research does suggest utility in habilitative, psychotherapeutic, and pharmacologic approaches which have been validated among the general population.

  13. Evaluating the efficiency of advanced wastewater treatment: target analysis of organic contaminants and (geno-)toxicity assessment tell a different story.

    Science.gov (United States)

    Magdeburg, Axel; Stalter, Daniel; Schlüsener, Michael; Ternes, Thomas; Oehlmann, Jörg

    2014-03-01

    At a pilot scale wastewater treatment plant ozonation and powdered activated carbon filtration were assessed for their efficacy to remove trace organic contaminants from secondary treated effluents. A chemical analysis of 16 organic compounds was accompanied by a comprehensive suite of in vitro and in vivo bioassays with the focus on genotoxicity to account for the potential formation of reactive oxidation products. In vitro experiments were performed with solid phase extracted water samples, in vivo experiments with native wastewater in a flow through test system on site at the treatment plant. The chemical evaluation revealed an efficient oxidation of about half of the selected compounds by more than 90% at an ozone dose of 0.7 g/g DOC. A lower oxidizing efficiency was observed for the iodinated X-ray contrast media (49-55%). Activated carbon treatment (20 mg/L) was less effective for the removal of most pharmaceuticals monitored. The umuC assay on genotoxicity delivered results with about 90% decrease of the effects by ozonation and slightly lower efficiency for PAC treatment. However, the Ames test on mutagenicity with the strain YG7108 revealed a consistent and ozone-dose dependent increase of mutagenicity after wastewater ozonation compared to secondary treatment. Sand filtration as post treatment step reduced the ozone induced mutagenicity only partly. Also the fish early life stage toxicity test revealed an increase in mortality after ozonation and a reduced effect after sand filtration. Only activated carbon treatment reduced the fish mortality compared to conventional treatment on control level. Likewise the in vivo genotoxicity detected with the comet assay using fish erythrocytes confirmed an increased (geno-)toxicity after ozonation, an effect decrease after sand-filtration and no toxic effects after activated carbon treatment. This study demonstrates the need for a cautious selection of methods for the evaluation of advanced (oxidative

  14. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  15. Type 2 diabetes mellitus and exercise impairment.

    Science.gov (United States)

    Reusch, Jane E B; Bridenstine, Mark; Regensteiner, Judith G

    2013-03-01

    Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.

  16. Comparison of radiation absorbed dose in target organs in maxillofacial imaging with panoramic, conventional linear tomography, cone beam computed tomography and computed tomography

    Directory of Open Access Journals (Sweden)

    Panjnoush M.

    2009-12-01

    Full Text Available "nBackground and Aim: The objective of this study was to measure and compare the tissue absorbed dose in thyroid gland, salivary glands, eye and skin in maxillofacial imaging with panoramic, conventional linear tomography, cone beam computed tomography (CBCT and computed tomography (CT."nMaterials and Methods: Thermoluminescent dosimeters (TLD were implanted in 14 sites of RANDO phantom to measure average tissue absorbed dose in thyroid gland, parotid glands, submandibular glands, sublingual gland, lenses and buccal skin. The Promax (PLANMECA, Helsinki, Finland unit was selected for Panoramic, conventional linear tomography and cone beam computed tomography examinations and spiral Hispeed/Fxi (General Electric,USA was selected for CT examination. The average tissue absorbed doses were used for the calculation of the equivalent and effective doses in each organ."nResults: The average absorbed dose for Panoramic ranged from 0.038 mGY (Buccal skin to 0.308 mGY (submandibular gland, linear tomography ranged from 0.048 mGY (Lens to 0.510 mGY (submandibular gland,CBCT ranged from 0.322 mGY (thyroid glad to 1.144 mGY (Parotid gland and in CT ranged from 2.495 mGY (sublingual gland to 3.424 mGY (submandibular gland. Total effective dose in CBCT is 5 times greater than Panoramic and 4 times greater than linear tomography, and in CT, 30 and 22 times greater than Panoramic and linear tomography, respectively. Total effective dose in CT is 6 times greater than CBCT."nConclusion: For obtaining 3-dimensional (3D information in maxillofacial region, CBCT delivers the lower dose than CT, and should be preferred over a medical CT imaging. Furthermore, during maxillofacial imaging, salivary glands receive the highest dose of radiation.

  17. Trainable Mentally Impaired/Severely Multiply Impaired/Autistic Impaired/Severely Mentally Impaired. Product Evaluation Report 1989-1990.

    Science.gov (United States)

    Claus, Richard N.; And Others

    The evaluation report describes special education services provided to trainable mentally impaired (TMI), autistic impaired (AI), severely multiply impaired (SXI), and severely mentally impaired (SMI) students at and through the Melvin G. Millet Learning Center (Bridgeport, Michigan). The eight program components are described individually and…

  18. Central blood pressure and pulse wave velocity: relationship to target organ damage and cardiovascular morbidity-mortality in diabetic patients or metabolic syndrome. An observational prospective study. LOD-DIABETES study protocol.

    Science.gov (United States)

    Gómez-Marcos, Manuel A; Recio-Rodríguez, José I; Rodríguez-Sánchez, Emiliano; Castaño-Sánchez, Yolanda; de Cabo-Laso, Angela; Sánchez-Salgado, Benigna; Rodríguez-Martín, Carmela; Castaño-Sánchez, Carmen; Gómez-Sánchez, Leticia; García-Ortiz, Luis

    2010-03-18

    Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes (cardiovascular mortality, myocardial infarction, chest pain and stroke) in patients with type 2 diabetes mellitus or metabolic syndrome. This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up. The study will be carried out in the urban primary care setting. Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included. Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together

  19. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  20. Social communication impairments: pragmatics.

    Science.gov (United States)

    Russell, Robert L

    2007-06-01

    Social communication or pragmatic impairments are characterized and illustrated as involving inappropriate or ineffective use of language and gesture in social contexts. Three clinical vignettes illustrate different pragmatic impairments and the wealth of diagnostic information that can be garnered from observation of a child's social communication behavior. Definitions of, and developmental milestones in, domains of pragmatic competence are provided. Several screening instruments are suggested for use in assessing pragmatic competence within the time-frame of a pediatric examination. Frequent comorbid psychiatric conditions are described and a sample of current neurobiologic research is briefly summarized.

  1. Cognitive impairment in Wilson's disease

    Directory of Open Access Journals (Sweden)

    Norberto Anizio Ferreira Frota

    Full Text Available Abstract Wilson's disease (WD or hepatolenticular degeneration is a rare, genetic and systemic disease, caused by a deficit in the metabolism of copper, leading to its accumulation in different organs, mainly the liver, followed by the central nervous system, especially the basal ganglia. When symptoms begin between the second and third decades of life, approximately 50% of the patients show neurological symptoms. Although dystonia and dysarthria are the most common neurological signs, cognitive changes have been reported since the first cases were described in 1912. Memory change is one of the most common impairments, but other cognitive changes have been reported, including dementia in untreated cases. In this article we review the cognitive changes in WD patients and the occurrence of dementia.

  2. Medications and impaired driving.

    Science.gov (United States)

    Hetland, Amanda; Carr, David B

    2014-04-01

    To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on classes of medications associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Only English-language articles that contained findings from observational or interventional designs with ≥ 10 participants were included in this review. Cross-sectional studies, case series, and case reports were excluded. Driving is an important task and activity for the majority of adults. Some commonly prescribed medications have been associated with driving impairment measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, hypnotics, antidepressants, opioid and nonsteroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies of medication impact on sedation, sleep latency, and psychomotor function, as well as the role of alcohol, are also discussed. Psychotropic agents and those with central nervous system side effects were associated with measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific classes of medications, educate their patients, and/or consider safer alternatives.

  3. Organics Verification Study for Sinclair and Dyes Inlets, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, Nancy P.; Brandenberger, Jill M.; Niewolny, Laurie A.; Johnston, Robert K.

    2006-09-28

    Sinclair and Dyes Inlets near Bremerton, Washington, are on the State of Washington 1998 303(d) list of impaired waters because of fecal coliform contamination in marine water, metals in sediment and fish tissue, and organics in sediment and fish tissue. Because significant cleanup and source control activities have been conducted in the inlets since the data supporting the 1998 303(d) listings were collected, two verification studies were performed to address the 303(d) segments that were listed for metal and organic contaminants in marine sediment. The Metals Verification Study (MVS) was conducted in 2003; the final report, Metals Verification Study for Sinclair and Dyes Inlets, Washington, was published in March 2004 (Kohn et al. 2004). This report describes the Organics Verification Study that was conducted in 2005. The study approach was similar to the MVS in that many surface sediment samples were screened for the major classes of organic contaminants, and then the screening results and other available data were used to select a subset of samples for quantitative chemical analysis. Because the MVS was designed to obtain representative data on concentrations of contaminants in surface sediment throughout Sinclair Inlet, Dyes Inlet, Port Orchard Passage, and Rich Passage, aliquots of the 160 MVS sediment samples were used in the analysis for the Organics Verification Study. However, unlike metals screening methods, organics screening methods are not specific to individual organic compounds, and are not available for some target organics. Therefore, only the quantitative analytical results were used in the organics verification evaluation. The results of the Organics Verification Study showed that sediment quality outside of Sinclair Inlet is unlikely to be impaired because of organic contaminants. Similar to the results for metals, in Sinclair Inlet, the distribution of residual organic contaminants is generally limited to nearshore areas already within the

  4. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  5. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    2010-01-01

    BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS...

  6. Piracetam treatment in patients with cognitive impairment.

    Science.gov (United States)

    Rao, Mukund G; Holla, Bharath; Varambally, Shivarama; Raveendranathan, Dhanya; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2013-01-01

    Piracetam is a cognitive-enhancing agent that is used for the treatment of cognitive impairments of various etiologies. Little is known about its side effect profile, especially in those with psychiatric illness. We herewith present two cases with cognitive impairment who had contrasting responses to piracetam. One of them with organic amnestic syndrome had significant improvement, whereas the other who had an organic personality change as well as a family history of mental illness had significant worsening of behavioral problems after piracetam was introduced. This report highlights the need for caution in the use of piracetam, especially in those with past or family history of psychiatric illness. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. iShoes for blind and visually impaired people

    OpenAIRE

    Assairi, Bandar; Holmes, Violeta

    2013-01-01

    This paper presents the development of an iShoes system for blind and visually impaired people. The iShoes system utilizes a microcontroller with sound output interfaced with ultrasonic sensors. The prototype system is designed to be specifically mounted on/in the shoes to aid navigation in urban routes. The ultrasonic transducers determine the range from an obstacle and then play an audio message to reflect the distance from the target. This system will assist blind and visually impaired peo...

  8. Counter-Leadership Targeting and Conflict Termination

    National Research Council Canada - National Science Library

    Taylor, Bradly

    1999-01-01

    .... Can the leader be found? And, is it legal and ethical to attack the leader? Analysis rarely has been conducted to determine whether the targeted organization is vulnerable to Counter Leadership Targeting (CLT...

  9. When treating prostate cancer with three-dimensional conformal radiation therapy the impact of bladder filling status on the volume and integral dose distribution of the target and critical organs should be kept in mind

    International Nuclear Information System (INIS)

    Liu Yueping; Liu Xinfan; Li Yexiong; Guang Ying

    2007-01-01

    Objective: In prostate cancer treated with three-dimensional conformal radiation therapy (3DCRT), we tried to prospectively assess the impact of the filling status of bladder on the volume and the integral dose distribution to the target and surrounding critical organs. Methods: Ten patients with stage T1-T2N0M0 prostate cancer were studied. All patients received 3DCRT to the prostate and inferior seminal vesicle. One hour before CT simulation, the bladder was first voided, and then 400 ml of oral contrast solution was given at every half hour before the CT scan. Urethral catheterization was used for voiding or distending the bladder. When distending the bladder, 250-300 ml of contrast was injected into the bladder with the patient fixed at the supine position. Two sets of transverse images were taken for the whole pelvis in empty and full bladder. After the target and critical organs (bladder, rectum, pelvic small bowel, and femoral heads) were contoured, a treatment plan of three-dimensional conformal radiotherapy was made using the CMS Focus-Xio treatment planning system. The volume and mean doses of CTV, PTV, rectum, bladder, femoral heads, and small bowel with the bladder empty and full were evaluated. The percentage of volume which received 50 Gy in the rectum and bladder, 30 Gy in the femoral heads, and the maximal dose to the pelvic small bowel were also assessed . The variability of volume and dose distribution in these targets or organs was compared between the empty and full bladder status. Results: Comparing to the bladder empty status, full bladder led to a mean increase of 499% in the bladder volume, (67±9) ml and (336±48) ml (P=0.000), respectively. No volume change was found in the CTV, PTV, rectum, femoral heads and pel- vic small bowel(P=0.153,0.501,0.929,0.771,0.081). The mean dose to the bladder in full status was only 35% of that in empty status, (1501±201 ) cGy and (4267±216) cGy(P =0.000), respectively. The mean dose to the pelvic small

  10. [Organ failure during the perioperative period: pathophysiology and strategy].

    Science.gov (United States)

    Murakami, M; Murai, N; Kusano, M

    1998-08-01

    After the establishment of the theoretical and clinical background of SIRS, the mechanism of organ failure induction during the perioperative period was gradually clarified. The deterioration of the mutual regulation of cytokines after surgical stress is considered to be a major cause of organ failure. Hypercytokinemia is one of the pathophysiological features after surgical stress, and thus a new therapeutic approach ameliorating the impaired cytokine network has been applied instead of direct targeting therapy for impaired organs. Organ failure can be anticipated based on a precise assessment of the severity of SIRS or CARS. For example, to prevent postsurgical hepatic failure it is important to minimize surgical stress by assessing the preoperative liver reserve capacity. Excessive surgical stress coupled with underestimation of liver function may result in primary multiple organ failure (MOF) after hepatic surgery. Secondary MOF after postsurgical infection may implicate the bacterial translocation mechanism. At present, only CHDF is considered to be a promising therapy for hypercytokinemia. Therefore the prophylactic approach cannot be neglected. The monitoring of cytokines such as IL-6 during the perioperative period provides valuable information for the prediction of organ failure.

  11. Obesity and target organ damage: the kidney

    NARCIS (Netherlands)

    de Jong, P. E.; Verhave, J. C.; Pinto-Sietsma, S. J.; Hillege, H. L.

    2002-01-01

    Obesity is a risk marker for progressive renal function loss in patients with known renal disease. There is, however, increasing evidence that obesity may also damage the kidney in otherwise healthy subjects. There appears to be an intriguing parallel between the renal effects of obesity and those

  12. Obesity and target organ damage : the kidney

    NARCIS (Netherlands)

    de Jong, PE; Verhave, JC; Pinto-Sietsma, SJ; Hillege, HL

    2002-01-01

    Obesity is a risk marker for progressive renal function loss in patients with known renal disease. There is, however, increasing evidence that obesity may also damage the kidney in otherwise healthy subjects. There appears to be an intriguing parallel between the renal effects of obesity and those

  13. Target organ of hCG

    International Nuclear Information System (INIS)

    Yanaginuma, Tsutomu; Kobayashi, Takuro

    1974-01-01

    The author and his associated gave intravenous infusions of hCG labeled with 125 I to female rats and investigated its distribution in their brains. The results showed a significantly higher radioactivity in the median eminence than in the other parts of the brain. This indicated that there were receptors of hCG in the median eminence of the hypothalamus of a female rat. The mechanism of gonadotropin action was also discussed in this report. By giving 125 I and 125 I-BSA to the same rats which had been used in the study of hCG distribution in the brain, and by investigating the radioactivity of their ovaries, the author explained the receptor of gonadotropin in corpora lutea. (Serizawa, K.)

  14. Impaired Consciousness in Epilepsy

    Science.gov (United States)

    Blumenfeld, Hal

    2013-01-01

    Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost making it impossible for the individual to experience or respond. This has huge consequences for safety, productivity, emotional health and quality of life. To prevent impaired consciousness in epilepsy it is necessary to understand the mechanisms leading to brain dysfunction during seizures. Normally the “consciousness system”—a specialized set of cortical-subcortical structures—maintains alertness, attention and awareness. Recent advances in neuroimaging, electrophysiology and prospective behavioral testing have shed new light on how epileptic seizures disrupt the consciousness system. Diverse seizure types including absence, generalized tonic-clonic and complex partial seizures converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding these mechanisms may lead to improved treatment strategies to prevent impaired consciousness and improve quality of life in people with epilepsy. PMID:22898735

  15. Age-Related Sensory Impairments and Risk of Cognitive Impairment

    Science.gov (United States)

    Fischer, Mary E; Cruickshanks, Karen J.; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Tweed, Ted S.

    2016-01-01

    Background/Objectives To evaluate the associations of sensory impairments with the 10-year risk of cognitive impairment. Previous work has primarily focused on the relationship between a single sensory system and cognition. Design The Epidemiology of Hearing Loss Study (EHLS) is a longitudinal, population-based study of aging in the Beaver Dam, WI community. Baseline examinations were conducted in 1993 and follow-up exams have been conducted every 5 years. Setting General community Participants EHLS members without cognitive impairment at EHLS-2 (1998–2000). There were 1,884 participants (mean age = 66.7 years) with complete EHLS-2 sensory data and follow-up information. Measurements Cognitive impairment was a Mini-Mental State Examination score of impairment was a pure-tone average of hearing thresholds (0.5, 1, 2 and 4 kHz) of > 25 decibel Hearing Level in either ear. Visual impairment was Pelli-Robson contrast sensitivity of impairment was a San Diego Odor Identification Test score of impairment were independently associated with cognitive impairment risk [Hearing: Hazard Ratio (HR) = 1.90, 95% Confidence Interval (C.I.) = 1.11, 3.26; Vision: HR = 2.05, 95% C.I. = 1.24, 3.38; Olfaction: HR = 3.92, 95% C.I. = 2.45, 6.26]. However, 85% with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. Conclusion The relationship between sensory impairment and cognitive impairment was not unique to one sensory system suggesting sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. PMID:27611845

  16. Age-Related Sensory Impairments and Risk of Cognitive Impairment.

    Science.gov (United States)

    Fischer, Mary E; Cruickshanks, Karen J; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara E K; Klein, Ronald; Tweed, Ted S

    2016-10-01

    To evaluate the associations between sensory impairments and 10-year risk of cognitive impairment. The Epidemiology of Hearing Loss Study (EHLS), a longitudinal, population-based study of aging in the Beaver Dam, Wisconsin community. Baseline examinations were conducted in 1993 and follow-up examinations have been conducted every 5 years. General community. EHLS members without cognitive impairment at EHLS-2 (1998-2000). There were 1,884 participants (mean age 66.7) with complete EHLS-2 sensory data and follow-up information. Cognitive impairment was defined as a Mini-Mental State Examination score of dementia or Alzheimer's disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5, 1, 2, 4 kHz) of >25 dB hearing level in either ear, visual impairment was a Pelli-Robson contrast sensitivity of impairment was a San Diego Odor Identification Test score of impairment were independently associated with cognitive impairment risk (hearing: hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.11-3.26; vision: HR = 2.05, 95% CI = 1.24-3.38; olfaction: HR = 3.92, 95% CI = 2.45-6.26)). Nevertheless, 85% of participants with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. The relationship between sensory impairment and cognitive impairment was not unique to one sensory system, suggesting that sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  17. The protective properties of Act-Belong-Commit indicators against incident depression, anxiety, and cognitive impairment among older Irish adults

    DEFF Research Database (Denmark)

    Santini, Ziggi Ivan; Koyanagi, Ai; Tyrovolas, Stefanos

    2017-01-01

    The Act-Belong-Commit campaign is the world's first comprehensive, population-wide, community-based program designed to promote mental health. The campaign targets individuals to engage in mentally healthy activities, while at the same time, encouraging community organizations that offer...... the protective effect against cognitive impairment was only marginally significant. Act-Belong-Commit indicators are shown to be protective against mental disorders and cognitive impairment among older Irish adults. This provides further evidence for the campaign's potential efficacy and has potentially wide...... integration (Belong); that is, being well integrated into social networks was a significant protective factor against all mental health outcomes. Finally, frequency of participation in social/recreational activities (Commit) significantly and inversely predicted the onset of depression and anxiety, while...

  18. Impaired decisional impulsivity in pathological videogamers.

    Directory of Open Access Journals (Sweden)

    Michael A Irvine

    Full Text Available Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort.Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice, and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task. We used stringent diagnostic criteria highlighting functional impairment.In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time.We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management.

  19. Voice impairment and menopause.

    Science.gov (United States)

    Schneider, Berit; van Trotsenburg, Michael; Hanke, Gunda; Bigenzahn, Wolfgang; Huber, Johannes

    2004-01-01

    Menopause rating scales still do not regard voice impairment as a genuine climacteric symptom, although voice changes are frequently reported. The purpose of this study was both to register and differentiate voice alterations and disorders in menopausal women. A total of 107 women between 37 and 71 years of age who were rated as postmenopausal according to their hormonal status answered a questionnaire on voice changes and vocal discomfort. Of this group, 49 women mentioned voices changes, and 35 of those women associated these changes with subjective discomfort, whereas 58 women mentioned neither voice changes nor discomfort. Sixteen of the women who mentioned voice changes and eight who did not participated in a comprehensive investigation, which included completion of the Klimax questionnaire, a head and neck examination, videostroboscopy, perceptual evaluation of voice sound, voice range profile measurements, and voice dysfunction index determination. Voice changes during menopause might be a common problem seen in clinical practice. Therefore, an additional systematic registration of voice impairment in future menopause rating scales should be considered if further studies confirm our findings of a high prevalence of voice complaints associated with menopause. Severe menopausal voice impairments, even without other climacteric symptoms, should be regarded as an indication for phoniatric examination.

  20. Influence of visual impairment and hearing impairment on functional dependence status among people in Taiwan—An evaluation using the WHODAS 2.0 score

    Directory of Open Access Journals (Sweden)

    Ko-Fang Chang

    2018-04-01

    Full Text Available Background: Visual impairment (VI and hearing impairment (HI are the two most common types of sensory disability encountered clinically. However, VI and HI result in different limitations in daily life. We assessed the level of functioning in patients with VI or HI based on the International Classification of Functioning, Disability, and Health. Methods: This nationwide, cross-sectional study included 312 people with VI and 540 people with HI. Each participant's degree of functioning and disability was evaluated using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0. The standardized WHODAS 2.0 scores ranged from 0 (least difficulty to 100 (most difficulty. Results: Patients with VI and those with HI had a mean (±standard error 32-item WHODAS 2.0 score of 42.4 ± 2.9 and 27.1 ± 1.6, respectively. The degree of restriction was positively related to the level of VI. Specifically, the patients with VI and a WHODAS 2.0 score of 33.7–35.3 or higher were likely to experience barriers to accessing mobility products, communication products, and education products. Furthermore, patients with a score of 42.9 or higher might experience barriers to accessing ingestion products and living products. Conclusion: WHODAS 2.0 scores are strongly correlated with the severity of VI. Mild VI should be targeted for treatment and referral as early as possible. Compared with the patients with HI, the patients with VI more frequently experience barriers to accessing environmental factors. Keywords: Disability, Functioning, Hearing impairment, International Classification of Functioning (ICF, Visual impairment, WHODAS 2.0

  1. The role of executive functions in social impairment in Autism Spectrum Disorder.

    Science.gov (United States)

    Leung, Rachel C; Vogan, Vanessa M; Powell, Tamara L; Anagnostou, Evdokia; Taylor, Margot J

    2016-01-01

    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by socio-communicative impairments. Executive dysfunction may explain some key characteristics of ASD, both social and nonsocial hallmarks. Limited research exists exploring the relations between executive function and social impairment in ASD and few studies have used a comparison control group. Thus, the objective of the present study was to investigate the relations between executive functioning using the Behavioral Rating Inventory of Executive Functioning (BRIEF), social impairment as measured by the Social Responsiveness Scale (SRS), and overall autistic symptomology as measured by the Autism Diagnostic Observation Schedule (ADOS) in children and adolescents with and without ASD. Seventy children and adolescents diagnosed with ASD and 71 typically developing controls were included in this study. Findings showed that behavioral regulation executive processes (i.e., inhibition, shifting, and emotional control) predicted social function in all children. However, metacognitive executive processes (i.e., initiation, working memory, planning, organization, and monitoring) predicted social function only in children with ASD and not in typically developing children. Our findings suggest a distinct metacognitive executive function-social symptom link in ASD that is not present in the typical population. Understanding components of executive functioning that contribute to the autistic symptomology, particularly in the socio-communicative domain, is crucial for developing effective interventions that target key executive processes as well as underlying behavioral symptoms.

  2. Impairment of insulin signalling in peripheral tissue fails to extend murine lifespan.

    Science.gov (United States)

    Merry, Troy L; Kuhlow, Doreen; Laube, Beate; Pöhlmann, Doris; Pfeiffer, Andreas F H; Kahn, C Ronald; Ristow, Michael; Zarse, Kim

    2017-08-01

    Impaired insulin/IGF1 signalling has been shown to extend lifespan in model organisms ranging from yeast to mammals. Here we sought to determine the effect of targeted disruption of the insulin receptor (IR) in non-neuronal tissues of adult mice on the lifespan. We induced hemizygous (PerIRKO +/- ) or homozygous (PerIRKO -/- ) disruption of the IR in peripheral tissue of 15-weeks-old mice using a tamoxifen-inducible Cre transgenic mouse with only peripheral tissue expression, and subsequently monitored glucose metabolism, insulin signalling and spontaneous death rates over 4 years. Complete peripheral IR disruption resulted in a diabetic phenotype with increased blood glucose and plasma insulin levels in young mice. Although blood glucose levels returned to normal, and fat mass was reduced in aged PerIRKO -/- mice, their lifespan was reduced. By contrast, heterozygous disruption had no effect on lifespan. This was despite young male PerIRKO +/- mice showing reduced fat mass and mild increase in hepatic insulin sensitivity. In conflict with findings in metazoans like Caenorhabditis elegans and Drosophila melanogaster, our results suggest that heterozygous impairment of the insulin signalling limited to peripheral tissues of adult mice fails to extend lifespan despite increased systemic insulin sensitivity, while homozygous impairment shortens lifespan. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. A novel paradigm links mitochondrial dysfunction with muscle stem cell impairment in sepsis.

    Science.gov (United States)

    Chatre, Laurent; Verdonk, Franck; Rocheteau, Pierre; Crochemore, Clément; Chrétien, Fabrice; Ricchetti, Miria

    2017-10-01

    Sepsis is an acute systemic inflammatory response of the body to microbial infection and a life threatening condition associated with multiple organ failure. Survivors may display long-term disability with muscle weakness that remains poorly understood. Recent data suggest that long-term myopathy in sepsis survivors is due to failure of skeletal muscle stem cells (satellite cells) to regenerate the muscle. Satellite cells impairment in the acute phase of sepsis is linked to unusual mitochondrial dysfunctions, characterized by a dramatic reduction of the mitochondrial mass and hyperactivity of residual organelles. Survivors maintain the impairment of satellite cells, including alterations of the mitochondrial DNA (mtDNA), in the long-term. This condition can be rescued by treatment with mesenchymal stem cells (MSCs) that restore mtDNA alterations and mitochondrial function in satellite cells, and in fine their regenerative potential. Injection of MSCs in turn increases the force of isolated muscle fibers and of the whole animal, and improves the survival rate. These effects occur in the context of reduced inflammation markers that also raised during sepsis. Targeting muscle stem cells mitochondria, in a context of reduced inflammation, may represent a valuable strategy to reduce morbidity and long-term impairment of the muscle upon sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Peripheral and central arterial pressure and its relationship to vascular target organ damage in carotid artery, retina and arterial stiffness. Development and validation of a tool. The Vaso risk study

    Directory of Open Access Journals (Sweden)

    Patino-Alonso Maria C

    2011-04-01

    Full Text Available Abstract Background Ambulatory blood pressure monitoring (ABPM shows a better correlation to target organ damage and cardiovascular morbidity-mortality than office blood pressure. A loss of arterial elasticity and an increase in carotid artery intima-media thickness (IMT has been associated with increased cardiovascular morbidity-mortality. Tools have been developed that allow estimation of the retinal arteriovenous index but not all studies coincide and there are contradictory results in relation to the evolution of the arteriosclerotic lesions and the caliber of the retinal vessels. The purpose of this study is to analyze the relationship between peripheral and central arterial pressure (clinic and ambulatory and vascular structure and function as evaluated by the carotid artery intima-media thickness, retina arteriovenous index, pulse wave velocity (PWV and ankle-brachial index in patients with and without type 2 diabetes. In turn, software is developed and validated for measuring retinal vessel thickness and automatically estimating the arteriovenous index. Methods/Design A cross-sectional study involving a control group will be made, with a posterior 4-year follow-up period in primary care. The study patients will be type 2 diabetics, with a control group of non-diabetic individuals. Consecutive sampling will be used to include 300 patients between 34-75 years of age and no previous cardiovascular disease, one-half being assigned to each group. Main measurements: age, gender, height, weight and abdominal circumference. Lipids, creatinine, microalbuminuria, blood glucose, HbA1c, blood insulin, high sensitivity C-reactive protein and endothelial dysfunction markers. Clinic and ambulatory blood pressure monitoring. Carotid ultrasound to evaluate IMT, and retinography to evaluate the arteriovenous index. ECG to assess left ventricle hypertrophy, ankle-brachial index, and pulse wave analysis (PWA and pulse wave velocity (PWV with the Sphigmocor

  5. Accelerator target

    Science.gov (United States)

    Schlyer, David J.; Ferrieri, Richard A.; Koehler, Conrad

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  6. Cognitive impairment and pragmatics.

    Science.gov (United States)

    Gutiérrez-Rexach, Javier; Schatz, Sara

    2016-01-01

    One of the most important ingredients of felicitous conversation exchanges is the adequate expression of illocutionary force and the achievement of perlocutionary effects, which can be considered essential to the functioning of pragmatic competence. The breakdown of illocutionary and perlocutionary functions is one of the most prominent external features of cognitive impairment in Alzheimer's Disease, with devastating psychological and social consequences for patients, their family and caregivers. The study of pragmatic functions is essential for a proper understanding of the linguistic and communicative aspects of Alzheimer's disease.

  7. Memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats.

    Science.gov (United States)

    Godinho, Antonio Francisco; de Oliveira Souza, Ana Carolina; Carvalho, Caio Cristóvão; Horta, Daniel França; De Fraia, Daniel; Anselmo, Fabio; Chaguri, João Leandro; Faria, Caique Aparecido

    2016-10-15

    Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Pavlović Dragan M.

    2009-01-01

    Full Text Available Mild cognitive impairment (MCI is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimer's disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.

  9. Fertility impairment in radiotherapy

    Directory of Open Access Journals (Sweden)

    Marta Biedka

    2016-02-01

    Full Text Available Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient’s sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning.

  10. Vision In Stroke cohort: Profile overview of visual impairment.

    Science.gov (United States)

    Rowe, Fiona J

    2017-11-01

    To profile the full range of visual disorders from a large prospective observation study of stroke survivors referred by stroke multidisciplinary teams to orthoptic services with suspected visual problems. Multicenter prospective study undertaken in 20 acute Trust hospitals. Standardized screening/referral forms and investigation forms documented data on referral signs and symptoms plus type and extent of visual impairment. Of 1,345 patients referred with suspected visual impairment, 915 were recruited (59% men; mean age at stroke onset 69 years [SD 14]). Initial visual assessment was at median 22 days post stroke onset. Eight percent had normal visual assessment. Of 92% with confirmed visual impairment, 24% had reduced central visual acuity visual field loss was present in 52%, most commonly homonymous hemianopia. Fifteen percent had visual inattention and 4.6% had other visual perceptual disorders. Overall 84% were visually symptomatic with visual field loss the most common complaint followed by blurred vision, reading difficulty, and diplopia. Treatment options were provided to all with confirmed visual impairment. Targeted advice was most commonly provided along with refraction, prisms, and occlusion. There are a wide range of visual disorders that occur following stroke and, frequently, with visual symptoms. There are equally a wide variety of treatment options available for these individuals. All stroke survivors require screening for visual impairment and warrant referral for specialist assessment and targeted treatment specific to the type of visual impairment.

  11. [Ophthalmological rehabilitation of visually impaired children].

    Science.gov (United States)

    Altpeter, E K; Nguyen, N X

    2017-07-01

    There are very few studies on visually impaired children in Germany; therefore, the aim of this study was to investigate the current spectrum of diseases of visually impaired children and the care of these children in schools and kindergartens with aids and integrative support. In a retrospective study all children (n =303) who attended the outpatient department for the visually impaired of the University Eye Hospital Tübingen in 2013 and 2014 were evaluated. The target values were ophthalmological diagnosis, best corrected visual acuity, needs for magnification, prescribed aids, measures for early support and integrative care and inclusion during schooltime. The most frequent diagnosis in this collective which led to visual impairment in children was optic atrophy (22.4%) followed by hereditary retinal dystrophy (18.5%), congenital nystagmus (9.9%), albinism (8.6%), retinopathy of prematurity (ROP, 7.9%), aniridia (4.6%), cerebral visual impairment (CVI, 4.3%) and severe myopia (3%). Of the children 21% suffered from multiple disabilities, 66% were visually impaired (visual acuity ≤0.3 and >0.05), 9% were severely visually impaired (visual acuity ≤0.05) and 6% were legally defined as blind (visual acuity ≤0.02). Of the schoolchildren 52% (n = 241) were able to visit a mainstream school within the framework of integrative care. For 77% of these schoolchildren integrative care was already provided by a special pedagogic institution at the time of presentation for school entry and 73% of all the schoolchildren needed magnifying aids at school: 20% used optical magnifying aids (e.g. reading stones) and 53% needed electronic magnifying aids, such as screen magnifiers or camera reading systems. Particularly for children, the use of magnifying aids for reading is essential for education in schools and 73% of the children used optical or electronic devices for reading. Of the children 52% attended a mainstream school and were additionally supported by special

  12. Emotion causes targeted forgetting of established memories

    Directory of Open Access Journals (Sweden)

    Bryan A. Strange

    2010-11-01

    Full Text Available Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least six days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval.

  13. Throwing the dart blind-folded: comparison of computed tomography versus magnetic resonance imaging-guided brachytherapy for cervical cancer with regard to dose received by the ‘actual’ targets and organs at risk

    Science.gov (United States)

    Wong, Joyce Siu Yu; Lee, Venus Wan Yan; Wong, Frank Chi Sing; Tung, Stewart Yuk

    2017-01-01

    Purpose Computed tomography (CT) is inferior to magnetic resonance imaging (MRI) in cervical tumor delineation, but similar in identification of organs at risk (OAR). The trend to over-estimate high-risk and low-risk clinical target volume (HRCTV, IRCTV) on CT can lead to under-estimation of dose received by 90% (D90) of the ‘actual’ CTV. This study aims to evaluate whether CT-guided planning delivers adequate dose to the ‘actual’ targets while spares the OAR similarly. Material and methods MRI-guided high-dose-rate image-guided brachytherapy (IGBT) was performed in 11 patients. The pre-brachytherapy CTs were retrospectively contoured to generate CT-guided plans. MRI-based contours (HRCTVmri, IRCTVmri, bladdermri, rectummri, and sigmoidmri) were fused to CT plans for dosimetric comparison with MRI-guided plans. Paired 2-tailed t-test and Wilcoxon signed-rank test were used to analyze data. Results 63.6% of CT plans achieved the HRCTVmriD90 constraint (≥ 7.2 Gy in one fraction), compared with 90.9% for MRI plans. > 90% of both modalities achieved the OAR’s constraints (EMBRACE). The percentage of CT and MRI plans that achieved the aims (EMBRACE II) for bladder, rectum, and sigmoid were 36.4% vs. 81.8%, 63.6% vs. 63.6%, and 72.7% vs. 72.7%, respectively. There were no statistically significant differences in HRCTVmriD90, IRCTVmriD90, or dose received by the most exposed 2 cm3 (D2cc) of OARmri between the modalities. Excluding the CT plans not achieving HRCTVmriD90 constraint, there were significant increase in bladdermriD2cc, rectummriD2cc, and sigmoidmriD2cc, compared with MRI plans (0.9 Gy/Fr, 95% CI 0.2-1.5, p = 0.018; 0.9 Gy/Fr, 95% CI 0.3-1.4, p = 0.009; 0.5 Gy/Fr, 95% CI 0.2-0.9, p = 0.027, respectively). Conclusions MRI-based IGBT remains the gold standard. CT planning may compromise HRCTVmriD90 or increase OARmriD2cc, which could decrease local control or increase treatment toxicity. PMID:29204165

  14. Volunteering Is Associated with Lower Risk of Cognitive Impairment.

    Science.gov (United States)

    Infurna, Frank J; Okun, Morris A; Grimm, Kevin J

    2016-11-01

    To examine whether psychosocial factors that can be a target for interventions, such as volunteering, are associated with risk of cognitive impairment. Health and Retirement Study (HRS) data from 1998 to 2012, a nationally representative longitudinal panel survey of older adults assessed every 2 years, were used. The HRS interviews participants aged 50 and older across the contiguous United States. Individuals aged 60 and older in 1998 (N = 13,262). Personal interviews were conducted with respondents to assess presence of cognitive impairment, measured using a composite across cognitive measures. Volunteering at the initial assessment and volunteering regularly over time independently decreased the risk of cognitive impairment over 14 years, and these findings were maintained independent of known risk factors for cognitive impairment. Greater risk of onset of cognitive impairment was associated with being older, being female, being nonwhite, having fewer years of education, and reporting more depressive symptoms. Consistent civic engagement in old age is associated with lower risk of cognitive impairment and provides impetus for interventions to protect against the onset of cognitive impairment. Given the increasing number of baby boomers entering old age, the findings support the public health benefits of volunteering and the potential role of geriatricians, who can promote volunteering by incorporating "prescriptions to volunteer" into their patient care. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  15. Behavioral Syndromes in Mild Cognitive Impairment and Alzheimer's Disease

    NARCIS (Netherlands)

    Van der Mussele, Stefan; Marien, Peter; Saerens, Jos; Somers, Nore; Goeman, Johan; De Deyn, Peter P.; Engelborghs, Sebastiaan

    2014-01-01

    Background: Behavioral disturbances belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI). The identification of sets of symptoms is clinically interesting, as interventions targeting syndromes may be more effective than the management of individual symptoms.

  16. [Multilingualism and specific language impairment].

    Science.gov (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  17. Persistently better treatment planning results of intensity-modulated (IMRT) over conformal radiotherapy (3D-CRT) in prostate cancer patients with significant variation of clinical target volume and/or organs-at-risk

    International Nuclear Information System (INIS)

    Fenoglietto, Pascal; Laliberte, Benoit; Allaw, Ali; Ailleres, Norbert; Idri, Katia; Hay, Meng Huor; Moscardo, Carmen Llacer; Gourgou, Sophie; Dubois, Jean-Bernard; Azria, David

    2008-01-01

    Purpose: To compare the dose coverage of planning and clinical target volume (PTV, CTV), and organs-at-risk (OAR) between intensity-modulated (3D-IMRT) and conventional conformal radiotherapy (3D-CRT) before and after internal organ variation in prostate cancer. Methods and materials: We selected 10 patients with clinically significant interfraction volume changes. Patients were treated with 3D-IMRT to 80 Gy (minimum PTV dose of 76 Gy, excluding rectum). Fictitious, equivalent 3D-CRT plans (80 Gy at isocenter, with 95% isodose (76 Gy) coverage of PTV, with rectal blocking above 76 Gy) were generated using the same planning CT data set ('CT planning'). The plans were then also applied to a verification CT scan ('CT verify') obtained at a different moment. PTV, CTV, and OAR dose coverage were compared using non-parametric tests statistics for V95, V90 (% of the volume receiving ≥95 or 90% of the dose) and D50 (dose to 50% of the volume). Results: Mean V95 of the PTV for 'CT planning' was 94.3% (range, 88-99) vs 89.1% (range, 84-94.5) for 3D-IMRT and 3D-CRT (p = 0.005), respectively. Mean V95 of the CTV for 'CT verify' was 97% for both 3D-IMRT and 3D-CRT. Mean D50 of the rectum for 'CT planning' was 26.8 Gy (range, 22-35) vs 43.5 Gy (range, 33.5-50.5) for 3D-IMRT and 3D-CRT (p = 0.0002), respectively. For 'CT verify', this D50 was 31.1 Gy (range, 16.5-44) vs 44.2 Gy (range, 34-55) for 3D-IMRT and 3D-CRT (p = 0.006), respectively. V95 of the rectum was 0% for both plans for 'CT planning', and 2.3% (3D-IMRT) vs 2.1% (3D-CRT) for 'CT verify' (p = non-sig.). Conclusion: Dose coverage of the PTV and OAR was better with 3D-IMRT for each patient and remained so after internal volume changes

  18. Oxidation of multiple methionine residues impairs rapid sodium channel inactivation

    Science.gov (United States)

    Kassmann, Mario; Hansel, Alfred; Leipold, Enrico; Birkenbeil, Jan; Lu, Song-Qing; Hoshi, Toshinori; Heinemann, Stefan H.

    2010-01-01

    Reactive oxygen species (ROS) readily oxidize the sulfur-containing amino acids cysteine and methionine (Met). The impact of Met oxidation on the fast inactivation of the skeletal muscle sodium channel NaV1.4 expressed in human embryonic kidney cells was studied by applying the Met-preferring oxidant chloramine-T (ChT) or by irradiating the ROS-producing dye Lucifer Yellow in the patch pipettes. Both interventions dramatically slowed down inactivation of the sodium channels. Replacement of Met in the Ile-Phe-Met inactivation motif with Leu (M1305L) strongly attenuated the oxidizing effect on inactivation but did not eliminate it completely. Mutagenesis of conserved Met residues in the intracellular linkers connecting the membrane-spanning segments of the channel (M1469L and M1470L) also markedly diminished the oxidation sensitivity of the channel, while that of other conserved Met residues (442, 1139, 1154, 1316) were without any noticeable effect. The results of mutagenesis of results, assays of other NaV channel isoforms (NaV1.2, NaV1.5, NaV1.7) and the kinetics of the oxidation-induced removal of inactivation collectively indicate that multiple Met target residues need to be oxidized to completely impair inactivation. This arrangement using multiple Met residues confers a finely graded oxidative modulation of NaV channels and allows organisms to adapt to a variety of oxidative stress conditions, such as ischemic reperfusion. PMID:18369661

  19. Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets.

    Science.gov (United States)

    Gisslén, M; Svedhem, V; Lindborg, L; Flamholc, L; Norrgren, H; Wendahl, S; Axelsson, M; Sönnerborg, A

    2017-04-01

    The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV-1-infected population in Sweden. The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV-1 in Sweden by 31 December 2015. Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV-infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90-90-90 goals. © 2016 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  20. Relationship between target organ damage and blood pressure, retinal vessel calibre, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes in patients with hypertension: a case-control study protocol (LOD-Hipertension).

    Science.gov (United States)

    Gomez-Marcos, Manuel A; Gonzalez-Sarmiento, Rogelio; Recio-Rodríguez, José I; Agudo-Conde, Cristina; Gamella-Pozuelo, Luis; Perretta-Tejedor, Nuria; Martínez-Salgado, Carlos; García-Ortiz, Luis

    2014-04-03

    Target organ damage (TOD) is associated with increased cardiovascular risk. The study objectives were to analyse the relationship of TOD to blood pressure, size of retinal arteries and veins, oxidative stress and different polymorphisms in the VAV-2 and VAV-3 genes in participants with hypertension. A case-control study to analyse the relationship between clinical, biochemical and genetic parameters and presence of cardiac, vascular and renal TOD in 486 patients with hypertension. Participants with TOD will be considered as cases, and those without TOD will be enrolled as controls. This will be a collaborative study conducted by the groups of Primary Care, Cardiovascular and Metabolic and Degenerative Diseases of the Instituto de Investigación Biomédica of Salamanca (IBSAL). Assessment of cardiac, renal and vascular TOD. Measurement of peripheral and central blood pressure, size of eye fundus arteries and veins, and oxidative stress, and polymorphisms in the VAV-2 and VAV-3 genes. The study will be conducted after approval is obtained from the Ethics Committee of Hospital Clínico Universitario of Salamanca. All study participants will sign an informed consent to agree to participate in the study, and another consent to agree on the genetic study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow for an understanding of the relationship of the different TODs with blood pressure, retinal artery and vein diameters, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes. Clinical Trials. gov Identifier: NCT02022618.

  1. Polarized scintillator targets

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2000-05-01

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as "live" polarized targets in nuclear physics experiments.

  2. Polarized scintillator targets

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B. van den E-mail: vandenbrandt@psi.ch; Bunyatova, E.I.; Hautle, P.; Konter, J.A.; Mango, S

    2000-05-21

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as 'live' polarized targets in nuclear physics experiments.

  3. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your...

  4. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your disability is...

  5. Making Sense of Mild Cognitive Impairment: A Qualitative Exploration of the Patient's Experience

    Science.gov (United States)

    Lingler, Jennifer Hagerty; Nightingale, Marcie C.; Erlen, Judith A.; Kane, April L.; Reynolds, Charles F.; Schulz, Richard; DeKosky, Steven T.

    2006-01-01

    Purpose: The proposed dementia precursor state of mild cognitive impairment is emerging as a primary target of aging research. Yet, little is known about the subjective experience of living with a diagnosis of mild cognitive impairment. This study examines, from the patient's perspective, the experience of living with and making sense of the…

  6. Association Between Sensory Impairment and Dementia in Older Adults: Evidence from China.

    Science.gov (United States)

    Luo, Yanan; He, Ping; Guo, Chao; Chen, Gong; Li, Ning; Zheng, Xiaoying

    2018-01-10

    To determine the association between sensory impairment and dementia in Chinese older adults. Cross-sectional. Older adults in 31 provinces of China. Individuals aged 65 and older (N = 250,752). Psychiatrists ascertained dementia based on the International Classification of Diseases, 10th Revision. Sensory impairment was measured as only hearing impairment, only vision impairment, and combined sensory impairment (combined hearing and vision impairment). Hearing impairment was defined as greater than 40 dB loss in the better ear according to the standard of the World Health Organization (WHO) Prevention of Deafness and Hearing Impairment (PDH) standard 97.3. Ophthalmologists assessed vision impairment according to the WHO best-corrected visual acuity (BCVA) criteria (low vision: 0.05≤BCVA ≤0.29; blindness: no light perception ≤ BCVA dementia was 0.41% (95% CI = 0.39-0.44%) without sensory impairment, 0.83% (95% CI = 0.70-0.99%) with only visual impairment, 0.61 (95% CI = 0.53-0.71%) with only hearing impairment, and 1.27% (95% CI = 1.00-1.61%) with combined sensory impairments. After adjusting for sociodemographic characteristics, vision impairment (odds ratio (OR) = 1.58, 95% CI = 1.28-1.96) and combined sensory impairments (OR = 1.64, 95% CI = 1.23-2.20) were associated with greater risk of severe to extremely severe dementia. Hearing impairment was not significantly associated with dementia. Sensory impairments are associated with greater risk of dementia in Chinese older adults. Studies are needed to further explore the pathway of this association in Chinese elderly adults and to provide suggestions to improve health status for this population. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

  7. Impaired picture recognition in transient epileptic amnesia.

    Science.gov (United States)

    Dewar, Michaela; Hoefeijzers, Serge; Zeman, Adam; Butler, Christopher; Della Sala, Sergio

    2015-01-01

    Transient epileptic amnesia (TEA) is an epileptic syndrome characterized by recurrent, brief episodes of amnesia. Transient epileptic amnesia is often associated with the rapid decline in recall of new information over hours to days (accelerated long-term forgetting - 'ALF'). It remains unknown how recognition memory is affected in TEA over time. Here, we report a systematic study of picture recognition in patients with TEA over the course of one week. Sixteen patients with TEA and 16 matched controls were presented with 300 photos of everyday life scenes. Yes/no picture recognition was tested 5min, 2.5h, 7.5h, 24h, and 1week after picture presentation using a subset of target pictures as well as similar and different foils. Picture recognition was impaired in the patient group at all test times, including the 5-minute test, but it declined normally over the course of 1week. This impairment was associated predominantly with an increased false alarm rate, especially for similar foils. High performance on a control test indicates that this impairment was not associated with perceptual or discrimination deficits. Our findings suggest that, at least in some TEA patients with ALF in verbal recall, picture recognition does not decline more rapidly than in controls over 1week. However, our findings of an early picture recognition deficit suggest that new visual memories are impoverished after minutes in TEA. This could be the result of deficient encoding or impaired early consolidation. The early picture recognition deficit observed could reflect either the early stages of the process that leads to ALF or a separable deficit of anterograde memory in TEA. Lastly, our study suggests that at least some patients with TEA are prone to falsely recognizing new everyday visual information that they have not in fact seen previously. This deficit, alongside their ALF in free recall, likely affects everyday memory performance. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Pelvic floor dysfunction and sensory impairment: Current evidence.

    Science.gov (United States)

    Mahoney, Charlotte; Smith, Anthony; Marshall, Andy; Reid, Fiona

    2017-03-01

    To explore the role of sensory nerve impairment in women with pelvic organ prolapse, painful bladder syndrome, urinary and fecal incontinence, and sexual dysfunction. Medline and Embase were searched for articles in which sensory testing, either quantitative sensory testing or current perception thresholds, had been used to evaluate women with pelvic organ prolapse, stress and urge urinary incontinence, fecal incontinence and female sexual dysfunction. All search terms were expanded within each database prior to searching. Research to date has included small numbers of participants, used poorly matched controls, lacked a systemic sensory examination and applied non-standardized sensory testing techniques. However, the evidence suggests women with pelvic organ prolapse demonstrate sensory dysfunction. The role of sensory impairment in stress urinary incontinence is inconclusive. In women with urge urinary incontinence there is some evidence to suggest it may be urethrally mediated. Women with painful bladder syndrome may have more sensitive nerve endings which are unable to ignore repeated stimuli. Sensory impairment is common in women with sexual dysfunction, typically involving larger nerve fibres. There were no studies evaluating sensory function in women with fecal incontinence. Current evidence suggests women with pelvic floor dysfunction demonstrate sensory impairment though the causes remain unclear. Further studies are needed to investigate the different conditions of pelvic floor dysfunction using standardized sensory testing techniques, as well as evaluate the timing and mechanism by which any sensory impairment develops. Neurourol. Urodynam. 36:550-556, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Nutrition and cognitive impairment

    Science.gov (United States)

    Hernando-Requejo, Virgilio

    2016-07-12

    Dementia, closely linked to environmental predisposing factors such as diet, is a public health problem of increasing magnitude: currently there are more than 35 million patients with Alzheimer´s disease, and is expected to exceed 135 million by 2050. If we can delay the development of dementia 5 years will reduce its prevalence by 50%. Patients with dementia modify their diet, and it has been reported in them deficits, among others, of folic acid, vitamin B12, B6, C, E, A, D, K, beta carotene and omega 3 fatty acids, that must be resolved with proper diet and with extra contributions if needed in some cases. But to reduce, or at least delay, the prevalence of dementia we advocate prevention through proper diet from the beginning of life, an idea that is reinforced given that cardiovascular risk factors are related directly to the development of dementia. A lot of literature are available that, although with limits, allows us to make nutritional recommendations for preventing cognitive impairment. Better results are achieved when complete diets have been studied and considered over specific nutrients separately. Particularly, the Mediterranean diet has great interest in this disease, since it ensures a high intake of vegetables, fruits, nuts, legumes, cereals, fish and olive oil, and moderate intake of meat, dairy products and alcohol. We will focus more on this article in this type of diet.

  10. Organization within Organization Studies

    DEFF Research Database (Denmark)

    Lopdrup-Hjorth, Thomas

    This paper explores how prevalent contemporary problematizations of organizations coincide with a widespread assessment that Organization Studies (OS) has run out of steam. This impasse, the paper argues, is largely due to the emergence of an organization-phobia that has come to seize several...... strands of theorizing. By attending to the wide-ranging and far-reaching history of this organization-phobia, the paper argues that OS has become increasingly incapable of speaking about its core object. I show how organizations went from being conceptualized as entities of major importance to becoming...... credibility and legitimacy to begin with, the organization-phobia resulting from this history has been implicated in dismantling organizations, and in making OS progressively irrelevant to a wider public....

  11. Recurring Utterances - Targeting a Breakthrough

    Directory of Open Access Journals (Sweden)

    Jacqueline Stark

    2014-05-01

    The most interesting phenomenon is KB’s production of words from former sessions indicating that they are still ‘active’ and the production of completely novel incorrect words. The observable features indicate that immediate auditory processing is possible in the form of repeating target words. However, as soon as KB must retrieve information from the (semantic lexicon, even after being able to correctly ‘repeat’ the target word several times, he responds with a RU, perseveration, or paraphasia. Several of his productions can be characterized as aphasic confabulations which stem from a memory gap. Thus, although KB’s language impairment is severe, his responses across time indicate that step-by-step a breakthrough is being made.

  12. A framework for communication between visually impaired, hearing impaired and speech impaired using arduino

    Science.gov (United States)

    Sujatha, R.; Khandelwa, Prakhar; Gupta, Anusha; Anand, Nayan

    2017-11-01

    A long time ago our society accepted the notion of treating people with disabilities not as unviable and disabled but as differently-abled, recognizing their skills beyond their disabilities. The next step has to be taken by our scientific community, that is, to normalize lives of the people with disabilities and make it so as if they are no different to us. The primary step in this direction would be to normalize communication between people. People with an impaired speech or impaired vision or impaired hearing face difficulties while having a casual conversation with others. Any form of communication feels so strenuous that the impaired end up communicating just the important information and avoid a casual conversation. To normalize conversation between the impaired we need a simple and compact device which facilitates the conversation by providing the information in the desired form.

  13. Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols.

    Science.gov (United States)

    Meenach, Samantha A; Vogt, Frederick G; Anderson, Kimberly W; Hilt, J Zach; McGarry, Ronald C; Mansour, Heidi M

    2013-01-01

    Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 nm to 1.2 μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 μm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the

  14. Superior and efficiency sport of visually impaired people in the Czech Republic

    OpenAIRE

    Trnka, Václav

    2008-01-01

    Project: Superior and efficiency sport of visually impaired people in the Czech Republic Aim of the project: The aim of the project is to compile an overview about Paralympic and selected sports that are done by visually impaired people here in the Czech Republic. The overview includes basic information about specification of individual sports of visually impaired persons as well as updated description of organization of sports for such disabled persons. Based on these facts it makes suggesti...

  15. An overview of motor skill performance and balance in hearing impaired children

    Directory of Open Access Journals (Sweden)

    Roy Finita

    2011-07-01

    Full Text Available Abstract Childhood hearing impairment is a common chronic condition that may have a major impact on acquisition of speech, social and physical development. Numerous literature states that injury to the vestibular organs may result in accompanying balance and motor development disorders. But still postural control and motor assessments are not a routine procedure in hearing impaired children. Hence, we aim to provide an overview on motor skill performance and balance in hearing impaired children.

  16. Polarized Scintillating Targets at Psi

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2001-02-01

    Scintillating polarized targets are now routinely available: blocks of 18×18×5 mm scintillating organic polymer, doped with TEMPO, polarized dynamically in a field of 2.5 T in a vertical 3He-4He dilution refrigerator. A 19 mm diameter plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat.

  17. Multiple Learning Strategies Project. Building Maintenance & Engineering. Visually Impaired.

    Science.gov (United States)

    Smith, Dwight; And Others

    This instructional package is designed for visually impaired students in the vocational area of building maintenance and engineering. The twenty-eight learning modules are organized into six units: floor care, general maintenance tasks; restrooms; carpet care; power and hand tools; and cabinet construction. Each module, printed in large block…

  18. Functional Problems of the Visually Impaired: A Research Approach.

    Science.gov (United States)

    Bikson, Thomas H.; Bikson, Tora K.

    Capabilities and limitations of 251 severely visually impaired persons (senior high school age or older) were assessed on a range of visual environmental adaptation problems to learn how they are organized and influenced. Factor analyses indicated that problems can be grouped on the basis of eight functional domains, among which an independent…

  19. 20 CFR 220.145 - Impairment-related work expenses.

    Science.gov (United States)

    2010-04-01

    ... internal body organ or external body part. Examples of prosthetic devices are artificial replacements of... at home, any cost deducted as a business expense cannot be deducted as an impairment-related work... non-purified air environment. An item such as an exercycle is not deductible if used for general...

  20. Multiple Learning Strategies Project. Medical Assistant. Visually Impaired. [Vol. 1.

    Science.gov (United States)

    Varney, Beverly; And Others

    This instructional package, one of two designed for visually impaired students, focuses on the vocational area of medical assistant. Contained in this document are twelve learning modules organized into five units: language; receptioning; asepsis; supplies and equipment maintenance; and diagnostic tests. Each module, printed in block type,…

  1. Multiple Learning Strategies Project. Small Engine Repair. Visually Impaired.

    Science.gov (United States)

    Foster, Don; And Others

    This instructional package designed for visually impaired students, focuses on the vocational area of small engine repair. Contained in this document are forty learning modules organized into fourteen units: engine block; starters; fuel tank, lines, filters and pumps; carburetors; electrical; test equipment; motorcycle; machining; tune-ups; short…

  2. Brain visual impairment in childhood: mini review

    OpenAIRE

    Kozeis, N

    2010-01-01

    Cerebral visual impairment (CVI) is one of the leading causes of severe visual impairment in childhood. This article was written to highlight any new knowledge related to cerebral visual impairment in childhood.

  3. Characterisation of Physical Frailty and Associated Physical and Functional Impairments in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Ma Shwe Zin Nyunt

    2017-12-01

    Full Text Available ObjectiveTo characterize the physical frailty phenotype and its associated physical and functional impairments in mild cognitive impairment (MCI.MethodParticipants with MCI (N = 119, normal low cognition (NLC, N = 138, and normal high cognition (NHC, N = 1,681 in the Singapore Longitudinal Ageing Studies (SLAS-2 were compared on the prevalence of physical frailty, low lean body mass, weakness, slow gait, exhaustion and low physical activity, and POMA balance and gait impairment and fall risk.ResultsThere were significantly higher prevalence of frailty in MCI (18.5%, than in NLC (8.0% and NHC (3.9%, and pre-frailty in MCI (54.6%, NLC (52.9% than in NHC (48.0%. Age, sex, and ethnicity-adjusted OR (95% CI of association with MCI (versus NHC for frailty were 4.65 (2.40–9.04 and for pre-frailty, 1.67 (1.07–2.61. Similar significantly elevated prevalence and adjusted ORs of association with MCI were observed for frailty-associated physical and functional impairments. Further adjustment for education, marital status, living status, comorbidities, and GDS significantly reduced the OR estimates. However, the OR estimates remained elevated for frailty: 3.86 (1.83–8.17, low body mass: 1.70 (1.08–2.67, slow gait: 1.84 (1.17–2.89, impaired gait: 4.17 (1.98–8.81, and elevated fall risk 3.42 (1.22–9.53.ConclusionTwo-thirds of MCI were physically frail or pre-frail, most uniquely due to low lean muscle mass, slow gait speed, or balance and gait impairment. The close associations of frailty and physical and functional impairment with MCI have important implications for improving diagnostic acuity of MCI and targetting interventions among cognitively frail individuals to prevent dementia and disability.

  4. Verbal memory impairments in schizophrenia associated with cortical thinning

    Directory of Open Access Journals (Sweden)

    S. Guimond

    2016-01-01

    Full Text Available Verbal memory (VM represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with ‘moderate to severe’ VM impairments were compared to 23 patients with ‘low to mild’ VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with ‘moderate to severe’ VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with ‘low to mild’ VM impairments, patients with ‘moderate to severe’ VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with ‘low to mild’ VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments.

  5. Specific Language Impairment in Families: Evidence for Co-Occurrence with Reading Impairments.

    Science.gov (United States)

    Flax, Judy F.; Realpe-Bonilla, Teresa; Hirsch, Linda S.; Brzustowicz, Linda M.; Bartlett, Christopher W.; Tallal, Paula

    2003-01-01

    Two family aggregation studies involving 25 children (ages 5-10) with specific language impairment (SLI) report the occurrence and co-occurrence of oral language impairments and reading impairments. Results indicate that when language impairments occur within families of SLI probands, these impairments generally co-occur with reading impairments.…

  6. Genetic Counseling in Hearing Impairment.

    Science.gov (United States)

    Fraser, George R.

    1979-01-01

    The problem of counseling is dealt with mainly in the context of severe hearing impairment, since moderate forms are often due to illness or other nongenetic factors and do not constitute a grave handicap. (DLS)

  7. The ICF: A Framework for Setting Goals for Children with Speech Impairment

    Science.gov (United States)

    McLeod, Sharynne; Bleile, Ken

    2004-01-01

    The International Classification of Functioning, Disability and Health (ICF) (World Health Organization, 2001) is proposed as a framework for integrative goal setting for children with speech impairment. The ICF incorporates both impairment and social factors to consider when selecting appropriate goals to bring about change in the lives of…

  8. 38 CFR 4.75 - General considerations for evaluating visual impairment.

    Science.gov (United States)

    2010-07-01

    ... evaluations for other disabilities of the same eye that are not based on visual impairment (e.g... for evaluating visual impairment. 4.75 Section 4.75 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Organs of Special Sense...

  9. Organization within Organization Studies

    DEFF Research Database (Denmark)

    Lopdrup-Hjorth, Thomas

    strands of theorizing. By attending to the wide-ranging and far-reaching history of this organization-phobia, the paper argues that OS has become increasingly incapable of speaking about its core object. I show how organizations went from being conceptualized as entities of major importance to becoming...

  10. Knowledge Organization = Information Organization?

    DEFF Research Database (Denmark)

    Hjørland, Birger

    Are the terms ―information organization‖ (IO), ―organization of information‖ (OI) and ―information architecture‖ (IA) synonyms for knowledge organization (KO)? This study uses bibliometric methods, among others, to determine some relations between these terms and their meanings. Apparently the data...

  11. Emotional impairment in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    CHEN Hai-bo

    2013-08-01

    Full Text Available Emotional impairment is the common complication of Parkinson's disease (PD. Depression, anxiety and apathy affect the quality of life and the prognosis of PD patients. Neuropsychological and neuroimaging studies of emotional impairment in PD patients suggest abnormalities involving mesolimbic and mesocortical dopaminergic pathways, but the specific mechanism needs further study. In this review we discuss the clinical manifestation, possible pathological mechanism, diagnosis and treatment in PD patients.

  12. Impaired tooth eruption: a review.

    Science.gov (United States)

    Noffke, C E E; Chabikuli, N J; Nzima, N

    2005-11-01

    Eruption is the continuous process of movement of a tooth from its developmental location inside the jaw to its functional location in the mouth. Impaired tooth eruption, where this process is disturbed, is common in dental practice. It may manifest either as delayed or complete absence of eruption. Although unerupted teeth are usually asymptomatic, they may cause cosmetic and pathologic complications. The purpose of this article is to provide a review on the pathogenesis and differential radiographic interpretation of impaired tooth eruption.

  13. [Sampling and measurement methods of the protocol design of the China Nine-Province Survey for blindness, visual impairment and cataract surgery].

    Science.gov (United States)

    Zhao, Jia-liang; Wang, Yu; Gao, Xue-cheng; Ellwein, Leon B; Liu, Hu

    2011-09-01

    To design the protocol of the China nine-province survey for blindness, visual impairment and cataract surgery to evaluate the prevalence and main causes of blindness and visual impairment, and the prevalence and outcomes of the cataract surgery. The protocol design was began after accepting the task for the national survey for blindness, visual impairment and cataract surgery from the Department of Medicine, Ministry of Health, China, in November, 2005. The protocol in Beijing Shunyi Eye Study in 1996 and Guangdong Doumen County Eye Study in 1997, both supported by World Health Organization, was taken as the basis for the protocol design. The relative experts were invited to discuss and prove the draft protocol. An international advisor committee was established to examine and approve the draft protocol. Finally, the survey protocol was checked and approved by the Department of Medicine, Ministry of Health, China and Prevention Program of Blindness and Deafness, WHO. The survey protocol was designed according to the characteristics and the scale of the survey. The contents of the protocol included determination of target population and survey sites, calculation of the sample size, design of the random sampling, composition and organization of the survey teams, determination of the examinee, the flowchart of the field work, survey items and methods, diagnostic criteria of blindness and moderate and sever visual impairment, the measures of the quality control, the methods of the data management. The designed protocol became the standard and practical protocol for the survey to evaluate the prevalence and main causes of blindness and visual impairment, and the prevalence and outcomes of the cataract surgery.

  14. Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC and dipalmitoylphosphatidylethanolamine poly(ethylene glycol (DPPE-PEG microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

    Directory of Open Access Journals (Sweden)

    Meenach SA

    2013-01-01

    Full Text Available Samantha A Meenach,1,2 Frederick G Vogt,3 Kimberly W Anderson,2,4 J Zach Hilt,2,4 Ronald C McGarry,5Heidi M Mansour1,41Department of Pharmaceutical Sciences-Drug Development Division, University of Kentucky College of Pharmacy, Lexington, KY; 2Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY, USA; 3Analytical Sciences, Product Development, GlaxoSmithKline, King of Prussia, PA; 4Center of Membrane Sciences, University of Kentucky, Lexington, KY, 5Department of Radiation Medicine, University of Kentucky College of Medicine, Lexington, KY, USAAbstract: Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol (PEGylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 nm to 1.2 μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC and powder X-ray diffraction (PXRD were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated

  15. Assessing functional impairment in individuals with mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Patrícia Belchior

    2016-04-01

    Full Text Available To date, there is no consensus on how to assess functional impairment in individuals with mild cognitive impairment (MCI, and this lack of consensus is reflected in the clinical practice. Since the criterion used in the literature is very vague, clinicians are still left without much guidance in this area. Thus, the main goal of this study was to examine how functional impairment in individuals with MCI has been assessed in the literature. An electronic database search strategy was developed in consultation with an experienced librarian. Four databases (CINAHL, PsycINFO, PubMed, and MEDLINE were searched from 2000 to May 2014 to provide a comprehensive coverage of the literature. The literature search yielded 14 tools that assessed functional impairment in MCI. Among those, nine tools were performance-based measures in which participants were observed while executing a task in a simulated environment using real life material. In terms of questionnaires (either informant- or self-reports, five tools were found. Different functional domains have been assessed in each tool. According to this review, the characteristics of the instruments used in the literature to assess functional impairment in individuals with MCI vary greatly. Nonetheless, results of this study allow clinicians to make better-informed decisions when choosing a functional assessment for this population.

  16. Arterial stiffness and cognitive impairment.

    Science.gov (United States)

    Li, Xiaoxuan; Lyu, Peiyuan; Ren, Yanyan; An, Jin; Dong, Yanhong

    2017-09-15

    Arterial stiffness is one of the earliest indicators of changes in vascular wall structure and function and may be assessed using various indicators, such as pulse-wave velocity (PWV), the cardio-ankle vascular index (CAVI), the ankle-brachial index (ABI), pulse pressure (PP), the augmentation index (AI), flow-mediated dilation (FMD), carotid intima media thickness (IMT) and arterial stiffness index-β. Arterial stiffness is generally considered an independent predictor of cardiovascular and cerebrovascular diseases. To date, a significant number of studies have focused on the relationship between arterial stiffness and cognitive impairment. To investigate the relationships between specific arterial stiffness parameters and cognitive impairment, elucidate the pathophysiological mechanisms underlying the relationship between arterial stiffness and cognitive impairment and determine how to interfere with arterial stiffness to prevent cognitive impairment, we searched PUBMED for studies regarding the relationship between arterial stiffness and cognitive impairment that were published from 2000 to 2017. We used the following key words in our search: "arterial stiffness and cognitive impairment" and "arterial stiffness and cognitive impairment mechanism". Studies involving human subjects older than 30years were included in the review, while irrelevant studies (i.e., studies involving subjects with comorbid kidney disease, diabetes and cardiac disease) were excluded from the review. We determined that arterial stiffness severity was positively correlated with cognitive impairment. Of the markers used to assess arterial stiffness, a higher PWV, CAVI, AI, IMT and index-β and a lower ABI and FMD were related to cognitive impairment. However, the relationship between PP and cognitive impairment remained controversial. The potential mechanisms linking arterial stiffness and cognitive impairment may be associated with arterial pulsatility, as greater arterial pulsatility

  17. Torcetrapib impairs endothelial function in hypertension.

    Science.gov (United States)

    Simic, Branko; Hermann, Matthias; Shaw, Sidney G; Bigler, Laurent; Stalder, Urs; Dörries, Carola; Besler, Christian; Lüscher, Thomas F; Ruschitzka, Frank

    2012-07-01

    A marked increase in HDL notwithstanding, the cholesterol ester transfer protein (CETP) inhibitor torcetrapib was associated with an increase in all-cause mortality in the ILLUMINATE trial. As underlying mechanisms remain elusive, the present study was designed to delineate potential off-target effects of torcetrapib. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were treated with torcetrapib (100 mg/kg/day; SHR-T and WKY-T) or placebo (SHR-P and WKY-P) for 3 weeks. Blood pressure transiently increased during the first 3 days of torcetrapib administration in SHRs and returned to baseline thereafter despite continued drug administration. Acetylcholine-induced endothelium-dependent relaxations of aortic rings were markedly impaired, and endothelial nitric oxide synthase (eNOS) mRNA and protein were down-regulated after 3 weeks of torcetrapib treatment in SHR (P risk is exposed to these compounds.

  18. Smart-system of distance learning of visually impaired people based on approaches of artificial intelligence

    Science.gov (United States)

    Samigulina, Galina A.; Shayakhmetova, Assem S.

    2016-11-01

    Research objective is the creation of intellectual innovative technology and information Smart-system of distance learning for visually impaired people. The organization of the available environment for receiving quality education for visually impaired people, their social adaptation in society are important and topical issues of modern education.The proposed Smart-system of distance learning for visually impaired people can significantly improve the efficiency and quality of education of this category of people. The scientific novelty of proposed Smart-system is using intelligent and statistical methods of processing multi-dimensional data, and taking into account psycho-physiological characteristics of perception and awareness learning information by visually impaired people.

  19. Patterns of Semantic Memory Impairment in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Sven Joubert

    2008-01-01

    Full Text Available Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment. The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

  20. Toxoplasma gondii impairs memory in infected seniors.

    Science.gov (United States)

    Gajewski, Patrick D; Falkenstein, Michael; Hengstler, Jan G; Golka, Klaus

    2014-02-01

    Almost 30% of humans present a Toxoplasma gondii positive antibody status and its prevalence increases with age. The central nervous system is the main target. However, little is known about the influence of asymptomatic i.e. latent Toxoplasmosis on cognitive functions in humans. To investigate neurocognitive dysfunctions in asymptomatic older adults with T. gondii positive antibody status a double-blinded neuropsychological study was conducted. The participants were classified from a population-based sample (N=131) of healthy participants with an age of 65 years and older into two groups with 42 individuals each: Toxoplasmosis positive (T-pos; IgG>50 IU/ml) and Toxoplasmosis negative (T-neg; IgG=0 IU/ml). The outcome measures were a computer-based working-memory test (2-back) and several standardized psychometric tests of memory and executive cognitive functions. T-pos seniors showed an impairment of different aspects of memory. The rate of correctly detected target symbols in a 2-back task was decreased by nearly 9% (P=0.020), corresponding to a performance reduction of about 35% in working memory relative to the T-neg group. Moreover, T-pos seniors had a lower performance in a verbal memory test, both regarding immediate recall (10% reduction; P=0.022), delayed recognition (6%; P=0.037) and recall from long-term memory assessed by the word fluency tests (12%; P=0.029). In contrast, executive functions were not affected. The effects remained mostly unchanged after controlling for medication. The impairment of memory functions in T-pos seniors was accompanied by a decreased self-reported quality of life. Because of the high prevalence of asymptomatic Toxoplasmosis and an increasing population of older adults this finding is of high relevance for public health. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. High blood pressure in older subjects with cognitive impairment.

    Science.gov (United States)

    Mossello, Enrico; Simoni, David

    2016-06-22

    High blood pressure and cognitive impairment often coexist in old age, but their pathophysiological association is complex. Several longitudinal studies have shown that high blood pressure at midlife is a risk factor for cognitive impairment and dementia, although this association is much less clear in old age. The effect of blood pressure lowering in reducing the risk of dementia is only borderline significant in clinical trials of older subjects, partly due to the insufficient follow-up time. Conversely, dementia onset is associated with a decrease of blood pressure values, probably secondary to neurodegeneration. Prognostic effect of blood pressure values in cognitively impaired older subjects is still unclear, with aggressive blood pressure lowering being potentially harmful in this patients category. Brief cognitive screening, coupled with simple motor assessment, are warranted to identify frail older subjects who need a more cautious approach to antihypertensive treatment. Values obtained with ambulatory blood pressure monitoring seem more useful than clinical ones to predict the outcome of cognitively impaired older subjects. Future studies should identify the most appropriate blood pressure targets in older subjects with cognitive impairment.

  2. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    areas typically affected by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum and thalamus that are relatively spared in Alzheimer's disease. The reduction of the serotonin transporter in mild cognitive impairment was greater than grey matter atrophy or reductions in regional cerebral blood flow compared to controls. Lower cortical serotonin transporters were associated with worse performance on tests of auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. The serotonin system may represent an important target for prevention and treatment of MCI, particularly the post-synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as presynaptic aspects of the serotonin system, as indicated by the observation of lower serotonin transporters in MCI relative to healthy controls. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Language Impairment and Generative Analysis

    Directory of Open Access Journals (Sweden)

    Andrej Stopar

    2004-12-01

    Full Text Available This article deals with different types of language impairment from the perspective of generative grammar. The paper focuses on syntactic deficiencies observed in aphasic and SLI (specific language impairment patients. We show that the observed ungrammatical structures do not appear in a random fashion but can be predicted by that theory of universal sentence structure which posits a strict hierarchy of its constituent parts. The article shows that while the hierarchically lower elements remain unaffected, the higher positions in the hierarchy show various degrees of syntactic impairment. The paper supports the implementation of recent developments in the field of generative grammar with the intention of encouraging further theoretical, experimental and therapeutic research in the field.

  4. [Behavioral impairments in Parkinson's disease].

    Science.gov (United States)

    Kashihara, Kenichi

    2004-09-01

    Behavioral impairments in parkinsonian patients include agitation, hypersexuality, stereotypic movement, pathological gambling, abuse of antiparkinsonian drugs, REM sleep behavioral disorder, and restless legs syndrome. Dementia, psychoses, and emotional disorders, such as depression and anxiety/panic disorder, also impair behavior. Symptoms may be produced by dysfunction of the central nervous system, medication, and/or the psychosocial problems associated with Parkinson's disease. Treatment therefore should be based on the cause of the symptoms seen. In some cases, the reduction or change of antiparkinsonian drugs, or both, may be effective. Treatment of the motor symptoms of Parkinson's disease, including motor fluctuations, may reduce the risk of panic attacks being evoked in the 'off' period. Use of antidepressants, sedatives, and neuroleptics may often be effective. Physicians should identify the causes of the symptoms of behavioral impairment and select appropriate treatments.

  5. Impaired immune function in seals and laboratory rats exposed to dioxin-like compounds from Baltic herring

    Energy Technology Data Exchange (ETDEWEB)

    Ross, P.S. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Swart, R.L. de [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands); Timmerman, H.H.; Loveren, H. van [National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Osterhaus, A.D.M.E. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands)

    1995-12-31

    Complex mixtures of lipophilic contaminants have been shown to affect certain top predators in the aquatic food chain, including seals. A recent demonstration that harbor seals (Phoca vitulina) fed Baltic Sea herring displayed impaired natural killer cell activity and T-lymphocyte function represented the first demonstration of immunotoxicity induced by ambient levels of contaminants in the environment. While these animals had a lower ability to respond to immunizations with inactivated vaccines, specific antibody responses, and in vitro antigen-specific lymphoproliferative responses, obvious constraints limited the ability to extend these results with host resistance tests or an evaluation of thymus and other lymphoid organs. The authors therefore set up a parallel study by exposing pregnant laboratory rats to the same Baltic herring contaminant mixture as received the seals. They then examined immune function parameters and host resistance to virus infection. As in the seals, rat pups of the Baltic group had impaired T-lymphocyte function. In addition, thymus cells and/or their precursors appeared to be targeted, as their numbers and function were reduced in the rats. Following challenge with rat cytomegalovirus in a host resistance study, rat pups in the Baltic group had impaired natural killer cell responses to the virus infection, and lower specific CD8 + (cytotoxic T-lymphocyte) responses following in vitro stimulation. By extrapolation, these results suggest that the impaired immune responses observed in the Baltic group of seals may lead to a less effective defense against virus infections in marine mammals inhabiting polluted coastal waters. Toxicological profiles and results of both the captive seal and laboratory rat experiments tend to implicate the 2,3,7,8-TCDD-like PCB, dioxin and furan congeners in the immunosuppression, and point to a major role for the PCBs.

  6. The biological basis of language: insight from developmental grammatical impairments.

    Science.gov (United States)

    van der Lely, Heather K J; Pinker, Steven

    2014-11-01

    Specific language impairment (SLI), a genetic developmental disorder, offers insights into the neurobiological and computational organization of language. A subtype, Grammatical-SLI (G-SLI), involves greater impairments in 'extended' grammatical representations, which are nonlocal, hierarchical, abstract, and composed, than in 'basic' ones, which are local, linear, semantic, and holistic. This distinction is seen in syntax, morphology, and phonology, and may be tied to abnormalities in the left hemisphere and basal ganglia, consistent with new models of the neurobiology of language which distinguish dorsal and ventral processing streams. Delineating neurolinguistic phenotypes promises a better understanding of the effects of genes on the brain circuitry underlying normal and impaired language abilities. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. [Pharmacological therapeutic intervention in mild cognitive impairment].

    Science.gov (United States)

    Arriola Manchola, Enrique; Alaba Loinaz, Javier

    2017-06-01

    Mild cognitive impairment (MCI) is a syndrome encompassing affective and behavioural symptoms and various subtypes. MCI is a heterogeneous clinical entity with varied causes (degenerative, vascular, psychiatric, non-neurological disorders), and there is wide variation in symptoms and clinical course. There are multiple causes and consequently various treatments can be applied and should be combined with non-pharmacological measures. This article describes both preventive and therapeutic pharmacological interventions: control of vascular risk factors, avoidance of iatrogeny, use of nutraceuticals, CDP-choline, and Ginkgo biloba EGb 761 ® , and improvement in sense organs. Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Unilateral vestibular loss impairs external space representation.

    Directory of Open Access Journals (Sweden)

    Liliane Borel

    Full Text Available The vestibular system is responsible for a wide range of postural and oculomotor functions and maintains an internal, updated representation of the position and movement of the head in space. In this study, we assessed whether unilateral vestibular loss affects external space representation. Patients with Menière's disease and healthy participants were instructed to point to memorized targets in near (peripersonal and far (extrapersonal spaces in the absence or presence of a visual background. These individuals were also required to estimate their body pointing direction. Menière's disease patients were tested before unilateral vestibular neurotomy and during the recovery period (one week and one month after the operation, and healthy participants were tested at similar times. Unilateral vestibular loss impaired the representation of both the external space and the body pointing direction: in the dark, the configuration of perceived targets was shifted toward the lesioned side and compressed toward the contralesioned hemifield, with higher pointing error in the near space. Performance varied according to the time elapsed after neurotomy: deficits were stronger during the early stages, while gradual compensation occurred subsequently. These findings provide the first demonstration of the critical role of vestibular signals in the representation of external space and of body pointing direction in the early stages after unilateral vestibular loss.

  9. Organ mass measurements

    International Nuclear Information System (INIS)

    Kawamura, H.

    1998-01-01

    The term, anatomical measurements, in the context of this Co-ordinated Research Programme refers to measurements of masses of internal organs, although the human body is composed of internal organs and tissues such as skeleton, muscle, skin and adipose. The mass of an organ containing a radionuclide (source organ), and the mass of a target organ which absorbs energy of the radiation, are essential parameters in the ICRP dosimetric model derived from the MIRD method. Twelve specific organs of interest were proposed at the Coordinated Research Programme Project Formulation Meeting (PFM) in 1988. A slightly different set of thirteen organs with potential significance for radiation protection were selected for study at the Research Co-ordination Meeting held at the Bhabha Atomic Research Centre in 1991. The dimensions of the organs could also be useful information, but were considered unimportant for internal dose assessment. Due to the strong concern about the unified method for collecting organ mass data at the PFM, a guide-line was established stressing the need for organ data from subjects that were healthy and normal, at least until shortly before death, or from sudden death cases, following the Japanese experience. In this report, masses of nine to thirteen organs are presented from seven participating countries. Three participants have also reported the organ masses as fractions of the total body mass

  10. Sensitivity of trunk variability and stability measures to balance impairments induced by galvanic vestibular stimulation during gait.

    NARCIS (Netherlands)

    van Schooten, K.S.; Sloot, L.H.; Bruijn, S.M.; Kingma, H; Meijer, O.G.; Pijnappels, M.A.G.M.; van Dieen, J.H.

    2011-01-01

    For targeted prevention of falls, it is necessary to identify individuals with balance impairments. To test the sensitivity of measures of variability, local stability and orbital stability of trunk kinematics to balance impairments during gait, we used galvanic vestibular stimulation (GVS) to

  11. Aging impairs recipient T cell intrinsic and extrinsic factors in response to transplantation.

    Directory of Open Access Journals (Sweden)

    Hua Shen

    Full Text Available As increasing numbers of older people are listed for solid organ transplantation, there is an urgent need to better understand how aging modifies alloimmune responses. Here, we investigated whether aging impairs the ability of donor dendritic cells or recipient immunity to prime alloimmune responses to organ transplantation.Using murine experimental models, we found that aging impaired the host environment to expand and activate antigen specific CD8(+ T cells. Additionally, aging impaired the ability of polyclonal T cells to induce acute allograft rejection. However, the alloimmune priming capability of donor dendritic cells was preserved with aging.Aging impairs recipient responses, both T cell intrinsic and extrinsic, in response to organ transplantation.

  12. Characteristics of functional impairment in patients with long-standing rheumatoid arthritis based on range of motion of joints: Baseline data from a multicenter prospective observational cohort study to evaluate the effectiveness of joint surgery in the treat-to-target era.

    Science.gov (United States)

    Kojima, Toshihisa; Ishikawa, Hajime; Tanaka, Sakae; Haga, Nobuhiko; Nishida, Keiichiro; Yukioka, Masao; Hashimoto, Jun; Miyahara, Hisaaki; Niki, Yasuo; Kimura, Tomoatsu; Oda, Hiromi; Asai, Shuji; Funahashi, Koji; Kojima, Masayo; Ishiguro, Naoki

    2017-07-25

    To explore the characteristics of functional impairment in patients with established rheumatoid arthritis (RA) based on the range of motion (ROM) of joints in a prospective observational study of RA patients undergoing joint surgery. We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and the ROM of large joints including the shoulder, elbow, wrist, hip, knee, and ankle. Associations between the ROM of each joint and disability in the eight HAQ-DI categories were determined using receiver operating characteristic (ROC) and logistic regression analyses. ROM cut-off values of each joint for the absence of disability in each HAQ-DI category were determined using ROC curves. A total of 460 patients were enrolled and analyzed in this study. Based on ROC analysis, the ROM of each joint was significantly associated with disability in each category. After adjusting for disease activity, age, and sex, shoulder abduction had the highest independent impact on disability in activity [cut-off: 139 degrees (OR: 5.26)], elbow flexion-extension in dressing [121 degrees (OR: 2.22)], wrist flexion-extension in reach [86 degrees (OR: 2.71)], hip flexion-extension in walking [126 degrees (OR: 3.42)], and knee flexion-extension in walking [134 degrees (OR: 2.97)]. Limited ROM of multiple joints was significantly associated with functional impairment in patients with long-standing RA. Motion in daily activity involves multiple joints, and at least two joints were independently involved in disability.

  13. Language Impairment in Cerebellar Ataxia

    NARCIS (Netherlands)

    van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

    Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

  14. Oceanography for the Visually Impaired

    Science.gov (United States)

    Fraser, Kate

    2008-01-01

    Amy Bower is a physical oceanographer and senior scientist at the Woods Hole Oceanographic Institution (WHOI) in Woods Hole, Massachusetts--she has also been legally blind for 14 years. Through her partnership with the Perkins School for the Blind in Watertown, Massachusetts, the oldest K-12 school for the visually impaired in the United States,…

  15. Parkinson's Disease and Cognitive Impairment.

    Science.gov (United States)

    Yang, Yang; Tang, Bei-Sha; Guo, Ji-Feng

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice.

  16. Targets and teamwork

    DEFF Research Database (Denmark)

    Skinner, Timothy C.; Lange, Karin S.; Hoey, Hilary

    2017-01-01

    with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. Conclusions: The diabetes care...

  17. Variation in radiotherapy target volume definition, dose to organs at risk and clinical target volumes using anatomic (computed tomography) versus combined anatomic and molecular imaging (positron emission tomography/computed tomography): intensity-modulated radiotherapy delivered using a tomotherapy Hi Art machine: final results of the VortigERN study.

    Science.gov (United States)

    Chatterjee, S; Frew, J; Mott, J; McCallum, H; Stevenson, P; Maxwell, R; Wilsdon, J; Kelly, C G

    2012-12-01

    Contrast-enhanced computed tomography (CECT) is the current standard for delineating tumours of the head and neck for radiotherapy. Although metabolic imaging with positron emission tomography (PET) has been used in recent years, the studies were non-confirmatory in establishing its routine role in radiotherapy planning in the modern era. This study explored the difference in gross tumour volume and clinical target volume definitions for the primary and nodal volumes when FDG PET/CT was used as compared with CECT in oropharyngeal cancer cases. Twenty patients with oropharyngeal cancers had a PET/CT scan in the treatment position after consent. Target volumes were defined on CECT scans by a consultant clinical oncologist who was blind to the PET scans. After obtaining inputs from a radiologist, another set of target volumes were outlined on the PET/CT data set. The gross and clinical target volumes as defined on the two data sets were then analysed. The hypothesis of more accurate target delineation, preventing geographical miss and comparative overlap volumes between CECT and PET/CT, was explored. The study also analysed the volumes of intersection and analysed whether there was any TNM stage migration when PET/CT was used as compared with CECT for planning. In 17 of 20 patients, the TNM stage was not altered when adding FDG PET information to CT. PET information prevented geographical miss in two patients and identified distant metastases in one case. PET/CT gross tumour volumes were smaller than CECT volumes (mean ± standard deviation: 25.16 cm(3) ± 35.8 versus 36.56 cm(3) ± 44.14; P standard deviation: CECT versus PET/CT 32.48 cm(3) ± 36.63 versus 32.21 cm(3) ± 37.09; P > 0.86) were not statistically different. Similarity and discordance coefficients were calculated and are reported. PET/CT as compared with CECT could provide more clinically relevant information and prevent geographical miss when used for radiotherapy planning for advanced oropharyngeal

  18. The Importance of Identifying Early Changes in Cardiac Structure and Function for the Prevention of Cognitive Impairment and Dementia.

    Science.gov (United States)

    Edwards, Jodi D

    2017-01-01

    Multiple cardiac pathologies have been shown to contribute to progressive cognitive decline and dementia in elderly populations, including left ventricular hypertrophy (LVH), a marker of prolonged exposure to hypertension. Although associations between chronic hypertension and cognitive function are thought to be mediated primarily by these end organ effects, there is increasing evidence that early changes in cardiac structure and function, such as LVH, may independently contribute to cognitive decline and impairment. In the current issue of the Journal of Alzheimer's Disease, Mahinrad and colleagues report important new findings on the association between LVH and cognitive function that are incremental to cardiovascular risk and co-morbidity, including hypertension. Emerging evidence that early changes in cardiac structure and function may independently contribute to cognitive decline in elderly populations has resulted in an increased interest in these preclinical substrates as potential treatment targets for the prevention of cognitive decline and in their putative contributions to the pathogenesis of dementia.

  19. Influence of visual impairment and hearing impairment on functional dependence status among people in Taiwan-An evaluation using the WHODAS 2.0 score.

    Science.gov (United States)

    Chang, Ko-Fang; Chang, Kwang-Hwa; Chi, Wen-Chou; Huang, Shih-Wei; Yen, Chia-Feng; Liao, Hua-Fang; Liou, Tsan-Hon; Chao, Pin-Zhir; Lin, I-Chan

    2018-04-01

    Visual impairment (VI) and hearing impairment (HI) are the two most common types of sensory disability encountered clinically. However, VI and HI result in different limitations in daily life. We assessed the level of functioning in patients with VI or HI based on the International Classification of Functioning, Disability, and Health. This nationwide, cross-sectional study included 312 people with VI and 540 people with HI. Each participant's degree of functioning and disability was evaluated using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The standardized WHODAS 2.0 scores ranged from 0 (least difficulty) to 100 (most difficulty). Patients with VI and those with HI had a mean (±standard error) 32-item WHODAS 2.0 score of 42.4 ± 2.9 and 27.1 ± 1.6, respectively. The degree of restriction was positively related to the level of VI. Specifically, the patients with VI and a WHODAS 2.0 score of 33.7-35.3 or higher were likely to experience barriers to accessing mobility products, communication products, and education products. Furthermore, patients with a score of 42.9 or higher might experience barriers to accessing ingestion products and living products. WHODAS 2.0 scores are strongly correlated with the severity of VI. Mild VI should be targeted for treatment and referral as early as possible. Compared with the patients with HI, the patients with VI more frequently experience barriers to accessing environmental factors. Copyright © 2017. Published by Elsevier Taiwan LLC.

  20. FREQUENCY OF HEARING IMPAIRMENT IN METAL INDUSTRY AND REPERCUSSION ON PROFESSIONAL ENABLING OF DEAF

    Directory of Open Access Journals (Sweden)

    Husnija Hasanbegović

    2011-04-01

    Full Text Available The survey has been done on sample of 1252 people. The target was to estimate damage of noise on professional rehabilitation of deaf population, which is mostly directed to professions in heavy industry, for professions in metal industry. Sample has been divided to 3 sub samples: 137 hearing people in metal industry; 106 hearing impaired adults with different professions and control group of 1000 hearing people. The results of survey point that work conditions contribute to hearing damage at employers in metal industry by comparison with hearing impairment of usual population. By comparative analysis of registered hearing impairments concerning age, statistically important difference in frequency of hearing impairment of two sub samples (t= 3.27, sing=.05. The relation between hearing impairment and years of working has been identifi ed at employers in heavy industry, (r=.37.

  1. Frequency of Hearing Impairment in Metal Industry and Repercussion on Professional Enabling of Deaf

    Directory of Open Access Journals (Sweden)

    Husnija Hasanbegovic

    2011-08-01

    Full Text Available The survey has been done on sample of 1252 people. The target was to estimate damage of noise on professional rehabilitation of deaf population, which is mostly directed to professions in heavy industry, for professions in metal industry. Sample has been divided to 3 sub samples: 137 hearing people in metal industry; 106 hearing impaired adults with different professions and control group of 1000 hearing people. The results of survey point that work conditions contribute to hearing damage at employers in metal industry by comparison with hearing impairment of usual population. By comparative analysis of registered hearing impairments concerning age, statistically important difference in frequency of hearing impairment of two sub samples (t= 3.27, sing=.05. The relation between hearing impairment and years of working has been identify ed at employers in heavy industry, (r=.37.

  2. A high-throughput approach to identify compounds that impair envelope integrity in Escherichia coli

    DEFF Research Database (Denmark)

    Baker, Kristin Renee; Jana, Bimal; Franzyk, Henrik

    2016-01-01

    . coli gene deletion mutants with impaired envelope integrity. As a proof of concept, a compound library comprising 36 peptides and 45 peptidomimetics was screened, leading to identification of two peptides that substantially increased envelope permeability. Compound 79 reduced significantly (from 8...... the discovery of antimicrobial helper drug candidates and targets that enhance the delivery of existing antibiotics by impairing envelope integrity in Gram-negative bacteria....

  3. Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

    Science.gov (United States)

    Sun, Miao-Kun

    2017-10-16

    As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Visuo-motor coordination deficits and motor impairments in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Rivka Inzelberg

    Full Text Available BACKGROUND: Visuo-motor coordination (VMC requires normal cognitive executive functionality, an ability to transform visual inputs into movement plans and motor-execution skills, all of which are known to be impaired in Parkinson's disease (PD. Not surprisingly, a VMC deficit in PD is well documented. Still, it is not known how this deficit relates to motor symptoms that are assessed routinely in the neurological clinic. Such relationship should reveal how particular motor dysfunctions combine with cognitive and sensory-motor impairments to produce a complex behavioral disability. METHODS AND FINDINGS: Thirty nine early/moderate PD patients were routinely evaluated, including motor Unified Parkinson's Disease Rating Scale (UPDRS based assessment, A VMC testing battery in which the subjects had to track a target moving on screen along 3 different paths, and to freely trace these paths followed. Detailed kinematic analysis of tracking/tracing performance was done. Statistical analysis of the correlations between measures depicting various aspects of VMC control and UPDRS items was performed. The VMC measures which correlated most strongly with clinical symptoms represent the ability to organize tracking movements and program their direction, rather than measures representing motor-execution skills of the hand. The strong correlations of these VMC measures with total UPDRS score were weakened when the UPDRS hand-motor part was considered specifically, and were insignificant in relation to tremor of the hand. In contrast, all correlations of VMC measures with the gait/posture part of the UPDRS were found to be strongest. CONCLUSIONS: Our apparently counterintuitive findings suggest that the VMC deficit pertains more strongly to a PD related change in cognitive-executive control, than to a reduction in motor capabilities. The recently demonstrated relationship between gait/posture impairment and a cognitive decline, as found in PD, concords with this

  5. Implementing SFAS No 121: Accounting for Impaired Assets.

    Science.gov (United States)

    Luecke, R W; Meeting, D T; Stotzer, W G

    1996-10-01

    In March 1995, FASB issued Statement of Financial Accounting Standards (SFAS) No. 121: "Accounting for the Impairment of Long-Lived Assets and for Long-Lived Assets to be Disposed Of." It establishes accounting standards for assets whose carrying costs have been overstated due to a variety of circumstances that have reduced the value of the assets. Healthcare financial managers should fully understand the statement's implications for their organizations.

  6. Beam splitting to improve target life in neutron generators

    International Nuclear Information System (INIS)

    Farrell, J.P.

    1976-01-01

    In a neutron generator in which a tritium-titanium target is bombarded by a deuterium ion beam, the target half-life is increased by separating the beam with a weak magnetic field to provide three separate beams of atomic, diatomic, and triatomic deuterium ions which all strike the target at different adjacent locations. Beam separation in this manner eliminates the problem of one type ion impairing the neutron generating efficiency of other type ions, thereby effecting more efficient utilization of the target material

  7. Molecular Targets for Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Mather, S.J.

    2009-01-01

    Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

  8. Clinical variables associated with leprosy reactions and persistence of physical impairment

    Directory of Open Access Journals (Sweden)

    Daniela Teles de Oliveira

    2013-10-01

    Full Text Available Introduction Leprosy is a chronic disease that affects skin and peripheral nerves. Disease complications include reactional episodes and physical impairment. One World Health Organization (WHO goal of leprosy programs is to decrease the number of grade 2 impairment diagnoses by 2015. This study aims to evaluate clinical factors associated with the occurrence of leprosy reactions and physical impairment in leprosy patients. Methods We conducted a retrospective study of data from medical records of patients followed in two important centers for the treatment of leprosy in Aracaju, Sergipe, Brazil, from 2005 to 2011. We used the chi-square test to analyze associations between the following categorical variables: gender, age, operational classification, clinical forms, leprosy reactions, corticosteroid treatment, and physical impairment at the diagnosis and after cure. Clinical variables associated with multibacillary leprosy and/or reactional episodes and the presence of any grade of physical impairment after cure were evaluated using the logistic regression model. Results We found that men were more affected by multibacillary forms, reactional episodes, and grade 2 physical impairment at diagnosis. Leprosy reactions were detected in a total of 40% of patients and all were treated with corticosteroids. However, physical impairment was observed in 29.8% of the patients analyzed at the end of the treatment and our multivariate analysis associated a low dose and short period of corticosteroid treatment with persistence of physical impairments. Conclusions Physical impairment should receive an increased attention before and after treatment, and adequate treatment should be emphasized.

  9. Cognitive impairment in Chinese neuromyelitis optica

    NARCIS (Netherlands)

    Zhang, N.; Li, Y.J.; Fu, Y.; Shao, J.H.; Luo, L.L.; Yang, L.; Shi, F.D.; Liu, Y.

    2015-01-01

    Background: Cognitive dysfunction is frequently seen in neuromyelitis optica (NMO). However, the features and influencing factors of cognitive impairment of Chinese NMO patients are unclear. Objective: To investigate the patterns of cognitive impairment in Chinese NMO patients, and correlate the

  10. Cerebral visual impairment in children.

    Science.gov (United States)

    Dutton, G N; Jacobson, L K

    2001-12-01

    Much of the brain is devoted to vision. Damage causes visual problems ranging from profound impairment, to cognitive visual problems only. A child with cerebral blindness may have intact perception of movement. The principal cognitive visual pathways comprise the dorsal and the ventral streams. The dorsal stream runs between the occipital lobes (which process incoming visual data), the posterior parietal lobes (which process the whole visual scene and give attention to component parts), the motor cortex (which facilitates movement through the visual scene) and the frontal cortex (which directs attention to chosen parts of the visual scene). The ventral stream runs between the occipital lobes and the temporal lobes (which enable recognition of people and objects, facilitate route finding and serve visual memory). Damage to these pathways disrupts these functions in a variety of combinations. This paper reviews cerebral visual impairment in children, the differential diagnosis and the management. Copyright 2002 Elsevier Science Ltd.

  11. Impaired sleep and allostatic load

    DEFF Research Database (Denmark)

    Clark, Alice Jessie; Dich, Nadya; Lange, Theis

    2014-01-01

    Objective: Understanding the mechanisms linking sleep impairment to morbidity and mortality is important for future prevention, but these mechanisms are far from elucidated. We aimed to determine the relation between impaired sleep, both in terms of duration and disturbed sleep, and allostatic load...... Biobank with comprehensive information on sleep duration, disturbed sleep, objective measures of an extensive range of biological risk markers, and physical conditions. Results: Long sleep (mean difference 0.23; 95% confidence interval, 0.13, 0.32) and disturbed sleep (0.14; 0.06, 0.22) were associated...... with higher AL as well as with high-risk levels of risk markers from the anthropometric, metabolic, and immune system. Sub-analyses suggested that the association between disturbed sleep and AL might be explained by underlying disorders. Whereas there was no association between short sleep and AL...

  12. Relevance theory and pragmatic impairment.

    Science.gov (United States)

    Leinonen, E; Kerbel, D

    1999-01-01

    This paper summarizes aspects of relevance theory that are useful for exploring impairment of pragmatic comprehension in children. It explores data from three children with pragmatic language difficulties within this framework. Relevance theory is seen to provide a means of explaining why, in a given context, a particular utterance is problematic. It thus enables one to move on from mere description of problematic behaviours towards their explanation. The theory provides a clearer delineation between the explicit and the implicit, and hence between semantics and pragmatics. This enables one to place certain difficulties more firmly within semantics and others within pragmatics. Relevance, and its maximization in communication, are squarely placed within human cognition, which suggests a close connection between pragmatic and cognitive (dis)functioning. Relevance theory thus emerges as a powerful tool in the exploration and understanding of pragmatic language difficulties in children and offers therapeutically valuable insight into the nature of interactions involving individuals with such impairments.

  13. Human target acquisition performance

    Science.gov (United States)

    Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

    2012-06-01

    The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

  14. Multilingualism and Specific Language Impairment

    OpenAIRE

    Engel de Abreu, Pascale

    2014-01-01

    Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? When should we be concerned about a multilingual child's language skills? What are the signs of Specific Language Impairment in a child who speaks more than one language? Developmental psychologist and Associate Professor in multilingual cognitive development at the University of Luxembourg Pascale Engel de Abreu will address these questions based on what...

  15. Monitoring brain potentials to guide neurorehabilitation of tracking impairments.

    Science.gov (United States)

    Yazmir, Boris; Reiner, Miriam

    2017-07-01

    Motor impairments come in different forms. One class of motor impairments, relates to accuracy of tracking a moving object, as, for instance, when chasing in an attempt to catch it. Here we look at neural signals associated with errors in tracking, and the implications for brain-computer-interfaces that target impairment-tailored rehabilitation. As a starting point, we characterized EEG signals evoked by tracking errors during continuous natural motion, in healthy participants. Participants played a virtual 3D, ecologically valid haptic tennis game, and had to track a moving tennis ball in order to hit and send the ball towards the opponent's court. Sudden changes in the motion of the tennis ball elicited error related potentials. These were characterized by a negative peak at 135 msec and two positive peaks at 211 and 336 msec. The negative peak had a parietal scalp distribution, and the positive had a centro-frontal distribution. sLORETA source estimation for the peaks suggested brain activity in the somatosensory, motor, visual and anterior cingulate cortex. Implications are double: changes in the error potential characteristics provide an assessment strategy for rehabilitation; and the identified error potential can be used in the Brain computer interface feedback loop for tailored rehabilitation. Taken together, these results provide a methodology of rehabilitation systems specifically tailored to the unique impairment.

  16. Wound Healing in Patients With Impaired Kidney Function.

    Science.gov (United States)

    Maroz, Natallia; Simman, Richard

    2013-04-01

    Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium-phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients.

  17. Targeting MTHFD2 in acute myeloid leukemia.

    Science.gov (United States)

    Pikman, Yana; Puissant, Alexandre; Alexe, Gabriela; Furman, Andrew; Chen, Liying M; Frumm, Stacey M; Ross, Linda; Fenouille, Nina; Bassil, Christopher F; Lewis, Caroline A; Ramos, Azucena; Gould, Joshua; Stone, Richard M; DeAngelo, Daniel J; Galinsky, Ilene; Clish, Clary B; Kung, Andrew L; Hemann, Michael T; Vander Heiden, Matthew G; Banerji, Versha; Stegmaier, Kimberly

    2016-06-27

    Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. © 2016 Pikman et al.

  18. Impairment testing of assets according to IFRS

    OpenAIRE

    Procházka, Michal

    2014-01-01

    The main object of this thesis is to show measurement of assets and its changes under International Financial Reporting Standards with closer focus on impairment testing according to IAS 36 - Impairment of Assets. The first part of the thesis introduces definition of assets and possible measurement bases used at first time recognition and reporting date. The main part deals with impairment testing of individual assets and cash-generating units. There is described when the impairment testing m...

  19. Vascular cognitive impairment in dementia.

    Science.gov (United States)

    Etherton-Beer, Christopher D

    2014-10-01

    Vascular risk factors and cerebrovascular disease are common causes of dementia. Shared risk factors for vascular dementia and Alzheimer's disease, as well as frequent coexistence of these pathologies in cognitively impaired older people, suggests convergence of the aetiology, prevention and management of the commonest dementias affecting older people. In light of this understanding, the cognitive impairment associated with cerebrovascular disease is an increasingly important and recognised area of the medicine of older people. Although the incidence of cerebrovascular events is declining in many populations, the overall burden associated with brain vascular disease will continue to increase associated with population ageing. A spectrum of cognitive disorders related to cerebrovascular disease is now recognised. Cerebrovascular disease in older people is associated with specific clinical and imaging findings. Although prevention remains the cornerstone of management, the diagnosis of brain vascular disease is important because of the potential to improve clinical outcomes through clear diagnosis, enhanced control of risk factors, lifestyle interventions and secondary prevention. Specific pharmacological intervention may also be indicated for some patients with cognitive impairment and cerebrovascular disease. However the evidence base to guide intervention remains relatively sparse. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Cognitive impairment in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Jing YUAN

    2017-07-01

    Full Text Available Parkinson's disease cognitive impairment (PD-CI is one of the major non-motor symtoms (NMS of PD, including Parkinson's disease with mild cognitive impairment (PD - MCI and Parkinson's disease dementia (PDD. Executive dysfunction is relatively prominent, but other cognitive domains as visuospatial ability, memory and language can also be affected. Main risk factors for PD-CI include male gender, advanced age, low education, severe motor symptoms, low baseline cognitive function and excessive daytime sleepiness (EDS. Lewy bodies are main pathological changes, and Alzheimer's disease (AD related pathological changes can also be seen. The application value of decreased α?synuclein (α-Syn and β-amyloid 1-42 (Aβ1-42 levels in cerebrospinal fluid (CSF as biomarkers remains controversial. There are few related research and no defined pathogenic genes currently. Both dopaminergic pathway and acetylcholinergic pathway are involved in the occurrence of PD - CI as demonstrated in PET studies. Cortical and subcortical atrophy are associated with PD - CI as observed in MRI studies. Olfactory dysfunction may be one of the predictors of cognitive impairment. PDD and dementia with Lewy bodies (DLB share common biological characteristics, therefore the differential diagnosis sometimes is difficult. Cholinesterase inhibitors (ChEIs and memantine help to improve clinical symptoms, but treatment decision should be made with individualization. Cognitive behavioral treatment (CBT has potential clinical value and should be investigated by more studies. DOI: 10.3969/j.issn.1672-6731.2017.06.004

  1. Communication Skills and Learning in Impaired Individuals

    Science.gov (United States)

    Eliöz, Murat

    2016-01-01

    The purpose of this study is to compare the communication skills of individuals with different disabilities with athletes and sedentary people and to examine their learning abilities which influence the development of communication. A total of 159 male subjects 31 sedentary, 30 visually impaired, 27 hearing impaired, 40 physically impaired and 31…

  2. Evacuation characteristics of visually impaired people

    DEFF Research Database (Denmark)

    Sørensen, Janne Gress; Dederichs, Anne

    2015-01-01

    Evacuation characteristics for blind and visually impaired people are presented in the current study. The study was carried out in 2011 and engaged 40 participants in the age from 10 to 69 years. The participants had impairments for all of the four Danish categories for visual impairments (A...

  3. Social Cognition in Children with Visual Impairments.

    Science.gov (United States)

    Pring, Linda; Dewart, Hazel; Brockbank, Margaret

    1998-01-01

    Comparison of 16 children (ages 9 to 12) with visual impairment to 16 sighted children found visually impaired children had a poorer understanding than did sighted children of characters in stories, as shown by fewer correct justifications based on mental states. Some subgroup patterns concerning congenital impairments and cognitive style were…

  4. Inferential Functioning in Visually Impaired Children

    Science.gov (United States)

    Puche-Navarro, Rebeca; Millan, Rafael

    2007-01-01

    The current study explores the inferential abilities of visually impaired children in a task presented in two formats, manipulative and verbal. The results showed that in the group of visually impaired children, just as with children with normal sight, there was a wide range of inference types. It was found that the visually impaired children…

  5. Evaluating the Visually Impaired: Neuropsychological Techniques.

    Science.gov (United States)

    Price, J. R.; And Others

    1987-01-01

    Assessment of nonvisual neuropsychological impairments in visually impaired persons can be achieved through modification of existing intelligence, memory, sensory-motor, personality, language, and achievement tests so that they do not require vision or penalize visually impaired persons. The Halstead-Reitan and Luria-Nebraska neuropsychological…

  6. Visual impairment, but not hearing impairment, is independently associated with lower subjective well-being among individuals over 95 years of age: A population-based study.

    Science.gov (United States)

    Liu, Zuyun; Wu, Di; Huang, Jiapin; Qian, Degui; Chen, Fei; Xu, Jun; Li, Shilin; Jin, Li; Wang, Xiaofeng

    2016-01-01

    Sensory impairment affects an increasing number of elderly adults, with a negative psychological impact. Our objective was to examine the associations of visual and hearing impairment with subjective well-being (SWB), an important psychological concept defined by life satisfaction [LS], positive affect [PA], negative affect [NA], and affect balance [AB] among long-lived individuals (LLIs) over 95 years of age. Data on 442 LLIs from the Rugao longevity cohort, a population-based study in Rugao, China, were analyzed. Graded classifications of visual and hearing impairment (none, mild, moderate, and severe) were constructed from self-reported items. Bivariate correlation and multiple regression analysis were performed to test the associations. Approximately 66.1% and 87.3% of the subjects reported varying degrees of visual and hearing impairment. Following the degree of vision impairment, LS, PA, and AB decreased linearly, whereas NA increased linearly (all p for trendimpairment with LS, NA, and AB, while diminished, still existed. Visual impairment, but not hearing impairment, was independently associated with low SWB among LLIs, and functional ability may play a mediating role in the observed relationship. The findings indicate that rehabilitation targeted for those with reduced vision and functioning in long-lived populations may be important for promoting well-being and quality of life. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Radiation during deep inspiration allows loco-regional treatment of left breast and axillary-, supraclavicular- and internal mammary lymph nodes without compromising target coverage or dose restrictions to organs at risk.

    Science.gov (United States)

    Hjelstuen, Mari H B; Mjaaland, Ingvil; Vikström, Johan; Dybvik, Kjell Ivar

    2012-03-01

    Loco-regional radiotherapy of left-sided breast cancer represents a treatment planning challenge when the internal mammary chain (IMC) lymph nodes are included in the target volume. This treatment planning study evaluates the reduction in cardiopulmonary doses when radiation is given during deep inspiration breath-hold (DIBH). This was achieved without compromising dose coverage to the planning target volume (PTV). Seventeen patients with early breast cancer, referred for adjuvant radiotherapy, were included. For each patient two computed tomography (CT)-scans were acquired; the first during free breathing (FB) and the second during DIBH. The scans were monitored by the Varian RPM respiratory gating system. Audio-visual guidance was used. The treatment planning of the two CT studies was performed focusing on good coverage (V95% > 98%) of the PTV. Doses to the heart, left anterior descending (LAD) coronary artery, lungs and contralateral breast were assessed. With equal PTV coverage, average mean heart dose was reduced from 6.2 Gy to 3.1 Gy in DIBH plans as compared to FB. Average volume receiving 25 Gy or more (V25Gy) was reduced from 6.7% to 1.2%, and the number of patients with V25Gy > 5% was reduced from 8 to 1 utilizing DIBH. The average mean dose to the LAD coronary artery was reduced from 25.0 Gy to 10.9 Gy. The average ipsilateral lung volume receiving 20 Gy or more (V20Gy) was reduced from 44.5% to 32.7% with DIBH. In 11 of the DIBH plans V20Gy was lower than 35%, in accordance with national guidelines, while none of the FB plans fulfilled this recommendation. Respiratory gated radiotherapy during DIBH is a suitable technique for loco-regional breast irradiation even when IMC lymph nodes are included in the PTV. Cardiopulmonary doses are considerably decreased for all dose levels without compromising the dose coverage to PTV.

  8. Targeted therapies for cancer

    Science.gov (United States)

    ... Kummar S, Murgo AJ, Tomaszewski JE, Doroshow JH. Therapeutic targeting of cancer cells: era of molecularly targeted agents. ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  9. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590...

  10. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590 spectrophotometer

  11. Effective and Efficient Stand Magnifier Use in Visually Impaired Children.

    Science.gov (United States)

    Liebrand-Schurink, Joyce; Cox, Ralf F A; van Rens, Ger H M B; Cillessen, Antonius H N; Meulenbroek, Ruud G J; Boonstra, Frouke N

    2016-01-01

    The main objective of this study was to analyze the effectiveness and efficiency of magnifier use in children with visual impairment who did not use a low vision aid earlier, in an ecologically valid goal-directed perceptuomotor task. Participants were twenty-nine 4- to 8-year-old children with visual impairment and 47 age-matched children with normal vision. After seeing a first symbol (an Lea Hyvärinen [LH] symbol), children were instructed to (1) move the stand magnifier as quickly as possible toward a small target symbol (another LH symbol that could only be seen by using the magnifier), (2) compare the two symbols, and (3) move the magnifier to one of two response areas to indicate whether the two symbols were identical. Performance was measured in terms of accuracy, response time, identification time, and movement time. Viewing distance, as well as hand and eye dominance while using the magnifier was assessed. There were no significant differences between the two groups in accuracy, reaction time, and movement time. Contrary to the prediction, children with visual impairment required less time to identify small symbols than children with normal vision. Both within-subject and between-subject variability in viewing distance were smaller in the visually impaired group than in the normally sighted group. In the visually impaired group, a larger viewing distance was associated with shorter identification time, which in turn was associated with higher accuracy. In the normally sighted group, a faster movement with the magnifier and a faster identification were associated with increasing age. The findings indicate that children with visual impairment can use the stand magnifier adequately and efficiently. The normally sighted children show an age-related development in movement time and identification time and show more variability in viewing distance, which is not found in visually impaired children. Visually impaired children seem to choose a standard but less

  12. Effective and Efficient Stand Magnifier Use in Visually Impaired Children

    Science.gov (United States)

    Liebrand-Schurink, Joyce; Cox, Ralf F. A.; van Rens, Ger H. M. B.; Cillessen, Antonius H. N.; Meulenbroek, Ruud G. J.; Boonstra, Frouke N.

    2016-01-01

    Purpose: The main objective of this study was to analyze the effectiveness and efficiency of magnifier use in children with visual impairment who did not use a low vision aid earlier, in an ecologically valid goal-directed perceptuomotor task. Methods: Participants were twenty-nine 4- to 8-year-old children with visual impairment and 47 age-matched children with normal vision. After seeing a first symbol (an Lea Hyvärinen [LH] symbol), children were instructed to (1) move the stand magnifier as quickly as possible toward a small target symbol (another LH symbol that could only be seen by using the magnifier), (2) compare the two symbols, and (3) move the magnifier to one of two response areas to indicate whether the two symbols were identical. Performance was measured in terms of accuracy, response time, identification time, and movement time. Viewing distance, as well as hand and eye dominance while using the magnifier was assessed. Results: There were no significant differences between the two groups in accuracy, reaction time, and movement time. Contrary to the prediction, children with visual impairment required less time to identify small symbols than children with normal vision. Both within-subject and between-subject variability in viewing distance were smaller in the visually impaired group than in the normally sighted group. In the visually impaired group, a larger viewing distance was associated with shorter identification time, which in turn was associated with higher accuracy. In the normally sighted group, a faster movement with the magnifier and a faster identification were associated with increasing age. Conclusion: The findings indicate that children with visual impairment can use the stand magnifier adequately and efficiently. The normally sighted children show an age-related development in movement time and identification time and show more variability in viewing distance, which is not found in visually impaired children. Visually impaired

  13. Cognitive approach to assessing pragmatic language comprehension in children with specific language impairment.

    Science.gov (United States)

    Ryder, Nuala; Leinonen, Eeva; Schulz, Joerg

    2008-01-01

    Pragmatic language impairment in children with specific language impairment has proved difficult to assess, and the nature of their abilities to comprehend pragmatic meaning has not been fully investigated. To develop both a cognitive approach to pragmatic language assessment based on Relevance Theory and an assessment tool for identifying a group of children with pragmatic language impairment from within an specific language impairment group. The authors focused on Relevance Theory's view of the role of context in pragmatic language comprehension using questions of increasing pragmatic complexity in different verbal contexts (scenarios with and without pictures and a story with supporting pictures). The performances of the children with and without pragmatic impairment on the most pragmatically demanding Implicature questions were examined. This study included 99 children: 27 with specific language impairment (including nine pragmatically impaired children) and two groups of typically developing children (32 children aged 5-6 years and 40 children aged 7-11 years). The specific language impairment group performed similarly to their peers when utilizing context in inferring referents, inferring semantic meaning, and generating Implicatures, only when the answer was provided by pictorial context. Both the children with specific language impairment and the 5-6 year olds were not yet competent at utilizing verbal context when answering the most pragmatically demanding questions (targeting Implicature). On these questions the children with pragmatic language impairment performed significantly poorer than the rest of the specific language impairment group and performance scores on Implicature questions were found to identify accurately the children with pragmatic language impairment from the rest of the specific language impairment group (sensitivity = 89%). Children's ability to infer and integrate information in the comprehension of pragmatic meaning was found to be

  14. Mitochondria Targeted Protein-Ruthenium Photosensitizer for Efficient Photodynamic Applications

    OpenAIRE

    Chakrabortty, Sabyasachi; Agrawalla, Bikram Keshari; Stumper, Anne; Vegi, Naidu M; Fischer, Stephan; Reichardt, Christian; K?gler, Michael; Dietzek, Benjamin; Feuring-Buske, Michaela; Buske, Christian; Rau, Sven; Weil, Tanja

    2017-01-01

    Organelle-targeted photosensitization represents a promising approach in photodynamic therapy where the design of the active photosensitizer (PS) is very crucial. In this work, we developed a macromolecular PS with multiple copies of mitochondria-targeting groups and ruthenium complexes that displays highest phototoxicity toward several cancerous cell lines. In particular, enhanced anticancer activity was demonstrated in acute myeloid leukemia cell lines, where significant impairment of proli...

  15. Low sustainability, poor governance, and other challenges encountered by grassroots non-governmental organizations targeting HIV prevention for men who have sex with men in China - a nation-wide study.

    Science.gov (United States)

    Lau, Joseph T F; Wang, Zixin; Kim, Yoona; Li, Jinghua; Gu, Jing; Mo, Phoenix K H; Wang, Xiaodong

    2017-12-01

    Grassroots non-governmental organizations (NGOs) played pivotal roles in HIV prevention among men who have sex with men (MSM) in China. Their governance and sustainability issues were under-studied. This nation-wide study surveyed leaders of 202 of the HIV related NGOs in China.58.4% of the leaders believed that their NGO would last for ≤5 years; which was negatively associated with perceived good relationship with CDC. 65.3% mentioned ≥3 non-sustainability issues; associated factors included perceived inadequacies in prevention skills, management skills, policy support, technical support, operational support, and CDC's support; a reverse association was found for frequent collaboration with organizations in China. 30.6% of the leaders mentioned ≥7 governance issues; a stepwise model found a positive association with having no office and negative associations with number of full-time staff and core volunteers. These problems would severely limit the effectiveness of HIV prevention among MSM. Related improvements and support are warranted.

  16. TARGET COSTING FUNCTIONS

    OpenAIRE

    OFILEANU Dimi

    2015-01-01

    This article aims to highlight the concept of Target Costing. Based on the characteristics of Target Costing, identified in specialized literature, the article presents its main advantages and disadvantages. Also, a comparison is being made between Target Cost and Traditional Cost (in its traditional form, the cost represents an independent variable on the basis of which the sell price is established; and in the Target Cost form the cost represents a dependent variable which is determined on ...

  17. Targeting outcomes redux

    OpenAIRE

    Coady, David P.; Grosh, Margaret; Hoddinott, John

    2002-01-01

    "...There are sharply divergent views as to how much narrowly targeted interventions actually benefit the poor. These result from differing assessments of three issues: whether better targeting outcomes are likely to be achieved, whether such methods are cost-effective, and whether the living standards of the poor are improved by such targeted interventions. This paper focuses on the first issue. Using a newly constructed database of targeted interventions, it addresses three questions: (1) W...

  18. Graphite targets at LAMPF

    International Nuclear Information System (INIS)

    Brown, R.D.; Grisham, D.L.

    1983-01-01

    Rotating polycrystalline and stationary pyrolytic graphite target designs for the LAMPF experimental area are described. Examples of finite element calculations of temperatures and stresses are presented. Some results of a metallographic investigation of irradiated pyrolytic graphite target plates are included, together with a brief description of high temperature bearings for the rotating targets

  19. Manneristic behaviors of visually impaired children.

    Science.gov (United States)

    Molloy, Alysha; Rowe, Fiona J

    2011-09-01

    To review the literature on visual impairment in children in order to determine which manneristic behaviors are associated with visual impairment, and to establish why these behaviors occur and whether severity of visual impairment influences these behaviors. A literature search utilizing PubMed, OVID, Google Scholar, and Web of Knowledge databases was performed. The University of Liverpool ( www.liv.ac.uk/orthoptics/research ) and local library facilities were also searched. The main manneristic or stereotypic behaviors associated with visual impairment are eye-manipulatory behaviors, such as eye poking and rocking. The degree of visual impairment influences the type of behavior exhibited by visually impaired children. Totally blind children are more likely to adopt body and head movements whereas sight-impaired children tend to adopt eye-manipulatory behaviors and rocking. The mannerisms exhibited most frequently are those that provide a specific stimulation to the child. Theories to explain these behaviors include behavioral, developmental, functional, and neurobiological approaches. Although the precise etiology of these behaviors is unknown, it is recognized that each of the theories is useful in providing some explanation of why certain behaviors may occur. The age at which the frequency of these behaviors decreases is associated with the child's increasing development, thus those visually impaired children with additional disabilities, whose development is impaired, are at an increased risk of developing and maintaining these behaviors. Certain manneristic behaviors of the visually impaired child may also help indicate the cause of visual impairment. There is a wide range of manneristic behaviors exhibited by visually impaired children. Some of these behaviors appear to be particularly associated with certain causes of visual impairment or severity of visual impairment, thus they may supply the practitioner with useful information. Further research into the

  20. Predicting the Reliability of Drug-target Interaction Predictions with Maximum Coverage of Target Space.

    Science.gov (United States)

    Peón, Antonio; Naulaerts, Stefan; Ballester, Pedro J

    2017-06-19

    Many computational methods to predict the macromolecular targets of small organic molecules have been presented to date. Despite progress, target prediction methods still have important limitations. For example, the most accurate methods implicitly restrict their predictions to a relatively small number of targets, are not systematically validated on drugs (whose targets are harder to predict than those of non-drug molecules) and often lack a reliability score associated with each predicted target. Here we present a systematic validation of ligand-centric target prediction methods on a set of clinical drugs. These methods exploit a knowledge-base covering 887,435 known ligand-target associations between 504,755 molecules and 4,167 targets. Based on this dataset, we provide a new estimate of the polypharmacology of drugs, which on average have 11.5 targets below IC 50 10 µM. The average performance achieved across clinical drugs is remarkable (0.348 precision and 0.423 recall, with large drug-dependent variability), especially given the unusually large coverage of the target space. Furthermore, we show how a sparse ligand-target bioactivity matrix to retrospectively validate target prediction methods could underestimate prospective performance. Lastly, we present and validate a first-in-kind score capable of accurately predicting the reliability of target predictions.

  1. Impairing somatosensory working memory using rTMS.

    Science.gov (United States)

    Auksztulewicz, Ryszard; Spitzer, Bernhard; Goltz, Dominique; Blankenburg, Felix

    2011-09-01

    Numerous studies in animals and humans have related central aspects of somatosensory working memory function to neural activity in the inferior frontal gyrus (IFG). However, as previous studies have almost exclusively used correlational analyses, the question whether sustained neural activity in the IFG is causally involved in successful maintenance of somatosensory information remains unanswered. We used an online repetitive transcranial magnetic stimulation (rTMS) protocol to disrupt neuronal activity in the IFG while participants were maintaining tactile information throughout the delay for later comparison against a probe stimulus. rTMS impaired participants' performance in the working memory task, but not in a physically matched perceptual control task. Targeting the IFG in either hemisphere led to comparable working memory impairment. Our results show that the neural activity in the IFG plays a causal role in successful maintenance of somatosensory information. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  2. Mild cognitive impairment affects motor control and skill learning.

    Science.gov (United States)

    Wu, Qiaofeng; Chan, John S Y; Yan, Jin H

    2016-02-01

    Mild cognitive impairment (MCI) is a transitional phase between normal cognitive aging and dementia. As the world population is aging rapidly, more MCI patients will be identified, posing significant problems to society. Normal aging is associated with cognitive and motor decline, and MCI brings additional impairments. Compared to healthy older adults, MCI patients show poorer motor control in a variety of tasks. Efficient motor control and skill learning are essential for occupational and leisure purposes; degradation of motor behaviors in MCI patients often adversely affects their health and quality of life. In this article, we first define MCI and describe its pathology and neural correlates. After this, we review cognitive changes and motor control and skill learning in normal aging. This section is followed by a discussion of MCI-related degradation of motor behaviors. Finally, we propose that multicomponent interventions targeting both cognitive and motor domains can improve MCI patients' motor functions. Future research directions are also raised.

  3. Dual language intervention for bilinguals at risk for language impairment.

    Science.gov (United States)

    Lugo-Neris, Mirza J; Bedore, Lisa M; Peña, Elizabeth D

    2015-05-01

    Selecting the initial language of intervention for bilingual children at risk for language impairment is challenging for clinicians, as both the home and academic languages are important for children's successful communication. In this project, six Spanish-English bilingual first graders at risk for language impairment participated in an 8-week intervention program targeting vocabulary, morphosyntax, narrative, and literacy skills in both Spanish and English. Children completed 24 small-group sessions (three times a week). One group received Spanish intervention first, then English, and another group received English first, then Spanish. The systematic use of both languages in intervention resulted in overall gains in vocabulary and narrative skills in this short-term intervention. Language condition groups differed in performance on oral narratives and semantics. Clinical recommendations for selecting the initial language of intervention are discussed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Does remembering emotional items impair recall of same-emotion items?

    Science.gov (United States)

    Sison, Jo Ann G; Mather, Mara

    2007-04-01

    In the part-set cuing effect, cuing a subset of previously studied items impairs recall of the remaining noncued items. This experiment reveals that cuing participants with previously-studied emotional pictures (e.g., fear-evoking pictures of people) can impair recall of pictures involving the same emotion but different content (e.g., fear-evoking pictures of animals). This indicates that new events can be organized in memory using emotion as a grouping function to create associations. However, whether new information is organized in memory along emotional or nonemotional lines appears to be a flexible process that depends on people's current focus. Mentioning in the instructions that the pictures were either amusement- or fear-related led to memory impairment for pictures with the same emotion as cued pictures, whereas mentioning that the pictures depicted either animals or people led to memory impairment for pictures with the same type of actor.

  5. Vision Impairment and Ocular Morbidity in a Refugee Population in Malawi.

    Science.gov (United States)

    Kaphle, Dinesh; Gyawali, Rajendra; Kandel, Himal; Reading, Angela; Msosa, Joseph Matiya

    2016-02-01

    To provide screening services and obtain information on the eye health status and distribution of visual impairments in a refugee population of the sole refugee camp in Malawi. A general eye screening at Dzaleka refugee settlement camp was organized in November 2012. Final-year optometry students conducted detailed optometry examinations, including visual acuity (VA) assessment for near and distance, retinoscopy, and subjective refraction in cases with distance VA less than 6/12 or near VA less than N8, anterior and posterior segment evaluation. Their findings were then verified by an optometrist. The World Health Organization definition of vision impairment was followed, and the cause of vision impairment was determined at the end of each examination. Where possible, participants requiring refractive correction were provided spectacles free of cost. Of a total 635 participants examined, around one-half were male with 61% in the 16 to 49 years age group. The overall prevalence of presenting blindness, severe vision impairment, and vision impairment were 1.3% (95% confidence interval [95% CI], 0.5 to 2.4), 0.5% (95% CI, 0.0 to 1.1), and 3.6% (95% CI, 2.3 to 5.2), respectively. Overall vision impairment (VA vision impairment, and vision impairment were cataracts, refractive errors, and corneal opacities, respectively; and more than 90% of the overall vision impairment was avoidable. Refractive errors and presbyopia were the most common morbidity, present in more than two-thirds of the participants examined. Only 5% of all the participants ever had a previous eye examination. The prevalence and causes of blindness and vision impairment in a refugee population are comparable with those of the general population. Lack of basic eye care services in the health center for refugees is a major concern. The health care facility in the settlement camp needs to be upgraded to provide comprehensive eye care including refractive care services.

  6. Targeted Treatments in Autism and Fragile X Syndrome

    Science.gov (United States)

    Gurkan, C. Kagan; Hagerman, Randi J.

    2012-01-01

    Autism is a neurodevelopmental disorder consisting of a constellation of symptoms that sometimes occur as part of a complex disorder characterized by impairments in social interaction, communication and behavioral domains. It is a highly disabling disorder and there is a need for treatment targeting the core symptoms. Although autism is accepted…

  7. Postural control of elderly: moving to predictable and unpredictable targets.

    NARCIS (Netherlands)

    Jongman, Vera; Lamoth, Claudine J C; van Keeken, Helco; Caljouw, Simone R

    2012-01-01

    Impaired postural control with muscle weakness is an important predictor of falls within the elderly population.Particular daily activities that require weight shifting in order to be able to reach a specific target (a cup on a table) require continuous adjustments to keep the body's center of mass

  8. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug...... to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...... delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....

  9. Development of distributed target

    CERN Document Server

    Yu Hai Jun; Li Qin; Zhou Fu Xin; Shi Jin Shui; Ma Bing; Chen Nan; Jing Xiao Bing

    2002-01-01

    Linear introduction accelerator is expected to generate small diameter X-ray spots with high intensity. The interaction of the electron beam with plasmas generated at the X-ray converter will make the spot on target increase with time and debase the X-ray dose and the imaging resolving power. A distributed target is developed which has about 24 pieces of thin 0.05 mm tantalum films distributed over 1 cm. due to the structure adoption, the distributed target material over a large volume decreases the energy deposition per unit volume and hence reduces the temperature of target surface, then reduces the initial plasma formalizing and its expansion velocity. The comparison and analysis with two kinds of target structures are presented using numerical calculation and experiments, the results show the X-ray dose and normalized angle distribution of the two is basically the same, while the surface of the distributed target is not destroyed like the previous block target

  10. Myocardial fibroblast-matrix interactions and potential therapeutic targets.

    Science.gov (United States)

    Goldsmith, Edie C; Bradshaw, Amy D; Zile, Michael R; Spinale, Francis G

    2014-05-01

    The cardiac extracellular matrix (ECM) is a dynamic structure, adapting to physiological and pathological stresses placed on the myocardium. Deposition and organization of the matrix fall under the purview of cardiac fibroblasts. While often overlooked compared to myocytes, fibroblasts play a critical role in maintaining ECM homeostasis under normal conditions and in response to pathological stimuli assume an activated, myofibroblast phenotype associated with excessive collagen accumulation contributing to impaired cardiac function. Complete appreciation of fibroblast function is hampered by the lack of fibroblast-specific reagents and the heterogeneity of fibroblast precursors. This is further complicated by our ability to dissect the role of myofibroblasts versus fibroblasts in myocardial in remodeling. This review highlights critical points in the regulation of collagen deposition by fibroblasts, the current panel of molecular tools used to identify fibroblasts and the role of fibroblast-matrix interactions in fibroblast function and differentiation into the myofibroblast phenotype. The clinical potential of exploiting differences between fibroblasts and myofibroblasts and using them to target specific fibroblast populations is also discussed. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium." Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Cognitive Impairment in Infratentorial Strokes

    Directory of Open Access Journals (Sweden)

    Melek Kandemir

    2009-12-01

    Full Text Available OBJECTIVE: Beginning in the mid-1980s, with anatomical, behavioral, and neuropsychological evidence, it was suggested that the role of the cerebellum extends beyond a purely motor domain. A series of articles were published reviewing the potential role of the cerebellum in cognition. Both of these functions are supported by connections of dentate nucleus and frontal cortex through the thalamus. The cognitive profile of isolated subtentorial and cerebellar infarcts is related to the involved frontal circuit (especially executive functions. In this study, we aimed to demonstrate the cognitive profile of cerebellar and subtentorial infarcts. METHODS: Nineteen patients with infratentorial infarcts and 19 neurologically healthy individuals as a control group were included in this study. Neuropsychometric test battery was employed in both of the groups. RESULTS: Age, sex, education, clinical syndrome, and localization had no effect on the cognitive test performances. Performance on the California Verbal Learning Test, a verbal memory test, was worse in the patient group. Patients had difficulties in recognizing the items of the Rey-Osterrieth Complex Figure Test, and spent significantly more time to complete the trail making test part B. The patient group also demonstrated lower performance level in the verbal fluency test when compared to the control group. CONCLUSION: The cognitive impairment pattern of the verbal and visual memory tests and impairment determined on the verbal fluency test and the trail making tests may imply frontal impairment. Our results support the knowledge that cerebellar or brainstem strokes cause mild frontal type cognitive syndrome by damaging cerebello-ponto-thalamo-cortical pathways

  12. Emotional symptoms and their contribution to functional impairment in adults with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Mörstedt, Beatrice; Corbisiero, Salvatore; Bitto, Hannes; Stieglitz, Rolf-Dieter

    2016-03-01

    Attention-deficit/hyperactivity disorder (ADHD) is a severe neurodevelopmental disorder beginning in childhood and consisting of the core symptoms of inattention, hyperactivity, and impulsivity. The disorder is often accompanied by functional impairment in daily life. Research showed that severe impairment cannot be fully explained by the core symptoms of ADHD. Accordingly, emotional symptoms in ADHD and their influence on functional impairment have increasingly become the focus of research in recent years. The aim of the current study was to investigate the relationship between ADHD core symptoms, emotional symptoms, and functional impairment. We assumed that emotional symptoms might form part of adult ADHD and that the connection between ADHD core symptoms and functional impairment may be partly mediated by emotional symptoms. Data of 176 participants from an ADHD Special Consultations Unit were included. Of these participants, 146 were diagnosed with ADHD, while 30 received no such diagnosis. We developed a structural equation model which included core symptoms, emotional symptoms, and four domains of daily impairment (family life, social life, work, and organization). As predicted, results indicate that emotional symptoms are directly linked to adult ADHD and bear a strong negative influence on different domains of daily life. The results of different analyses showed a mediation of the relationship between ADHD core symptoms and impairment through emotional symptoms: While the connection between inattention and work and organization was partly mediated, the connections between impulsivity and family life and between inattention and social life were shown to be fully mediated through emotional symptoms.

  13. Impaired glucose tolerance in sleep disorders.

    Directory of Open Access Journals (Sweden)

    Marietta Keckeis

    Full Text Available BACKGROUND: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders. METHODOLOGY/PRINCIPAL FINDINGS: We performed oral glucose tolerance tests (OGTT and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25, restless legs syndrome (RLS, N = 18 or primary insomnia (N = 21, and in healthy controls (N = 33. Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9 and RLS (OR: 4.7 patients, but not in primary insomnia patients (OR: 1.6. In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05 and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05, respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases.

  14. Amusia and protolanguage impairments in schizophrenia.

    Science.gov (United States)

    Kantrowitz, J T; Scaramello, N; Jakubovitz, A; Lehrfeld, J M; Laukka, P; Elfenbein, H A; Silipo, G; Javitt, D C

    2014-10-01

    Both language and music are thought to have evolved from a musical protolanguage that communicated social information, including emotion. Individuals with perceptual music disorders (amusia) show deficits in auditory emotion recognition (AER). Although auditory perceptual deficits have been studied in schizophrenia, their relationship with musical/protolinguistic competence has not previously been assessed. Musical ability was assessed in 31 schizophrenia/schizo-affective patients and 44 healthy controls using the Montreal Battery for Evaluation of Amusia (MBEA). AER was assessed using a novel battery in which actors provided portrayals of five separate emotions. The Disorganization factor of the Positive and Negative Syndrome Scale (PANSS) was used as a proxy for language/thought disorder and the MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognition. Highly significant deficits were seen between patients and controls across auditory tasks (p amusia and intact music-perceiving groups, which remained significant after controlling for group status and education. Correlations with AER were specific to the melody domain, and correlations between protolanguage (melody domain) and language were independent of overall cognition. This is the first study to document a specific relationship between amusia, AER and thought disorder, suggesting a shared linguistic/protolinguistic impairment. Once amusia was considered, other cognitive factors were no longer significant predictors of AER, suggesting that musical ability in general and melodic discrimination ability in particular may be crucial targets for treatment development and cognitive remediation in schizophrenia.

  15. REM Sleep Behavior Disorder and Cognitive Impairment in Parkinson's Disease.

    Science.gov (United States)

    Jozwiak, Natalia; Postuma, Ronald B; Montplaisir, Jacques; Latreille, Véronique; Panisset, Michel; Chouinard, Sylvain; Bourgouin, Pierre-Alexandre; Gagnon, Jean-François

    2017-08-01

    REM sleep behavior disorder (RBD) is a parasomnia affecting 33% to 46% of patients with Parkinson's disease (PD). The existence of a unique and specific impaired cognitive profile in PD patients with RBD is still controversial. We extensively assessed cognitive functions to identify whether RBD is associated with more severe cognitive deficits in nondemented patients with PD. One hundred sixty-two participants, including 53 PD patients with RBD, 40 PD patients without RBD, and 69 healthy subjects, underwent polysomnography, a neurological assessment and an extensive neuropsychological exam to assess attention, executive functions, episodic learning and memory, visuospatial abilities, and language. PD patients with RBD had poorer and clinically impaired performance in several cognitive tests compared to PD patients without RBD and healthy subjects. These two latter groups were similar on all cognitive measures. Mild cognitive impairment (MCI) diagnosis frequency was almost threefold higher in PD patients with RBD compared to PD patients without RBD (66% vs. 23%, p < .001). Moreover, subjective cognitive decline was reported in 89% of PD patients with RBD compared to 58% of PD patients without RBD (p = .024). RBD in PD is associated with a more impaired cognitive profile and higher MCI diagnosis frequency, suggesting more severe and widespread neurodegeneration. This patient subgroup and their caregivers should receive targeted medical attention to better detect and monitor impairment and to enable the development of management interventions for cognitive decline and its consequences. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  16. Impaired Follistatin Secretion in Cirrhosis

    DEFF Research Database (Denmark)

    Rinnov, Anders Rasmussen; Plomgaard, Peter; Pedersen, Bente Klarlund

    2016-01-01

    compared to healthy control participants. DESIGN, SETTING, AND PARTICIPANTS: To experimentally increase the glucagon-insulin ratio (mimicking the hormonal effect of exercise), we infused glucagon/somatostatin (to inhibit insulin secretion) and compared the acute follistatin increase in eight male cirrhosis...... controls (27.6 ± 3.8 vs 34.5 ± 2.9%, respectively; P = .001). CONCLUSIONS: Patients with cirrhosis show impaired capacity to acutely secrete follistatin. The decrease in acute follistatin release may contribute to the loss of muscle mass in liver cirrhosis....

  17. Intermittent claudication: new targets for drug development.

    Science.gov (United States)

    Brass, Eric P

    2013-07-01

    Peripheral artery disease (PAD) is the result of extensive atherosclerosis in the arterial supply to the lower extremities. PAD is associated with increased systemic cardiovascular morbidity and mortality as well as substantial disability due to walking impairment. Claudication is the classic symptom of leg pain with walking that is relieved by rest, but patients with PAD without typical claudication also have a walking limitation. Treatment of the patient with PAD is directed towards reducing cardiovascular risk and improving exercise capacity. The pathophysiology of the physical impairment is complex as changes in the muscle distal to the arterial stenoses contribute to the limitations. Current treatment options to improve exercise performance have limitations emphasizing the need for new pharmacotherapies for this highly prevalent condition. The multifactorial contributors to the exercise impairment in PAD suggest potential targets for novel drug therapies. Advances in understanding angiogenesis make pharmacologic revascularization possible. However, ensuring that new blood vessels develop in a distribution relevant to the clinical impairment remains a challenge. Skeletal muscle metabolism and its regulation are altered in patients with PAD and strategies to improve the efficient oxidation of fuel substrates may improve muscle function. PAD is associated with increased oxidative stress which may result in injury to the muscle microvasculature and myocyte. Minimizing this oxidative stress by enhancing cellular defense mechanisms, administration of anti-inflammatory agents or by providing antioxidants, could prevent oxidative injury. Given the central role of atherosclerosis in the flow limitation, therapies to induce regression of atherosclerotic lesions could result in improved blood flow and oxygen delivery. Drugs targeting the distribution of blood flow in the microcirculatory environment of the muscle have the potential to better match oxygen delivery with

  18. Isoflurane Impairs Low-Frequency Feedback but Leaves High-Frequency Feedforward Connectivity Intact in the Fly Brain.

    Science.gov (United States)

    Cohen, Dror; van Swinderen, Bruno; Tsuchiya, Naotsugu

    2018-01-01

    Hierarchically organized brains communicate through feedforward (FF) and feedback (FB) pathways. In mammals, FF and FB are mediated by higher and lower frequencies during wakefulness. FB is preferentially impaired by general anesthetics in multiple mammalian species. This suggests FB serves critical functions in waking brains. The brain of Drosophila melanogaster (fruit fly) is also hierarchically organized, but the presence of FB in these brains is not established. Here, we studied FB in the fly brain, by simultaneously recording local field potentials (LFPs) from low-order peripheral structures and higher-order central structures. We analyzed the data using Granger causality (GC), the first application of this analysis technique to recordings from the insect brain. Our analysis revealed that low frequencies (0.1-5 Hz) mediated FB from the center to the periphery, while higher frequencies (10-45 Hz) mediated FF in the opposite direction. Further, isoflurane anesthesia preferentially reduced FB. Our results imply that the spectral characteristics of FF and FB may be a signature of hierarchically organized brains that is conserved from insects to mammals. We speculate that general anesthetics may induce unresponsiveness across species by targeting the mechanisms that support FB.

  19. Hysteresis of targeting civilians in armed conflicts

    OpenAIRE

    Uih Ran Lee

    2015-01-01

    This article explores warring groups’ intentional targeting behavior against civilians, a strictly prohibited war strategy by international norms. Using dynamic panel regressions run on a comprehensive dataset of contemporary warfare which covers 22 years (1989-2010), I find that warring actors, both sovereign states and formally organized armed groups, behave systematically in terms of civilian targeting when they are involved in prolonged armed conflict (15-22 years). Warring actors’ lethal...

  20. First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia.

    Science.gov (United States)

    Barone, Frank C; Gustafson, Deborah; Crystal, Howard A; Moreno, Herman; Adamski, Mateusz G; Arai, Ken; Baird, Alison E; Balucani, Clotilde; Brickman, Adam M; Cechetto, David; Gorelick, Philip; Biessels, Geert Jan; Kiliaan, Amanda; Launer, Lenore; Schneider, Julie; Sorond, Farzaneh A; Whitmer, Rachel; Wright, Clinton; Zhang, Zheng Gang

    2016-02-13

    As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international

  1. Mutational analysis of photosystem I polypeptides in the cyanobacterium Synechocystis sp. PCC 6803. Targeted inactivation of psaI reveals the function of psaI in the structural organization of psaL

    Science.gov (United States)

    Xu, Q.; Hoppe, D.; Chitnis, V. P.; Odom, W. R.; Guikema, J. A.; Chitnis, P. R.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    We cloned, characterized, and inactivated the psaI gene encoding a 4-kDa hydrophobic subunit of photosystem I from the cyanobacterium Synechocystis sp. PCC 6803. The psaI gene is located 90 base pairs downstream from psaL, and is transcribed on 0.94- and 0.32-kilobase transcripts. To identify the function of PsaI, we generated a cyanobacterial strain in which psaI has been interrupted by a gene for chloramphenicol resistance. The wild-type and the mutant cells showed comparable rates of photoautotrophic growth at 25 degrees C. However, the mutant cells grew slower and contained less chlorophyll than the wild-type cells, when grown at 40 degrees C. The PsaI-less membranes from cells grown at either temperature showed a small decrease in NADP+ photoreduction rate when compared to the wild-type membranes. Inactivation of psaI led to an 80% decrease in the PsaL level in the photosynthetic membranes and to a complete loss of PsaL in the purified photosystem I preparations, but had little effect on the accumulation of other photosystem I subunits. Upon solubilization with nonionic detergents, photosystem I trimers could be obtained from the wild-type, but not from the PsaI-less membranes. The PsaI-less photosystem I monomers did not contain detectable levels of PsaL. Therefore, a structural interaction between PsaL and PsaI may stabilize the association of PsaL with the photosystem I core. PsaL in the wild-type and PsaI-less membranes showed equal resistance to removal by chaotropic agents. However, PsaL in the PsaI-less strain exhibited an increased susceptibility to proteolysis. From these data, we conclude that PsaI has a crucial role in aiding normal structural organization of PsaL within the photosystem I complex and the absence of PsaI alters PsaL organization, leading to a small, but physiologically significant, defect in photosystem I function.

  2. Adiponectin deficiency exacerbates age-related hearing impairment

    Science.gov (United States)

    Tanigawa, T; Shibata, R; Ouchi, N; Kondo, K; Ishii, M; Katahira, N; Kambara, T; Inoue, Y; Takahashi, R; Ikeda, N; Kihara, S; Ueda, H; Murohara, T

    2014-01-01

    Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI. PMID:24763046

  3. Bar coded retroreflective target

    Science.gov (United States)

    Vann, Charles S.

    2000-01-01

    This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

  4. High Glucose Predisposes Gene Expression and ERK Phosphorylation to Apoptosis and Impaired Glucose-Stimulated Insulin Secretion via the Cytoskeleton

    Science.gov (United States)

    Yeo, Ronne Wee Yeh; Yang, Kaiyuan; Li, GuoDong; Lim, Sai Kiang

    2012-01-01

    Chronic high glucose (HG) inflicts glucotoxicity on vulnerable cell types such as pancreatic β cells and contributes to insulin resistance and impaired insulin secretion in diabetic patients. To identify HG-induced cellular aberrations that are candidate mediators of glucotoxicity in pancreatic β cells, we analyzed gene expression in ERoSHK6, a mouse insulin-secreting cell line after chronic HG exposure (six-day exposure to 33.3 mM glucose). Chronic HG exposure which reduced glucose-stimulated insulin secretion (GSIS) increased transcript levels of 185 genes that clustered primarily in 5 processes namely cellular growth and proliferation; cell death; cellular assembly and organization; cell morphology; and cell-to-cell signaling and interaction. The former two were validated by increased apoptosis of ERoSHK6 cells after chronic HG exposure and reaffirmed the vulnerability of β cells to glucotoxicity. The three remaining processes were partially substantiated by changes in cellular morphology and structure, and instigated an investigation of the cytoskeleton and cell-cell adhesion. These studies revealed a depolymerized actin cytoskeleton that lacked actin stress fibers anchored at vinculin-containing focal adhesion sites as well as loss of E-cadherin-mediated cell-cell adherence after exposure to chronic HG, and were concomitant with constitutive ERK1/2 phosphorylation that was refractory to serum and glucose deprivation. Although inhibition of ERK phosphorylation by PD98059 promoted actin polymerization, it increased apoptosis and GSIS impairment. These findings suggest that ERK phosphorylation is a proximate regulator of cellular processes targeted by chronic HG-induced gene expression and that dynamic actin polymerization and depolymerization is important in β cell survival and function. Therefore, chronic HG alters gene expression and signal transduction to predispose the cytoskeleton towards apoptosis and GSIS impairment. PMID:23024780

  5. Clinical characteristics and quality of life of older adults with cognitive impairment in Macao.

    Science.gov (United States)

    Lam Nogueira, Bernice O C; Li, Lu; Meng, Li-Rong; Ungvari, Gabor S; Ng, Chee H; Chiu, Helen F K; Kuok, Kenny C F; Tran, Linda; Xiang, Yu-Tao

    2018-02-06

    Little is known about the characteristics of older adults with cognitive impairment in Macao. This study aimed to determine the prevalence of cognitive impairment and the quality of life (QOL) of older adults living in the community and nursing homes. A consecutive sample of 413 subjects (199 from the community; 214 from nursing homes) was recruited and interviewed using standardized instruments. Cognition was measured with the Repeatable Battery for the Assessment of Neuropsychological Status and QOL with the brief version of the World Health Organization Quality of Life instrument. Altogether 87 subjects (21.0%) had cognitive impairment. On multivariate analyses, advanced age (P impairment. Married marital status (P = 0.01, OR = 0.3, 95%CI: 0.1-0.7) and higher education level (P impairment. After the confounders were controlled for, cognitive impairment was significantly associated with the lower psychological (F (11,412)  = 6.3, P = 0.01) and social relationship domains of QOL (F (11,412)  = 4.0, P = 0.04). Cognitive impairment was found to be common in community-dwelling and nursing home resident older adults in Macao. Given cognitive impairment's negative impact on QOL, appropriate strategies should be implemented to improve access to treatment in this population. © 2018 Japanese Psychogeriatric Society.

  6. Hearing impairment and ear diseases among children of school entry age in rural South India.

    Science.gov (United States)

    Rao, R S Phaneendra; Subramanyam, Malavika A; Nair, N Sreekumaran; Rajashekhar, B

    2002-06-17

    To find out the prevalence and causes of hearing impairment among children of school-entry age, in rural areas of coastal south India. The study adopted the World Health Organization (WHO) guidelines viz., "The Prevalence of Ear and Hearing Disorders Protocol". A total of 855 children studying in the first year of school were examined using a Portable Pure Tone Audiometer and an Otoscope. Children with hearing impairment were re-examined to find out the type of hearing impairment. Mothers of all children were interviewed in their homes, in order to obtain details of socio-economic status, family history and history of consanguinity. Hearing impairment was detected in 102 children (11.9%) and impacted wax was found to be the most common cause of hearing impairment (86.3%). On re-testing, it was predominantly conductive hearing impairment (81.6%) observed among 74 of these children. The prevalence of hearing impairment was significantly lower among children belonging to high socio-economic status (P=0.0036). Hearing impairment and preventable ear diseases were found to be important health problems among children of school-entry age group in this region. Regular screening of children of school-entry age will ensure that children begin their school-life without this disability.