Sample records for target organs impairment

  1. Hypertensive crisis with 2 target organ impairment induced by glycyrrhizin

    PubMed Central

    Li, Jing; Fan, Xiaoli; Wang, Qin

    2018-01-01

    Abstract Rationale: Glycyrrhizin is the main active component of licorice. Licorice and glycyrrhizin induced hypertension has been widely reported, yet licorice and glycyrrhizin induced hypertensive crisis has been rarely known. Patient concerns: The case of this report was a 47-year-old woman, who took 225 mg of glycyrrhizin daily for 3 years due to primary biliary cholangitis. She was found to have a dramatically elevated blood pressure of about 230/110 mmHg without a history of hypertension and was referred to the emergency department. Diagnoses: Hypokalemia, hypertensive retinopathy, and nephropathy were found during the following work-up. Since no other risk factors of hypertension were identified, she was suspected to have glycyrrhizin induced pseudo-hyperaldosteronism. Interventions: Glycyrrhizin was discontinued. Intravenous sodium nitroprusside was used during the first few days. Nifedipine and irbesartan were taken after discharge, and the dosage was reduced gradually under supervision. Outcomes: She stopped all the anti-hypertensive drugs 6 months since glycyrrhizin was stopped. Her blood pressure was about 110/60 mmHg after repetitive measurement. Her serum potassium and urine albumin/creatinine ratio were also normalized. Lessons: Licorice and glycyrrhizin induced hypertension due to pseudo-hyperaldosteronism has been widely reported, yet only 3 cases reported that excessive consumption of licorice could lead to hypertensive emergencies. This is the first case that glycyrrhizin induced hypertensive crisis with target organ impairment. By presenting this case, we remind clinicians of glycyrrhizin induced hypertension, a condition which could lead to medical emergencies. PMID:29538199

  2. Hypertensive crisis with 2 target organ impairment induced by glycyrrhizin: A case report.

    PubMed

    Li, Jing; Fan, Xiaoli; Wang, Qin

    2018-03-01

    Glycyrrhizin is the main active component of licorice. Licorice and glycyrrhizin induced hypertension has been widely reported, yet licorice and glycyrrhizin induced hypertensive crisis has been rarely known. The case of this report was a 47-year-old woman, who took 225 mg of glycyrrhizin daily for 3 years due to primary biliary cholangitis. She was found to have a dramatically elevated blood pressure of about 230/110 mmHg without a history of hypertension and was referred to the emergency department. Hypokalemia, hypertensive retinopathy, and nephropathy were found during the following work-up. Since no other risk factors of hypertension were identified, she was suspected to have glycyrrhizin induced pseudo-hyperaldosteronism. Glycyrrhizin was discontinued. Intravenous sodium nitroprusside was used during the first few days. Nifedipine and irbesartan were taken after discharge, and the dosage was reduced gradually under supervision. She stopped all the anti-hypertensive drugs 6 months since glycyrrhizin was stopped. Her blood pressure was about 110/60 mmHg after repetitive measurement. Her serum potassium and urine albumin/creatinine ratio were also normalized. Licorice and glycyrrhizin induced hypertension due to pseudo-hyperaldosteronism has been widely reported, yet only 3 cases reported that excessive consumption of licorice could lead to hypertensive emergencies. This is the first case that glycyrrhizin induced hypertensive crisis with target organ impairment. By presenting this case, we remind clinicians of glycyrrhizin induced hypertension, a condition which could lead to medical emergencies.

  3. Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice

    PubMed Central

    Mosca, Timothy J.; Hong, Weizhe; Dani, Vardhan S.; Favaloro, Vincenzo; Luo, Liqun

    2012-01-01

    Synapse assembly requires transsynaptic signals between the pre- and postsynapse1, but the understanding of essential organizational molecules remains incomplete2. Teneurins are conserved, EGF-repeat containing transmembrane proteins with large extracellular domains3. Here we show that two Drosophila Teneurins, Ten-m and Ten-a, are required for neuromuscular synapse organization and target selection. Ten-a is presynaptic while Ten-m is mostly postsynaptic; neuronal Ten-a and muscle Ten-m form a complex in vivo. Pre- or postsynaptic Teneurin perturbations cause severe synapse loss and impair many facets of organization transsynaptically and cell-autonomously. These include defects in active zone apposition, release sites, membrane and vesicle organization, and synaptic transmission. Moreover, the presynaptic microtubule and postsynaptic spectrin cytoskeletons are severely disrupted, suggesting a mechanism whereby Teneurins organize the cytoskeleton, which in turn affects other aspects of synapse development. Supporting this, Ten-m physically interacts with α-spectrin. Genetic analyses of teneurin and neuroligin reveal their differential roles that synergize to promote synapse assembly. Finally, at elevated endogenous levels, Ten-m regulates specific motoneuron-muscle target selection. Our study identifies the Teneurins as a key bi-directional transsynaptic signal in general synapse organization, and demonstrates that such a molecule can also regulate target selection. PMID:22426000

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

    PubMed

    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.

  5. 40 CFR 156.85 - Non-target organisms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Non-target organisms. 156.85 Section 156.85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS... Non-target organisms. (a) Requirement. Where a hazard exists to non-target organisms, EPA may require...

  6. 40 CFR 156.85 - Non-target organisms.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Non-target organisms. 156.85 Section 156.85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS... Non-target organisms. (a) Requirement. Where a hazard exists to non-target organisms, EPA may require...

  7. Dual inhibition of mTORC1 and mTORC2 perturbs cytoskeletal organization and impairs endothelial cell elongation.

    PubMed

    Tsuji-Tamura, Kiyomi; Ogawa, Minetaro

    2018-02-26

    Elongation of endothelial cells is an important process in vascular formation and is expected to be a therapeutic target for inhibiting tumor angiogenesis. We have previously demonstrated that inhibition of mTORC1 and mTORC2 impaired endothelial cell elongation, although the mechanism has not been well defined. In this study, we analyzed the effects of the mTORC1-specific inhibitor everolimus and the mTORC1/mTORC2 dual inhibitor KU0063794 on the cytoskeletal organization and morphology of endothelial cell lines. While both inhibitors equally inhibited cell proliferation, KU0063794 specifically caused abnormal accumulation of F-actin and disordered distribution of microtubules, thereby markedly impairing endothelial cell elongation and tube formation. The effects of KU0063794 were phenocopied by paclitaxel treatment, suggesting that KU0063794 might impair endothelial cell morphology through over-stabilization of microtubules. Although mTORC1 is a key signaling molecule in cell proliferation and has been considered a target for preventing angiogenesis, mTORC1 inhibitors have not been sufficient to suppress angiogenesis. Our results suggest that mTORC1/mTORC2 dual inhibition is more effective for anti-angiogenic therapy, as it impairs not only endothelial cell proliferation, but also endothelial cell elongation. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Placing blood on the target: a challenge for visually impaired persons.

    PubMed

    Cleary, M E; Hamilton, J E

    1993-01-01

    An individualized, blood glucose self-monitoring procedure for those who are visually impaired must be developed, taught, practiced, observed, and reviewed. Effective teaching requires understanding functional vision loss, observing safety precautions, organizing the work area, obtaining an adequate blood sample, ensuring accurate placement of blood on the strip, and cleaning up. Thoroughness and repetition enable the visually impaired person to perform the procedure safely and confidently.

  9. Impaired colour vision in workers exposed to organic solvents: A systematic review.

    PubMed

    Betancur-Sánchez, A M; Vásquez-Trespalacios, E M; Sardi-Correa, C

    2017-01-01

    To evaluate recent evidence concerning the relationship between the exposure to organic solvents and the impairment of colour vision. A bibliographic search was conducted for scientific papers published in the last 15 years, in the LILACS, PubMed, Science Direct, EBSCO, and Cochrane databases that included observational studies assessing the relationship between impairment in colour vision and exposure to organic solvents. Eleven studies were selected that were performed on an economically active population and used the Lanthony D-15 desaturated test (D-15d), measured the exposure to organic solvents, and included unexposed controls. It was found that there is a statistically significant relationship between the exposure to organic solvents and the presence of an impairment in colour vision. The results support the hypothesis that exposure to organic solvents could induce acquired dyschromatopsia. The evaluation of colour vision with the D-15d test is simple and sensitive for diagnosis. More studies need to be conducted on this subject in order to better understand the relationship between impaired colour vision and more severe side effects caused by this exposure. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Process quality indicators targeting cognitive impairment to support quality of care for older people with cognitive impairment in emergency departments.

    PubMed

    Schnitker, Linda M; Martin-Khan, Melinda; Burkett, Ellen; Beattie, Elizabeth R A; Jones, Richard N; Gray, Len C

    2015-03-01

    The objective of this study was to develop process quality indicators (PQIs) to support the improvement of care services for older people with cognitive impairment in emergency departments (ED). A structured research approach was taken for the development of PQIs for the care of older people with cognitive impairment in EDs, including combining available evidence with expert opinion (phase 1), a field study (phase 2), and formal voting (phase 3). A systematic review of the literature identified ED processes targeting the specific care needs of older people with cognitive impairment. Existing relevant PQIs were also included. By integrating the scientific evidence and clinical expertise, new PQIs were drafted and, along with the existing PQIs, extensively discussed by an advisory panel. These indicators were field tested in eight hospitals using a cohort of older persons aged 70 years and older. After analysis of the field study data (indicator prevalence, variability across sites), in a second meeting, the advisory panel further defined the PQIs. The advisory panel formally voted for selection of those PQIs that were most appropriate for care evaluation. In addition to seven previously published PQIs relevant to the care of older persons, 15 new indicators were created. These 22 PQIs were then field tested. PQIs designed specifically for the older ED population with cognitive impairment were only scored for patients with identified cognitive impairment. Following formal voting, a total of 11 PQIs were included in the set. These PQIs targeted cognitive screening, delirium screening, delirium risk assessment, evaluation of acute change in mental status, delirium etiology, proxy notification, collateral history, involvement of a nominated support person, pain assessment, postdischarge follow-up, and ED length of stay. This article presents a set of PQIs for the evaluation of the care for older people with cognitive impairment in EDs. The variation in indicator

  11. Conceptual Scoring of Lexical Organization in Bilingual Children with Language Impairment

    ERIC Educational Resources Information Center

    Holmström, Ketty; Salameh, Eva-Kristina; Nettelbladt, Ulrika; Dahlgren-Sandberg, Annika

    2016-01-01

    The aim was to evaluate conceptual scoring of lexical organization in bilingual children with language impairment (BLI) and to compare BLI performance with monolingual children with language impairment (MLI). Word associations were assessed in 15 BLI and 9 MLI children. BLI were assessed in Arabic and Swedish, MLI in Swedish only. A number of…

  12. Artificial neural network study on organ-targeting peptides

    NASA Astrophysics Data System (ADS)

    Jung, Eunkyoung; Kim, Junhyoung; Choi, Seung-Hoon; Kim, Minkyoung; Rhee, Hokyoung; Shin, Jae-Min; Choi, Kihang; Kang, Sang-Kee; Lee, Nam Kyung; Choi, Yun-Jaie; Jung, Dong Hyun

    2010-01-01

    We report a new approach to studying organ targeting of peptides on the basis of peptide sequence information. The positive control data sets consist of organ-targeting peptide sequences identified by the peroral phage-display technique for four organs, and the negative control data are prepared from random sequences. The capacity of our models to make appropriate predictions is validated by statistical indicators including sensitivity, specificity, enrichment curve, and the area under the receiver operating characteristic (ROC) curve (the ROC score). VHSE descriptor produces statistically significant training models and the models with simple neural network architectures show slightly greater predictive power than those with complex ones. The training and test set statistics indicate that our models could discriminate between organ-targeting and random sequences. We anticipate that our models will be applicable to the selection of organ-targeting peptides for generating peptide drugs or peptidomimetics.

  13. Lexical-Semantic Organization in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Sheng, Li; McGregor, Karla K.

    2010-01-01

    Purpose: 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. Method: Fourteen children with SLI, 14 age matches (AM), and 14 expressive…

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

    PubMed

    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 <10%, 90 (30.8%) had cardiovascular risk of 10-20% and 43 (14.7%) 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.

  15. Color vision impairments among shipyard workers exposed to mixed organic solvents, especially xylene.

    PubMed

    Lee, Eun-Hee; Paek, Domyung; Kho, Young Lim; Choi, Kyungho; Chae, Hong Jae

    2013-01-01

    We evaluated color vision impairment in workers exposed to organic solvents, especially xylene. Three groups of subjects, comprising 63 workers occupationally exposed to organic solvents, 122 non-exposed workers in the same industry, and 185 subjects from the general population as controls, were evaluated for color vision. Exposure to solvents was indirectly evaluated by measuring the concentration of a urinary metabolite. Color vision was assessed using the Lanthony Desaturated 15-hue (Lanthony D-15) panel. Color confusion index (CCI) values in the exposed group were significantly higher than in the non-exposed workers or the general population, after adjustment for age and education, and significantly correlated with the concentration of methylhippuric acid. Color vision impairments were detected more frequently among the exposed group, and the most common types were type III and complex impairments. The rate of type III impairments was 9.52% in the exposed group, 1.64% in the non-exposed group, and 1.62% in the general population. Our results support the hypothesis that acquired color vision impairments could be induced by exposure to xylene. Testing for color vision impairment is a relatively simple, non-invasive and sensitive diagnostic method for relatively low-level exposures to xylene. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor- Associated...3. DATES COVERED 31 Aug 2015 - 30 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting MEK5 Enhances Radiosensitivity of Human Prostate...therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to

  17. Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment.

    PubMed

    Andonegui, Graciela; Zelinski, Erin L; Schubert, Courtney L; Knight, Derrice; Craig, Laura A; Winston, Brent W; Spanswick, Simon C; Petri, Björn; Jenne, Craig N; Sutherland, Janice C; Nguyen, Rita; Jayawardena, Natalie; Kelly, Margaret M; Doig, Christopher J; Sutherland, Robert J; Kubes, Paul

    2018-05-03

    Sepsis-associated encephalopathy manifesting as delirium is a common problem in critical care medicine. In this study, patients that had delirium due to sepsis had significant cognitive impairments at 12-18 months after hospital discharge when compared with controls and Cambridge Neuropsychological Automated Test Battery-standardized scores in spatial recognition memory, pattern recognition memory, and delayed-matching-to-sample tests but not other cognitive functions. A mouse model of S. pneumoniae pneumonia-induced sepsis, which modeled numerous aspects of the human sepsis-associated multiorgan dysfunction, including encephalopathy, also revealed similar deficits in spatial memory but not new task learning. Both humans and mice had large increases in chemokines for myeloid cell recruitment. Intravital imaging of the brains of septic mice revealed increased neutrophil and CCR2+ inflammatory monocyte recruitment (the latter being far more robust), accompanied by subtle microglial activation. Prevention of CCR2+ inflammatory monocyte recruitment, but not neutrophil recruitment, reduced microglial activation and other signs of neuroinflammation and prevented all signs of cognitive impairment after infection. Therefore, therapeutically targeting CCR2+ inflammatory monocytes at the time of sepsis may provide a novel neuroprotective clinical intervention to prevent the development of persistent cognitive impairments.

  18. Macromolecular target prediction by self-organizing feature maps.

    PubMed

    Schneider, Gisbert; Schneider, Petra

    2017-03-01

    Rational drug discovery would greatly benefit from a more nuanced appreciation of the activity of pharmacologically active compounds against a diverse panel of macromolecular targets. Already, computational target-prediction models assist medicinal chemists in library screening, de novo molecular design, optimization of active chemical agents, drug re-purposing, in the spotting of potential undesired off-target activities, and in the 'de-orphaning' of phenotypic screening hits. The self-organizing map (SOM) algorithm has been employed successfully for these and other purposes. Areas covered: The authors recapitulate contemporary artificial neural network methods for macromolecular target prediction, and present the basic SOM algorithm at a conceptual level. Specifically, they highlight consensus target-scoring by the employment of multiple SOMs, and discuss the opportunities and limitations of this technique. Expert opinion: Self-organizing feature maps represent a straightforward approach to ligand clustering and classification. Some of the appeal lies in their conceptual simplicity and broad applicability domain. Despite known algorithmic shortcomings, this computational target prediction concept has been proven to work in prospective settings with high success rates. It represents a prototypic technique for future advances in the in silico identification of the modes of action and macromolecular targets of bioactive molecules.

  19. Impaired organic ion transport in proximal tubules of rats with Heymann nephritis.

    PubMed

    Park, E K; Hong, S K; Goldinger, J; Andres, G; Noble, B

    1985-10-01

    Organic ion transport across the basolateral membrane of proximal tubules was measured by means of the tissue slice technique in each of the four different stages of Heymann nephritis. Impairment of both organic anion and cation transport was detected early in Stage 2, and became more severe in Stage 3 of Heymann nephritis. The decreased transport function was associated with extensive damage to proximal tubule cells, including loss of brush border microvilli and basal infoldings. Despite these abnormalities of structure and function, oxygen consumption of proximal tubule cells remained essentially normal. Partial recovery of organic cation transport was noted late in Heymann nephritis (Stage 4). Recovery of the cation transport function was associated with a partial restoration of brush border microvilli and basal infoldings to proximal tubule cells. However, organic anion transport remained depressed throughout the entire course of disease. Impairment of organic ion transport in rats with Heymann nephritis appeared to result from damage to basolateral membrane transport elements rather than general deterioration of the metabolic machinery of proximal tubule cells. Decreased organic cation transport appeared to be the consequence of a reduction in the number of carrier sites, a phenomenon that could have resulted from decreased membrane surface area. However, the depression of organic anion transport was associated with decreased substrate affinity of the anion carrier, indicating that qualitative, rather than quantitative changes, were primarily responsible for that defect. Specific antibody-mediated damage to the anion transport elements in basolateral membranes of proximal tubules is postulated to occur in Heymann nephritis.

  20. Soil microbial community structure and target organisms under different fumigation treatments

    USDA-ARS?s Scientific Manuscript database

    Several high-value crop producers in California rely heavily on soil fumigants to control key diseases, nematodes, weeds and volunteer crops. Fumigants with broad biocidal activity can affect both target and non-target soil organisms. The ability of non-target soil organisms to recover after fumigat...

  1. Self-organizing team formation for target observation

    NASA Astrophysics Data System (ADS)

    Bowyer, Richard S.; Bogner, Robert E.

    2001-08-01

    Target observation is a problem where the application of multiple sensors can improve the probability of detection and observation of the target. Team formation is one method by which seemingly unsophisticated heterogeneous sensors may be organized to achieve a coordinated observation system. The sensors, which we shall refer to as agents, are situated in an area of interest with the goal of observing a moving target. We apply a team approach to this problem, which combines the strengths of individual agents into a cohesive entity - the team. In autonomous systems, the mechanisms that underlie the formation of a team are of interest. Teams may be formed by various mechanisms, which include an externally imposed grouping of agents, or an internally, self-organized (SO) grouping of agents. Internally motivated mechanisms are particularly challenging, but offer the benefit of being unsupervised, an important quality for groups of autonomous cooperating machines. This is the focus of our research. By studying natural systems such as colonies of ants, we obtain insight into these mechanisms of self organization. We propose that the team is an expression of a distributed agent-self, and that a particular realization of the agent-self exists, whilst the environmental conditions are conducive to that existence. We describe an algorithms for agent team formation that is inspired by the self-organizing behavior of ants, and describe simulation results for team formation amongst a lattice of networked sensors.

  2. Simultaneous cytofluorometric measurement of phagocytosis, burst production and killing of human phagocytes using Candida albicans and Staphylococcus aureus as target organisms.

    PubMed

    Salih, H R; Husfeld, L; Adam, D

    2000-05-01

    Polymorphonuclear leukocytes (PMN) play a central role in the elimination of most extracellular pathogens, and an impairment of their functions predisposes an individual towards local and systemic bacterial and fungal infections. Here we describe a rapid and easy-to-perform cytofluorometric assay for investigation of PMN activity using Candida albicans and Staphylococcus aureus as target organisms. Phagocytes were stained with anti-CD13-RPE antibody, and microorganisms were stained with calcein-AM. Oxidative burst production was measured by oxidation of dihydroethidium. The percentage of killed target organisms after ingestion was determined by staining with ethidium-homodimer-1 after lysis of human cells. The dyes and procedures used in this method were chosen after comparison of different stains and cell preparation techniques described in previous assays. Concerning phagocytosis, the percentages of active phagocytes and of ingested microorganisms were determined. Furthermore, the method allowed measurement of the resulting percentage of PMNs producing respiratory burst, and of the percentage of killed microorganisms. We minimized artifactual changes, which might have been the reason for the difficulties and conflicting results of other cytofluorometric methods. The described method provides a new whole blood cytofluorometric assay, which combines rapid and simple handling with high reproducibility of results obtained by investigation of PMN activity using Candida albicans and Staphylococcus aureus as target organisms.

  3. Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

    PubMed Central

    Baghcheghi, Yousef; Salmani, Hossein; Beheshti, Farimah; Hosseini, Mahmoud

    2017-01-01

    The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments. PMID:28584813

  4. [Organization of medico-genetic counseling for hereditary hearing impairment].

    PubMed

    Markova, T G

    2009-01-01

    High frequency of hereditary pathologies resulting in congenital and prelingual auditory inefficiency necessitates organization of readily available medico-genetic counseling services based at specialized centres and an integrated dispensary system for the observation of families at risk of hereditary hearing impairment and identification of high-risk groups among the general population. Correct clinical diagnosis provides a basis for the strategy of molecular-genetic examination of a given patient and members of his (her) family. Results of the examination can be used for family planning and the choice of measures for the prevention of recurrent cases. The objective of the present work was to draw up the main lines of cooperative activities of deafness specialists and geneticists, propose indications for medico-genetic counseling, and distinguish groups at high risk of development of hereditary hearing impairment among the affected subjects and in the general population. It is shown that the efficiency of measures for the prevention of hereditary hearing loss is directly related to the availability of medico-genetic aid and the degree of involvement of risk groups in the examination.

  5. Target organs in chronic bioassays of 533 chemical carcinogens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gold, L.S.; Slone, T.H.; Manley, N.B.

    1991-06-01

    A compendium of carcinogenesis bioassay results organized by target organ is presented for 533 chemicals that are carcinogenic in at least one species. This compendium is based primarily on experiments in rats or mice; results in hamsters, nonhuman primates, and dogs are also reported. The compendium can be used to identify chemicals that induce tumors at particular sites, and to determine whether target sites are the same for chemicals positive in more than one species. The Carcinogenic Potency Database (CPDB), which includes results of 3969 experiments, is used in the analysis. The published CPDB includes details on each test, andmore » literature references. Chemical carcinogens are reported for 35 different target organs in rats or mice. More than 80% of the carcinogens in each of these species are positive in at least one of the 8 most frequent target sites; liver, lung, mammary gland, stomach, vascular system, kidney, hematopoietic system, and urinary bladder. An analysis is presented of how well one can predict the carcinogenic response in mice from results in rats, or vice versa. Among chemicals tested in both species, 76% of rat carcinogens are positive in mice, and 71% of mouse carcinogens are positive in rats. Prediction is less accurate to the same target site: 52% of rat carcinogens are positive in the same site in mice, and 48% of mouse carcinogens are positive in the same site in rats. The liver is the most frequent site in common between rats and mice.« less

  6. Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy.

    PubMed

    Fan, Zhiliang; Feng, Xiaojuan; Fan, Zhigang; Zhu, Xingyuan; Yin, Shaohua

    2018-05-09

    Epilepsy is a type of refractory neurologic disorder mental disease, which is associated with cognitive impairments and memory dysfunction. However, the potential mechanisms of epilepsy are not well understood. Previous evidence has identified the voltage gated potassium channel complex (VGKC) as a target in various cohorts of patients with epilepsy. In the present study, the efficacy of an antibody against VGKC (anti‑VGKC) for the treatment of epilepsy in mice was investigated. A mouse model of lithium‑pilocarpine temporal lobe epilepsy was established and anti‑VGKC treatment was administered for 30 days. Memory impairment, anxiety, visual attention, inhibitory control and neuronal loss were measured in the mouse model of lithium‑pilocarpine temporal lobe epilepsy. The results revealed that epileptic mice treated with anti‑VGKC were able to learn the task and presented attention impairment, even a tendency toward impulsivity and compulsivity. It was also exhibited that anti‑VGKC treatment decreased neuronal loss in structures classically associated with attentional performance in hippocampus. Mice who received Anti‑VGKC treatment had inhibited motor seizures and hippocampal damage as compared with control mice. In conclusion, these results indicated that anti‑VGKC treatment may present benefits for improvements of the condition of motor attention impairment and cognitive competence, which suggests that VGKC may be a potential target for the treatment of epilepsy.

  7. Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

    PubMed Central

    Gamella-Pozuelo, Luis; Fuentes-Calvo, Isabel; Gómez-Marcos, Manuel A.; Recio-Rodriguez, José I.; Agudo-Conde, Cristina; Fernández-Martín, José L.; Cannata-Andía, Jorge B.; López-Novoa, José M.; García-Ortiz, Luis; Martínez-Salgado, Carlos

    2015-01-01

    Abstract The search for biomarkers of hypertension and diabetes-induced damage to multiple target organs is a priority. We analyzed the correlation between plasma cardiotrophin-1 (CT-1), a chemokine that participates in cardiovascular remodeling and organ fibrosis, and a wide range of parameters currently used to diagnose morphological and functional progressive injury in left ventricle, arteries, and kidneys of diabetic and hypertensive patients, in order to validate plasma levels of CT-1 as clinical biomarker. This is an observational study with 93 type 2-diabetic patients, 209 hypertensive patients, and 82 healthy controls in which we assessed the following parameters: plasma CT-1, basal glycaemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), left ventricular hypertrophy (LVH by electrocardiographic indexes), peripheral vascular disease (by pulse wave velocity—PWV, carotid intima-media thickness—C-IMT, and ankle-brachial index—ABI), and renal impairment (by microalbuminuria, albumin/creatinine urinary ratio, plasma creatinine concentrations, and glomerular filtration rate). Hypertensive or diabetic patients have higher plasma CT-1 than control patients. CT-1 positively correlates with basal glycaemia, SBP, DBP, PP, LVH, arterial damage (increased IMT, decreased ABI), and early renal damage (microalbuminuria, elevated albumin/creatinine ratio). CT-1 also correlates with increased 10-year cardiovascular risk. Multiple linear regression analysis confirmed that CT-1 was associated with arterial injury assessed by PWV, IMT, ABI, and cardiac damage evaluated by Cornell voltage duration product. Increases in plasma CT-1 are strongly related to the intensity of several parameters associated to target organ damage supporting further investigation of its diagnostic capacity as single biomarker of cardiovascular injury and risk and, possibly, of subclinical renal damage. PMID:26222851

  8. Self-organization and progenitor targeting generate stable patterns in planarian regeneration.

    PubMed

    Atabay, Kutay Deniz; LoCascio, Samuel A; de Hoog, Thom; Reddien, Peter W

    2018-04-27

    During animal regeneration, cells must organize into discrete and functional systems. We show that self-organization, along with patterning cues, govern progenitor behavior in planarian regeneration. Surgical paradigms allowed the manipulation of planarian eye regeneration in predictable locations and numbers, generating alternative stable neuroanatomical states for wild-type animals with multiple functional ectopic eyes. We used animals with multiple ectopic eyes and eye transplantation to demonstrate that broad progenitor specification, combined with self-organization, allows anatomy maintenance during regeneration. We propose a model for regenerative progenitors involving (i) migratory targeting cues, (ii) self-organization into existing or regenerating eyes, and (iii) a broad zone, associated with coarse progenitor specification, in which eyes can be targeted by progenitors. These three properties help explain how tissues can be organized during regeneration. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  9. Hearing or speech impairment - resources

    MedlinePlus

    Resources - hearing or speech impairment ... The following organizations are good resources for information on hearing impairment or speech impairment: Alexander Graham Bell Association for the Deaf and Hard of Hearing -- www.agbell. ...

  10. Emotion-induced impairments in speeded word recognition tasks.

    PubMed

    Zeelenberg, René; Bocanegra, Bruno R; Pecher, Diane

    2011-01-01

    Recent studies show that emotional stimuli impair the identification of subsequently presented, briefly flashed stimuli. In the present study, we investigated whether emotional distractors (primes) impaired target processing when presentation of the target stimulus was not impoverished. In lexical decision, animacy decision, rhyme decision, and nonword naming, targets were presented in such a manner that they were clearly visible (i.e., targets were not masked and presented until participants responded). In all tasks taboo-sexual distractors caused a slowdown in responding to the subsequent neutral target. Our results indicate that the detrimental effects of emotional distractors are not confined to paradigms in which visibility of the target is limited. Moreover, impairments were obtained even when semantic processing of stimuli was not required.

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

    PubMed Central

    Ofori, Sandra N; Odia, Osaretin J

    2014-01-01

    Background 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 marker of cardiovascular damage in our patient population. PMID:24833906

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

    PubMed

    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.

  13. Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia.

    PubMed

    Kesler, Shelli R; Gugel, Meike; Huston-Warren, Emily; Watson, Christa

    2016-05-01

    Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk for cognitive impairments that disrupt everyday functioning and decrease quality of life. The specific biological mechanisms underlying cognitive impairment following ALL remain largely unclear, but previous studies consistently demonstrate significant white matter pathology. We aimed to extend this literature by examining the organization of the white matter connectome in young patients with a history of ALL treated with chemotherapy only. We applied graph theoretical analysis to diffusion tensor imaging obtained from 31 survivors of ALL age 5-19 years and 39 matched healthy controls. Results indicated significantly lower small-worldness (p = 0.007) and network clustering coefficient (p = 0.019), as well as greater cognitive impairment (p = 0.027) in the ALL group. Regional analysis indicated that clustered connectivity in parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions was altered in the ALL group. Random forest analysis revealed a model of connectome and demographic variables that could automatically classify survivors of ALL as having cognitive impairment or not (accuracy = 0.89, p < 0.0001). These findings provide further evidence of brain injury in young survivors of ALL, even those without a history of central nervous system (CNS) disease or cranial radiation. Efficiency of local information processing, reorganization of hub connectivity, and cognitive reserve may contribute to cognitive outcome in these children. Certain connectome properties showed U-shaped relationships with cognitive impairment suggesting an optimal range of regional connectivity.

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

    PubMed

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

    2016-03-16

    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 method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

  15. D1 Receptor Activation in the Mushroom Bodies Rescues Sleep Loss Induced Learning Impairments in Drosophila

    PubMed Central

    Seugnet, Laurent; Suzuki, Yasuko; Vine, Lucy; Gottschalk, Laura; Shaw, Paul J

    2008-01-01

    Background Extended wakefulness disrupts acquisition of short term memories in mammals. However, the underlying molecular mechanisms triggered by extended waking and restored by sleep are unknown. Moreover, the neuronal circuits that depend on sleep for optimal learning remain unidentified. Results Learning was evaluated using Aversive Phototaxic Suppression (APS). In this task, flies learn to avoid light that is paired with an aversive stimulus (quinine /humidity). We demonstrate extensive homology in sleep deprivation induced learning impairment between flies and humans. Both 6 h and 12 h of sleep deprivation are sufficient to impair learning in Canton-S (Cs) flies. Moreover, learning is impaired at the end of the normal waking-day in direct correlation with time spent awake. Mechanistic studies indicate that this task requires intact mushroom bodies (MBs) and requires the Dopamine D1-like receptor (dDA1). Importantly, sleep deprivation induced learning impairments could be rescued by targeted gene expression of the dDA1 receptor to the MBs. Conclusion These data provide direct evidence that extended wakefulness disrupts learning in Drosophila. These results demonstrate that it is possible to prevent the effects of sleep deprivation by targeting a single neuronal structure and identify cellular and molecular targets adversely affected by extended waking in a genetically tractable model organism. PMID:18674913

  16. Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers.

    PubMed

    Song, W; Hwang, Y; Youngblood, V M; Cook, R S; Balko, J M; Chen, J; Brantley-Sieders, D M

    2017-10-05

    Basal-like/triple-negative breast cancers (TNBCs) are among the most aggressive forms of breast cancer, and disproportionally affects young premenopausal women and women of African descent. Patients with TNBC suffer a poor prognosis due in part to a lack of molecularly targeted therapies, which represents a critical barrier for effective treatment. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for TNBC. EphA2 expression is enriched in the basal-like molecular subtype in human breast cancers. Loss of EphA2 function in both human and genetically engineered mouse models of TNBC reduced tumor growth in culture and in vivo. Mechanistically, targeting EphA2 impaired cell cycle progression through S-phase via downregulation of c-Myc and stabilization of the cyclin-dependent kinase inhibitor p27/KIP1. A small molecule kinase inhibitor of EphA2 effectively suppressed tumor cell growth in vivo, including TNBC patient-derived xenografts. Thus, our data identify EphA2 as a novel molecular target for TNBC.

  17. Targeting EphA2 impairs cell cycle progression and growth of basal-like/triple-negative breast cancers

    PubMed Central

    Song, W; Hwang, Y; Youngblood, V M; Cook, R S; Balko, J M; Chen, J; Brantley-Sieders, D M

    2017-01-01

    Basal-like/triple-negative breast cancers (TNBCs) are among the most aggressive forms of breast cancer, and disproportionally affects young premenopausal women and women of African descent. Patients with TNBC suffer a poor prognosis due in part to a lack of molecularly targeted therapies, which represents a critical barrier for effective treatment. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for TNBC. EphA2 expression is enriched in the basal-like molecular subtype in human breast cancers. Loss of EphA2 function in both human and genetically engineered mouse models of TNBC reduced tumor growth in culture and in vivo. Mechanistically, targeting EphA2 impaired cell cycle progression through S-phase via downregulation of c-Myc and stabilization of the cyclin-dependent kinase inhibitor p27/KIP1. A small molecule kinase inhibitor of EphA2 effectively suppressed tumor cell growth in vivo, including TNBC patient-derived xenografts. Thus, our data identify EphA2 as a novel molecular target for TNBC. PMID:28581527

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

    PubMed

    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.

  19. HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses

    PubMed Central

    Col, Edwige; Caron, Cécile; Chable-Bessia, Christine; Legube, Gaelle; Gazzeri, Sylvie; Komatsu, Yasuhiko; Yoshida, Minoru; Benkirane, Monsef; Trouche, Didier; Khochbin, Saadi

    2005-01-01

    HIV-1 transactivator Tat uses cellular acetylation signalling by targeting several cellular histone acetyltransferases (HAT) to optimize its various functions. Although Tip60 was the first HAT identified to interact with Tat, the biological significance of this interaction has remained obscure. We had previously shown that Tat represses Tip60 HAT activity. Here, a new mechanism of Tip60 neutralization by Tat is described, where Tip60 is identified as a substrate for the newly reported p300/CBP-associated E4-type ubiquitin-ligase activity, and Tat uses this mechanism to induce the polyubiquitination and degradation of Tip60. Tip60 targeting by Tat results in a dramatic impairment of the Tip60-dependent apoptotic cell response to DNA damage. These data reveal yet unknown strategies developed by HIV-1 to increase cell resistance to genotoxic stresses and show a role of Tat as a modulator of cellular protein ubiquitination. PMID:16001085

  20. Metabolic syndrome indicators and target organ damage in urban active coping African and Caucasian men: the SABPA study.

    PubMed

    de Kock, A; Malan, L; Potgieter, J C; Steenekamp, W; van der Merwe, M T

    2012-05-01

    Psychosocial stress relating to an urban environment or acculturation increases the prevalence of metabolic syndrome (MetS). The objectives of this study were firstly to indicate and compare differences regarding appraisal of stress or active coping responses in urban African (n=88) and Caucasian (n=101) male teachers of South Africa, in accord with the prevalence of MetS indicators. And secondly to investigate the extent to which utilisation of active coping responses, together with MetS indicators, predict target organ damage, in these men. The Coping Strategy Indicator determined high and low active coping responses in male teachers from the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. SABPA inclusion and exclusion criteria were used. Additionally, diabetic medication users (n=8), and participants with renal impairment (n=2) or HIV positive (n=13), were excluded. MetS indicators included glucose, triglyceride, high-density lipoprotein cholesterol, blood pressure, and waist circumference, independent of confounders (age, physical activity, gamma glutamyl transferase). Microalbuminuria and carotid intima-media thickness indicated target organ damage. More MetS indicators exceeded the IDF cut-off points in high active coping African men (14.71%) than in their Caucasian counterparts (3.33%), as determined from χ² analyses. Furthermore, stepwise regressions indicated that more MetS indicators predicted endothelial dysfunction, especially in the high active coping African men. High active coping African men showed more manifestation of MetS, compared to their Caucasian counterparts, and revealed progress towards endothelial dysfunction. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  1. Hearing-Impaired Formal Inservice Program.

    ERIC Educational Resources Information Center

    Northeast Regional Media Center for the Deaf, Amherst, MA.

    The HI-FI (Hearing-Impaired Formal Inservice) Program is described as a set of inservice materials targeted for workshops of regular classroom teachers and other school personnel concerned with school district and classroom management of hearing impaired (HI) children. An introductory section focuses on the design of the program materials,…

  2. Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment.

    PubMed

    Yi, Li-Ye; Liang, Xia; Liu, Da-Ming; Sun, Bo; Ying, Sun; Yang, Dong-Bo; Li, Qing-Bin; Jiang, Chuan-Lu; Han, Ying

    2015-10-01

    Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown. We recruited 21 patients with svMCI and 26 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory-based network analyses were used to investigate alterations in the topological organization of functional brain networks. Compared with the HC individuals, the patients with svMCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the svMCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The svMCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within-module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the svMCI patients. Together, our results indicate that svMCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of svMCI. © 2015 John Wiley & Sons Ltd.

  3. Impaired Context Processing is Attributable to Global Neuropsychological Impairment in Schizophrenia and Psychotic Bipolar Disorder

    PubMed Central

    Hill, S. Kristian; Gold, James M.; Keefe, Richard S. E.; Clementz, Brett A.; Gershon, Elliot; Keshavan, Matcheri S.; Pearlson, Godfrey; Tamminga, Carol A.; Sweeney, John A.

    2017-01-01

    Abstract Background: Context processing may reflect a specific cognitive impairment in schizophrenia. Whether impaired context processing is observed across psychotic disorders or among relatives of affected individuals, and whether it is a deficit that is independent from the generalized neuropsychological deficits seen in psychotic disorders, are less established. Methods: Schizophrenia, schizoaffective, and psychotic bipolar probands (n = 660), their first-degree relatives (n = 741), and healthy individuals (n = 308) studied by the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium performed an expectancy task requiring use of contextual information to overcome a pre-potent response. Sensitivity for target detection and false alarm rates on trials requiring inhibition or goal maintenance were measured. Results: Proband groups and relatives with psychosis spectrum personality traits demonstrated reduced target sensitivity and elevated false alarm rates. False alarm rate was higher under inhibition vs goal maintenance conditions although this difference was attenuated in schizophrenia and schizoaffective proband groups. After accounting for global neuropsychological impairment, as reflected by the composite score from the Brief Assessment of Cognition in Schizophrenia neuropsychological battery, deficits in schizophrenia and bipolar proband groups were no longer significant. Performance measures were moderately familial. Conclusion: Reduced target detection, but not a specific deficit in context processing, is observed across psychotic disorders. Impairments in both goal maintenance and response inhibition appear to contribute comparably to deficits in schizophrenia and schizoaffective disorder, whereas greater difficulty with response inhibition underlies deficits in bipolar disorder. Yet, these deficits are not independent from the generalized neurocognitive impairment observed in schizophrenia and psychotic bipolar disorder. PMID:27306316

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

    PubMed

    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.

  5. Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

    PubMed

    Kim, Ji Yeon; Park, Keon Jae; Hwang, Joo-Yeon; Kim, Gyu Hee; Lee, DaeYeon; Lee, Yoo Jeong; Song, Eun Hyun; Yoo, Min-Gyu; Kim, Bong-Jo; Suh, Young Ho; Roh, Gu Seob; Gao, Bin; Kim, Won; Kim, Won-Ho

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with β-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development. Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants. ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration. Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D. Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for

  6. [Concomitant impact of organic pathology on the development of cognitive impairment in patients with attack-like paranoid schizophrenia].

    PubMed

    Libin, L Ia; Tagil'tseva, A V; Lifanova, D E; Ganzenko, M A; Gritsevskaia, T M; Ivanov, M B

    2014-01-01

    The study included 47 patients (23 men, 24 women) with ICD-10 diagnosis of attack-like paranoid schizophrenia. Patients were divided into two groups: with- (25 patients) or without (22 patients) a concomitant organic disease. Memory, attention and thinking were assessed with psychometric tests. Inter- and intra-group differences were identified that indicated a considerable impact of a concomitant CNS organic pathology on the development of cognitive impairment in the schizophrenic process and active antipsychotic therapy. The data obtained can be used in the development of a differentiated approach to the treatment of patients with concomitant organic pathology.

  7. Impaired Monoamine and Organic Cation Uptake in Choroid Plexus in Mice with Targeted Disruption of the Plasma Membrane Monoamine Transporter (Slc29a4) Gene*

    PubMed Central

    Duan, Haichuan; Wang, Joanne

    2013-01-01

    The choroid plexus (CP) forms the blood-cerebrospinal fluid (CSF) barrier and protects the brain from circulating metabolites, drugs, and toxins. The plasma membrane monoamine transporter (PMAT, SLC29A4) is a new polyspecific organic cation transporter that transports a wide variety of organic cations including biogenic amines, cationic drugs, and neurotoxins. PMAT is known to be expressed in the CP, but its specific role in CP transport of organic cations has not been clearly defined. Here we showed that PMAT transcript is highly expressed in human and mouse CPs, whereas transcripts of other functionally related transporters are minimally expressed in the CPs. Immunofluorescence staining further revealed that PMAT protein is localized to the apical (CSF-facing) membrane of the CP epithelium, consistent with a role of transporting organic cations from the CSF into CP epithelial cells. To further evaluate the role of PMAT in the CP, mice with targeted deletion of the Slc29a4 gene were generated and validated. Although Pmat−/− mice showed no overt abnormalities, the uptake of monoamines and the neurotoxin 1-methyl-4-phenylpyridinium was significantly reduced in CP tissues isolated from the knock-out mice. Together, our data demonstrated that PMAT is a major transporter for CP uptake of bioactive amines and xenobiotic cations. By removing its substrates from the CSF, PMAT may play an important role in protecting the brain from cationic neurotoxins and other potentially toxic organic cations. PMID:23255610

  8. Gender-related differences in adolescent hypertension and in target organ effects.

    PubMed

    Juhász, Mária; Katona, Eva; Settakis, Georgios; Paragh, György; Molnár, Csilla; Fülesdi, Béla; Páll, Dénes

    2010-04-01

    To assess whether a gender difference exists in adolescent hypertension and its target organ damage and to compare potential confounding factors and target organ damage in hypertensive and normotensive adolescent girls. From the Debrecen Hypertension Study, the anthropometric, blood pressure, and laboratory data as well as intima-media thickness (IMT) and left ventricular mass index (LVMI) of 58 hypertensive boys, 56 hypertensive girls, and 30 normotensive girls were analyzed. Both systolic and mean blood pressure values were higher in adolescent hypertensive boys than in girls. This difference was also present when comparing 24-hour average blood pressure values. Plasma concentrations of nitric oxide (NO) and endothelin-1 were not different in the two gender groups. IMT of the carotid arteries were similar in hypertensive boys and girls, but a significantly higher LVMI was detected in boys. A significant difference was detected in anthropometric data (height, weight, and body mass index [BMI]), plasma concentration of NO (lower levels in hypertensives), and IMT in hypertensive and normotensive girls (higher IMT in hypertensive girls). There is a difference between the severity of hypertension between hypertensive adolescent girls and boys. Hypertensive girls differ from normotensive girls not only in blood pressure values but also in risk factors and subclinical target organ effects. Further studies are needed to explain the gender differences in adolescent hypertension. The potential role of sex hormones in hypertensive teenagers also needs to be clarified in future works.

  9. Ultralow-Power Near Infrared Lamp Light Operable Targeted Organic Nanoparticle Photodynamic Therapy.

    PubMed

    Huang, Ling; Li, Zhanjun; Zhao, Yang; Zhang, Yuanwei; Wu, Shuang; Zhao, Jianzhang; Han, Gang

    2016-11-09

    Tissue penetration depth is a major challenge in practical photodynamic therapy (PDT). A biocompatible and highly effective near infrared (NIR)-light-absorbing carbazole-substituted BODIPY (Car-BDP) molecule is reported as a class of imaging-guidable deep-tissue activatable photosensitizers for PDT. Car-BDP possesses an intense, broad NIR absorption band (600-800 nm) with a remarkably high singlet oxygen quantum yield (Φ Δ = 67%). After being encapsulated with biodegradable PLA-PEG-FA polymers, Car-BDP can form uniform and small organic nanoparticles that are water-soluble and tumor-targetable. Rather than using laser light, such nanoparticles offer an unprecedented deep-tissue, tumor targeting photodynamic therapeutic effect by using an exceptionally low-power-density and cost-effective lamp light (12 mW cm -2 ). In addition, these nanoparticles can be simultaneously traced in vivo due to their excellent NIR fluorescence. This study signals a major step forward in photodynamic therapy by developing a new class of NIR-absorbing biocompatible organic nanoparticles for effective targeting and treatment of deep-tissue tumors. This work also provides a potential new platform for precise tumor-targeting theranostics and novel opportunities for future affordable clinical cancer treatment.

  10. Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice.

    PubMed

    Suzuki, Hidehiko; Nagatake, Takahiro; Nasu, Ayaka; Lan, Huangwenxian; Ikegami, Koji; Setou, Mitsutoshi; Hamazaki, Yoko; Kiyono, Hiroshi; Yagi, Kiyohito; Kondoh, Masuo; Kunisawa, Jun

    2018-02-13

    Vaccine delivery is an essential element for the development of mucosal vaccine, but it remains to be investigated how physical barriers such as mucus and cilia affect vaccine delivery efficacy. Previously, we reported that C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) targeted claudin-4, which is expressed by the epithelium associated with nasopharynx-associated lymphoid tissue (NALT), and could be effective as a nasal vaccine delivery. Mice lacking tubulin tyrosine ligase-like family, member 1 (Ttll1-KO mice) showed mucus accumulation in nasal cavity due to the impaired motility of respiratory cilia. Ttll1-KO mice nasally immunized with C-CPE fused to pneumococcal surface protein A (PspA-C-CPE) showed reduced PspA-specific nasal IgA responses, impaired germinal center formation, and decreased germinal center B-cells and follicular helper T cells in the NALT. Although there was no change in the expression of claudin-4 in the NALT epithelium in Ttll1-KO mice, the epithelium was covered by a dense mucus that prevented the binding of PspA-C-CPE to NALT. However, administration of expectorant N-acetylcysteine removed the mucus and rescued the PspA-specific nasal IgA response. These results show that the accumulation of mucus caused by impaired respiratory cilia function is an interfering factor in the C-CPE-based claudin-4-targeting nasal vaccine.

  11. The apelin-APJ axis: A novel potential therapeutic target for organ fibrosis.

    PubMed

    Huang, Shifang; Chen, Linxi; Lu, Liqun; Li, Lanfang

    2016-05-01

    Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is expressed in a diverse number of organs. The apelin-APJ axis helps to control the processes of pathological and physiological fibrosis, including renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis. However, the role of apelin-APJ in organ fibrosis remains controversial due to conflicting study results. The apelin-APJ axis is a detrimental mechanism which promotes liver fibrosis mainly via up-regulation the expression of collagen-II and platelet-derived growth factor receptor β (PDGFRβ). On the contrary, the apelin-APJ axis is beneficial for renal fibrosis, cardiac fibrosis and pulmonary fibrosis. The apelin-APJ axis alleviates renal fibrosis by restraining the expression of transforming growth factor-β1 (TGF-β1). In addition, the apelin-APJ axis attenuates cardiac fibrosis through multiple pathways. Furthermore, the apelin-APJ axis has beneficial effects on experimental bronchopulmonary dysplasia (BPD) and acute respiratory distress syndrome (ARDS) which suggest the apelin-APJ axis potentially alleviates pulmonary fibrosis. In this article, we review the controversies associated with apelin-APJ in organ fibrosis and introduce the drugs that target apelin-APJ. We conclude that future studies should place more emphasis on the relationship among apelin isoforms, APJ receptor subtypes and organ fibrosis. The apelin-APJ axis will be a potential therapeutic target and those drugs targeted for apelin-APJ may constitute a novel therapeutic strategy for renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Expanded Target-Chemical Analysis Reveals Extensive Mixed-Organic-Contaminant Exposure in U.S. Streams

    EPA Science Inventory

    Surface-water from 38 streams nation-wide was assessed using 14 target-organic methods (719 compounds). Designedbioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-org...

  13. E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer.

    PubMed

    Lopes-Ramos, Camila M; Barros, Bruna P; Koyama, Fernanda C; Carpinetti, Paola A; Pezuk, Julia; Doimo, Nayara T S; Habr-Gama, Angelita; Perez, Rodrigo O; Parmigiani, Raphael B

    2017-01-01

    Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.

  14. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.

  15. The myeloid-binding peptide adenoviral vector enables multi-organ vascular endothelial gene targeting.

    PubMed

    Lu, Zhi Hong; Kaliberov, Sergey; Zhang, Jingzhu; Muz, Barbara; Azab, Abdel K; Sohn, Rebecca E; Kaliberova, Lyudmila; Du, Yingqiu; Curiel, David T; Arbeit, Jeffrey M

    2014-08-01

    Vascular endothelial cells (ECs) are ideal gene therapy targets as they provide widespread tissue access and are the first contact surfaces following intravenous vector administration. Human recombinant adenovirus serotype 5 (Ad5) is the most frequently used gene transfer system because of its appreciable transgene payload capacity and lack of somatic mutation risk. However, standard Ad5 vectors predominantly transduce liver but not the vasculature following intravenous administration. We recently developed an Ad5 vector with a myeloid cell-binding peptide (MBP) incorporated into the knob-deleted, T4 fibritin chimeric fiber (Ad.MBP). This vector was shown to transduce pulmonary ECs presumably via a vector handoff mechanism. Here we tested the body-wide tropism of the Ad.MBP vector, its myeloid cell necessity, and vector-EC expression dose response. Using comprehensive multi-organ co-immunofluorescence analysis, we discovered that Ad.MBP produced widespread EC transduction in the lung, heart, kidney, skeletal muscle, pancreas, small bowel, and brain. Surprisingly, Ad.MBP retained hepatocyte tropism albeit at a reduced frequency compared with the standard Ad5. While binding specifically to myeloid cells ex vivo, multi-organ Ad.MBP expression was not dependent on circulating monocytes or macrophages. Ad.MBP dose de-escalation maintained full lung-targeting capacity but drastically reduced transgene expression in other organs. Swapping the EC-specific ROBO4 for the CMV promoter/enhancer abrogated hepatocyte expression but also reduced gene expression in other organs. Collectively, our multilevel targeting strategy could enable therapeutic biological production in previously inaccessible organs that pertain to the most debilitating or lethal human diseases.

  16. Morphological self-organizing feature map neural network with applications to automatic target recognition

    NASA Astrophysics Data System (ADS)

    Zhang, Shijun; Jing, Zhongliang; Li, Jianxun

    2005-01-01

    The rotation invariant feature of the target is obtained using the multi-direction feature extraction property of the steerable filter. Combining the morphological operation top-hat transform with the self-organizing feature map neural network, the adaptive topological region is selected. Using the erosion operation, the topological region shrinkage is achieved. The steerable filter based morphological self-organizing feature map neural network is applied to automatic target recognition of binary standard patterns and real-world infrared sequence images. Compared with Hamming network and morphological shared-weight networks respectively, the higher recognition correct rate, robust adaptability, quick training, and better generalization of the proposed method are achieved.

  17. Subcellular Targeting of Methylmercury Lyase Enhances Its Specific Activity for Organic Mercury Detoxification in Plants1

    PubMed Central

    Bizily, Scott P.; Kim, Tehryung; Kandasamy, Muthugapatti K.; Meagher, Richard B.

    2003-01-01

    Methylmercury is an environmental pollutant that biomagnifies in the aquatic food chain with severe consequences for humans and other animals. In an effort to remove this toxin in situ, we have been engineering plants that express the bacterial mercury resistance enzymes organomercurial lyase MerB and mercuric ion reductase MerA. In vivo kinetics experiments suggest that the diffusion of hydrophobic organic mercury to MerB limits the rate of the coupled reaction with MerA (Bizily et al., 2000). To optimize reaction kinetics for organic mercury compounds, the merB gene was engineered to target MerB for accumulation in the endoplasmic reticulum and for secretion to the cell wall. Plants expressing the targeted MerB proteins and cytoplasmic MerA are highly resistant to organic mercury and degrade organic mercury at 10 to 70 times higher specific activity than plants with the cytoplasmically distributed wild-type MerB enzyme. MerB protein in endoplasmic reticulum-targeted plants appears to accumulate in large vesicular structures that can be visualized in immunolabeled plant cells. These results suggest that the toxic effects of organic mercury are focused in microenvironments of the secretory pathway, that these hydrophobic compartments provide more favorable reaction conditions for MerB activity, and that moderate increases in targeted MerB expression will lead to significant gains in detoxification. In summary, to maximize phytoremediation efficiency of hydrophobic pollutants in plants, it may be beneficial to target enzymes to specific subcellular environments. PMID:12586871

  18. Impaired ability to organize information in individuals with autism spectrum disorders and their siblings.

    PubMed

    Sumiyoshi, Chika; Kawakubo, Yuki; Suga, Motomu; Sumiyoshi, Tomiki; Kasai, Kiyoto

    2011-03-01

    Despite rigorous research on disturbances of executive function and social cognition in autism spectrum disorders (ASD), little information has been available concerning higher cognitive functions, such as the ability to focus and associate relevant features to form categories, or 'organizing of information'. The purpose of this study was to investigate this issue by using the Wisconsin Card Sorting Test (WCST) and the Verbal Learning Task (VLT). Cognitive assessments were conducted in 22 individuals with ASD, 14 non-affected siblings, and 15 age-matched control subjects. Overall, individuals with ASD performed significantly worse on the WCST and VLT compared to their siblings and normal control subjects. Although siblings performed generally well on both tasks, they exhibited similar degree of perseverative responses in the WCST compared to the probands. A linear increase of the memory organization score in the VLT was also absent in siblings as well as the ASD group. These results suggest an impaired ability to organize information is one of the cognitive endophenotypes for ASD. Copyright © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  19. Liver - guardian, modifier and target of sepsis.

    PubMed

    Strnad, Pavel; Tacke, Frank; Koch, Alexander; Trautwein, Christian

    2017-01-01

    Sepsis and septic shock are characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The liver has a central role during sepsis, and is essential to the regulation of immune defence during systemic infections by mechanisms such as bacterial clearance, acute-phase protein or cytokine production and metabolic adaptation to inflammation. However, the liver is also a target for sepsis-related injury, including hypoxic hepatitis due to ischaemia and shock, cholestasis due to altered bile metabolism, hepatocellular injury due to drug toxicity or overwhelming inflammation, as well as distinct pathologies such as secondary sclerosing cholangitis in critically ill patients. Hence, hepatic dysfunction substantially impairs the prognosis of sepsis and serves as a powerful independent predictor of mortality in the intensive care unit. Sepsis is particularly problematic in patients with liver cirrhosis (who experience increased bacterial translocation from the gut and impaired microbial defence) as it can trigger acute-on-chronic liver failure - a syndrome with high short-term mortality. Here, we review the importance of the liver as a guardian, modifier and target of sepsis, the factors that contribute to sepsis in patients with liver cirrhosis and new therapeutic strategies.

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

    PubMed

    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.

  1. Targeted organ generation using Mixl1-inducible mouse pluripotent stem cells in blastocyst complementation.

    PubMed

    Kobayashi, Toshihiro; Kato-Itoh, Megumi; Nakauchi, Hiromitsu

    2015-01-15

    Generation of functional organs from patients' own cells is one of the ultimate goals of regenerative medicine. As a novel approach to creation of organs from pluripotent stem cells (PSCs), we employed blastocyst complementation in organogenesis-disabled animals and successfully generated PSC-derived pancreas and kidneys. Blastocyst complementation, which exploits the capacity of PSCs to participate in forming chimeras, does not, however, exclude contribution of PSCs to the development of tissues-including neural cells or germ cells-other than those specifically targeted by disabling of organogenesis. This fact provokes ethical controversy if human PSCs are to be used. In this study, we demonstrated that forced expression of Mix-like protein 1 (encoded by Mixl1) can be used to guide contribution of mouse embryonic stem cells to endodermal organs after blastocyst injection. We then succeeded in applying this method to generate functional pancreas in pancreatogenesis-disabled Pdx1 knockout mice using a newly developed tetraploid-based organ-complementation method. These findings hold promise for targeted organ generation from patients' own PSCs in livestock animals.

  2. Impairments of colour vision induced by organic solvents: a meta-analysis study.

    PubMed

    Paramei, Galina V; Meyer-Baron, Monika; Seeber, Andreas

    2004-09-01

    The impairment of colour discrimination induced by occupational exposure to toluene, styrene and mixtures of organic solvents is reviewed and analysed using a meta-analytical approach. Thirty-nine studies were surveyed covering a wide range of exposure conditions. Those studies using the Lanthony Panel D-15 desaturated test (D-15d) were further considered. From these for 15 samples data on colour discrimination ability (Colour Confusion Index, CCI) and exposure levels were provided, required for the meta-analysis. In accordance with previously reported higher CCI values for the exposed groups, the computations yielded positive effect sizes for 13 of the 15 samples, indicating that in the great majority of the studies the exposed groups showed inferior colour discrimination. However, the meta-analysis showed great variation in effect sizes across the studies. Possible reasons for inconsistency among the reported findings are discussed. These pertain to exposure-related parameters, as well as to confounders such as conditions of test administration and characteristics of subject samples. Those factors vary considerably among the studies and might have greatly contributed to divergence in measured colour vision capacity, thereby obscuring consistent effects of organic solvents on colour discrimination.

  3. Interarm blood pressure difference and target organ damage in the general population.

    PubMed

    Johansson, Jouni K; Puukka, Pauli J; Jula, Antti M

    2014-02-01

    The objective of the study was to investigate interarm differences of blood pressure (BP) and its determinants, and to clarify whether both arms are equally good in assessing BP and target organ damage in the general population. We studied a representative sample of Finnish adult population with 484 study participants, ages 25-74 years. BP was measured twice by an oscillometric monitor simultaneously on both arms. Study participants underwent a clinical examination including measurements of serum lipids, glucose and indicators of target organ damage. BP was 2.3/0.2 mmHg higher on right than on left arm (P < 0.001/P = 0.15 for SBP/DBP differences). SBP and DBP measured on right and left arms correlated equally with left ventricular mass index (LVMI), interventricular septal thickness (IVST), posterior wall thickness (PWT), pulse wave velocity (PWV) and albuminuria. Higher SBP level was an independent determinant of both greater systolic and diastolic interarm BP difference. Exaggerated absolute diastolic interarm BP difference (>5 mmHg) was associated with higher BMI, arm circumference, LVMI, IVST and PWT, whereas exaggerated absolute systolic interarm BP difference (>10 mmHg) was not associated with any clinical variables. There was only a small difference in BP between arms in a healthy general population. Both arms are equally good determinants of target organ damage. BP should be measured at least once on both arms and prefer the arm with higher BP readings in the future BP measurements.

  4. Platelets and Multi-Organ Failure in Sepsis.

    PubMed

    Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

    2017-10-20

    Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  5. Platelets and Multi-Organ Failure in Sepsis

    PubMed Central

    Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

    2017-01-01

    Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models. PMID:29053592

  6. Assessing and addressing cognitive impairment in bipolar disorder: the International Society for Bipolar Disorders Targeting Cognition Task Force recommendations for clinicians.

    PubMed

    Miskowiak, K W; Burdick, K E; Martinez-Aran, A; Bonnin, C M; Bowie, C R; Carvalho, A F; Gallagher, P; Lafer, B; López-Jaramillo, C; Sumiyoshi, T; McIntyre, R S; Schaffer, A; Porter, R J; Purdon, S; Torres, I J; Yatham, L N; Young, A H; Kessing, L V; Vieta, E

    2018-05-01

    Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and address cognitive impairment. The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face-to-face meeting, telephone conference call and email exchanges. Consensus-based recommendations were achieved through these exchanges with no need for formal consensus methods. The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy-to-administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence-based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments. This task force paper provides the first consensus-based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients' functional recovery and improve their quality of life. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Upper Limb Kinematics in Stroke and Healthy Controls Using Target-to-Target Task in Virtual Reality.

    PubMed

    Hussain, Netha; Alt Murphy, Margit; Sunnerhagen, Katharina S

    2018-01-01

    Kinematic analysis using virtual reality (VR) environment provides quantitative assessment of upper limb movements. This technique has rarely been used in evaluating motor function in stroke despite its availability in stroke rehabilitation. To determine the discriminative validity of VR-based kinematics during target-to-target pointing task in individuals with mild or moderate arm impairment following stroke and in healthy controls. Sixty-seven participants with moderate (32-57 points) or mild (58-65 points) stroke impairment as assessed with Fugl-Meyer Assessment for Upper Extremity were included from the Stroke Arm Longitudinal study at the University of Gothenburg-SALGOT cohort of non-selected individuals within the first year of stroke. The stroke groups and 43 healthy controls performed the target-to-target pointing task, where 32 circular targets appear one after the other and disappear when pointed at by the haptic handheld stylus in a three-dimensional VR environment. The kinematic parameters captured by the stylus included movement time, velocities, and smoothness of movement. The movement time, mean velocity, and peak velocity were discriminative between groups with moderate and mild stroke impairment and healthy controls. The movement time was longer and mean and peak velocity were lower for individuals with stroke. The number of velocity peaks, representing smoothness, was also discriminative and significantly higher in both stroke groups (mild, moderate) compared to controls. Movement trajectories in stroke more frequently showed clustering (spider's web) close to the target indicating deficits in movement precision. The target-to-target pointing task can provide valuable and specific information about sensorimotor impairment of the upper limb following stroke that might not be captured using traditional clinical scale. The trial was registered with register number NCT01115348 at clinicaltrials.gov, on May 4, 2010. URL: https://clinicaltrials.gov/ct2

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

    PubMed

    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.

  9. Spatial Cytoskeleton Organization Supports Targeted Intracellular Transport

    NASA Astrophysics Data System (ADS)

    Hafner, Anne E.; Rieger, Heiko

    2018-03-01

    The efficiency of intracellular cargo transport from specific source to target locations is strongly dependent upon molecular motor-assisted motion along the cytoskeleton. Radial transport along microtubules and lateral transport along the filaments of the actin cortex underneath the cell membrane are characteristic for cells with a centrosome. The interplay between the specific cytoskeleton organization and the motor performance realizes a spatially inhomogeneous intermittent search strategy. In order to analyze the efficiency of such intracellular search strategies we formulate a random velocity model with intermittent arrest states. We evaluate efficiency in terms of mean first passage times for three different, frequently encountered intracellular transport tasks: i) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane, ii) the reaction problem, which considers the binding time of two particles within the cell, and iii) the reaction-escape problem, which arises when cargo must be released at a synapse only after pairing with another particle. Our results indicate that cells are able to realize efficient search strategies for various intracellular transport tasks economically through a spatial cytoskeleton organization that involves only a narrow actin cortex rather than a cell body filled with randomly oriented actin filaments.

  10. Do insect repellents induce drift behaviour in aquatic non-target organisms?

    PubMed

    Fink, Patrick; Moelzner, Jana; Berghahn, Ruediger; von Elert, Eric

    2017-01-01

    Synthetic insect repellents are compounds applied to surfaces to discourage insects, mainly mosquitoes, from landing on those surfaces. As some of these repellents have repeatedly been detected in surface waters at significant concentrations, they may also exert repellent effects on aquatic non-target organisms. In running water systems, aquatic invertebrates actively enter downstream drift in order to avoid unfavourable environmental conditions. We thus tested the hypothesis that the widely used insect repellents DEET (N,N-Diethyl-m-toluamide), EBAAP (3-[N-butyl-N-acetyl]-aminopropionic acid ethyl ester) and Icaridin (1-piperidinecarboxylic acid 2-(2-hydroxyethyl)-1-methylpropyl ester) induce downstream drift behaviour in the aquatic invertebrates Gammarus pulex (Crustacea, Amphipoda) and Cloeon dipterum (Insecta, Ephemeroptera), using a laboratory-scale drift assay. We found no clear increase in the drift behaviour of both invertebrate species across a concentration gradient of eight orders of magnitude and even beyond maximum environmental concentrations for any of the three repellents. We found no evidence for a direct drift-inducing activity of insect repellents on aquatic non-target organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    Chandramouli, Kondethimmanahalli H.; Xu, Ying; Pan, Ke; Wang, Wen-Xiong; Qian, Pei-Yuan

    2011-01-01

    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. PMID:21897857

  12. Organization of Circadian Behavior Relies on Glycinergic Transmission.

    PubMed

    Frenkel, Lia; Muraro, Nara I; Beltrán González, Andrea N; Marcora, María S; Bernabó, Guillermo; Hermann-Luibl, Christiane; Romero, Juan I; Helfrich-Förster, Charlotte; Castaño, Eduardo M; Marino-Busjle, Cristina; Calvo, Daniel J; Ceriani, M Fernanda

    2017-04-04

    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. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Surface target-tracking guidance by self-organizing formation flight of fixed-wing UAV

    NASA Astrophysics Data System (ADS)

    Regina, N.; Zanzi, M.

    This paper presents a new concept of ground target surveillance based on a formation flight of two Unmanned Aerial Vehicles (UAVs) of fixed-wing type. Each UAV considered in this work has its own guidance law specifically designed for two different aims. A self organizing non-symmetric collaborative surveying scheme has been developed based on pursuers with different roles: the close-up-pursuer and the distance-pursuer. The close-up-pursuer behaves according to a guidance law which takes it to continually over-fly the target, also optimizing flight endurance. On the other hand, the distancepursuer behaves so as to circle around the target by flying at a certain distance and altitude from it; moreover, its motion ensures the maximum “ seeability” of the ground based target. In addition, the guidance law designed for the distance-pursuer also implements a collision avoidance feature in order to prevent possible risks of collision with the close-up-pursuer during the tracking maneuvers. The surveying scheme is non-symmetric in the sense that the collision avoidance feature is accomplished by a guidance law implemented only on one of the two pursuers; moreover, it is collaborative because the surveying is performed by different tasks of two UAVs and is self-organizing because, due to the collision avoidance feature, target tracking does not require pre-planned collision-risk-free trajectories but trajectories are generated in real time.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 thatmore » 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.« less

  15. Differences in DNA Binding Specificity of Floral Homeotic Protein Complexes Predict Organ-Specific Target Genes.

    PubMed

    Smaczniak, Cezary; Muiño, Jose M; Chen, Dijun; Angenent, Gerco C; Kaufmann, Kerstin

    2017-08-01

    Floral organ identities in plants are specified by the combinatorial action of homeotic master regulatory transcription factors. However, how these factors achieve their regulatory specificities is still largely unclear. Genome-wide in vivo DNA binding data show that homeotic MADS domain proteins recognize partly distinct genomic regions, suggesting that DNA binding specificity contributes to functional differences of homeotic protein complexes. We used in vitro systematic evolution of ligands by exponential enrichment followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- and heterodimers to measure their DNA binding specificities. We show that specification of reproductive organs is associated with distinct binding preferences of a complex formed by SEPALLATA3 and AGAMOUS. Binding specificity is further modulated by different binding site spacing preferences. Combination of SELEX-seq and genome-wide DNA binding data allows differentiation between targets in specification of reproductive versus perianth organs in the flower. We validate the importance of DNA binding specificity for organ-specific gene regulation by modulating promoter activity through targeted mutagenesis. Our study shows that intrafamily protein interactions affect DNA binding specificity of floral MADS domain proteins. Differential DNA binding of MADS domain protein complexes plays a role in the specificity of target gene regulation. © 2017 American Society of Plant Biologists. All rights reserved.

  16. The modality-specific organization of grammatical categories: evidence from impaired spoken and written sentence production.

    PubMed

    Rapp, B; Caramazza, A

    1997-02-01

    We describe the case of a brain-damaged individual whose speech is characterized by difficulty with practically all words except for elements of the closed class vocabulary. In contrast, his written sentence production exhibits a complementary impairment involving the omission of closed class vocabulary items and the relative sparing of nouns. On the basis of these differences we argue: (1) that grammatical categories constitute an organizing parameter of representation and/or processing for each of the independent, modality-specific lexicons, and (2) that these observations contribute to the growing evidence that access to the orthographic and phonological forms of words can occur independently.

  17. Impaired reproduction of mallards fed an organic form of selenium

    USGS Publications Warehouse

    Heinz, G.H.; Hoffman, D.J.; Gold, L.G.

    1989-01-01

    We fed mallards (Anas platyrhynchos) diets supplemented with 0-, 1-, 2-, 4-, 8-, or 16-ppm selenium in the form of selenomethionine. We fed another group of mallards a diet containing 16-ppm selenium as selenocystine. Females fed the control diet produced a mean of 8.1 ducklings that survived to 6 days of age, which was significantly greater than the 4.6 young produced by females fed 8-ppm selenium as selenomethionine and the zero surviving young of females fed 16-ppm selenium as selenomethionine. Selenocystine did not impair reproduction. Diets containing 8- and 16-ppm selenium as selenomethionine caused malformations in 6.8 and 67.9%, respectively, of unhatched eggs compared with 0.6% for controls. The most common malformations were of eyes, bill, legs, and feet. Selenium did not affect the onset or frequency of egg laying, egg size, shell thickness, fertility of eggs, or sex ratio of ducklings. Reduced survival and growth occurred in ducklings hatched from groups whose parents had received 8- or 16-ppm selenium as selenomethionine, even though all ducklings were fed a control diet. Concentrations of selenium in eggs and liver of adults could be predicted from dietary concentrations. We conclude that the dietary threshold of selenium as selenomethionine necessary to impair reproduction is between 4 and 8 ppm. It is difficult to identify 1 level of selenium in eggs that will be diagnostic of reproductive impairment in the field because different chemical forms of selenium appear to have different toxicities in eggs. However, when eggs from a wild population contain .gtoreq. 1-ppm selenium on a wet-weight basis, reproductive impairment may be possible and should be evaluated in that population. At 5-ppm selenium in eggs, reproductive impairment is much more likely to occur.

  18. Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts.

    PubMed

    Comito, Giuseppina; Pons Segura, Coral; Taddei, Maria Letizia; Lanciotti, Michele; Serni, Sergio; Morandi, Andrea; Chiarugi, Paola; Giannoni, Elisa

    2017-01-03

    Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. However, it has been recently proposed that ZA could have direct anti-tumour effects, although the molecular mechanism is unknown. We herein unravel a novel anti-tumour activity of ZA in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. Particularly, we demonstrate that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumour cells and their pro-angiogenic features. Crucially, ZA administration reverts cancer associated fibroblasts (CAFs) activation by targeting the mevalonate pathway and RhoA geranyl-geranylation, thereby impairing smooth muscle actin-α fibers organization, a prerequisite of fibroblast activation. Moreover, ZA prevents the M2 macrophages-mediated activation of normal fibroblast, highlighting the broad efficacy of this drug on tumour microenvironment. These results are confirmed in a metastatic xenograft PCa mouse model in which ZA-induced stromal normalization impairs cancer-stromal cells crosstalk, resulting in a significant reduction of primary tumour growth and metastases. Overall these findings reinforce the efficacy of ZA as a potential therapeutic approach to reduce cancer aggressiveness, by abrogating the supportive role of tumour microenvironment.

  19. Targeting proteasomes in infectious organisms to combat disease.

    PubMed

    Bibo-Verdugo, Betsaida; Jiang, Zhenze; Caffrey, Conor R; O'Donoghue, Anthony J

    2017-05-01

    Proteasomes are multisubunit, energy-dependent, proteolytic complexes that play an essential role in intracellular protein turnover. They are present in eukaryotes, archaea, and in some actinobacteria species. Inhibition of proteasome activity has emerged as a powerful strategy for anticancer therapy and three drugs have been approved for treatment of multiple myeloma. These compounds react covalently with a threonine residue located in the active site of a proteasome subunit to block protein degradation. Proteasomes in pathogenic organisms such as Mycobacterium tuberculosis and Plasmodium falciparum also have a nucleophilic threonine residue in the proteasome active site and are therefore sensitive to these anticancer drugs. This review summarizes efforts to validate the proteasome in pathogenic organisms as a therapeutic target. We describe several strategies that have been used to develop inhibitors with increased potency and selectivity for the pathogen proteasome relative to the human proteasome. In addition, we highlight a cell-based chemical screening approach that identified a potent, allosteric inhibitor of proteasomes found in Leishmania and Trypanosoma species. Finally, we discuss the development of proteasome inhibitors as anti-infective agents. © 2017 Federation of European Biochemical Societies.

  20. Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

    PubMed

    Harjola, Veli-Pekka; Mullens, Wilfried; Banaszewski, Marek; Bauersachs, Johann; Brunner-La Rocca, Hans-Peter; Chioncel, Ovidiu; Collins, Sean P; Doehner, Wolfram; Filippatos, Gerasimos S; Flammer, Andreas J; Fuhrmann, Valentin; Lainscak, Mitja; Lassus, Johan; Legrand, Matthieu; Masip, Josep; Mueller, Christian; Papp, Zoltán; Parissis, John; Platz, Elke; Rudiger, Alain; Ruschitzka, Frank; Schäfer, Andreas; Seferovic, Petar M; Skouri, Hadi; Yilmaz, Mehmet Birhan; Mebazaa, Alexandre

    2017-07-01

    Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spence, Jeffrey R.; Go, Minjoung M.; Bahmanyar, S.

    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,more » 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.« less

  2. A New Method Without Organic Solvent to Targeted Nanodrug for Enhanced Anticancer Efficacy

    NASA Astrophysics Data System (ADS)

    Wu, Shichao; Yang, Xiangrui; Zou, Mingyuan; Hou, Zhenqing; Yan, Jianghua

    2017-06-01

    Since the hydrophobic group is always essential to the synthesis of the drug-loaded nanoparticles, a majority of the methods rely heavily on organic solvent, which may not be completely removed and might be a potential threat to the patients. In this study, we completely "green" synthesized 10-hydroxycamptothecine (HCPT) loaded, folate (FA)-modified nanoneedles (HFNDs) for highly efficient cancer therapy with high drug loading, targeting property, and imaging capability. It should be noted that no organic solvent was used in the preparation process. In vitro cell uptake study and the in vivo distribution study showed that the HFNDs, with FA on the surface, revealed an obviously targeting property and entered the HeLa cells easier than the chitosan-HCPT nanoneedles without FA modified (NDs). The cytotoxicity tests illustrated that the HFNDs possessed better killing ability to HeLa cells than the individual drug or the NDs in the same dose, indicating its good anticancer effect. The in vivo anticancer experiment further revealed the pronounced anticancer effects and the lower side effects of the HFNDs. This new method without organic solvent will lead to a promising sustained drug delivery system for cancer diagnosis and treatment.

  3. THE EPITHELIUM AS A TARGET IN SEPSIS.

    PubMed

    Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gómez, Alonso; Murray, Patrick; Gómez, Hernando; Kellum, John A

    2016-03-01

    Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future.

  4. Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ.

    PubMed

    Stucki, David M; Ruegsegger, Céline; Steiner, Silvio; Radecke, Julika; Murphy, Michael P; Zuber, Benoît; Saxena, Smita

    2016-08-01

    Spinocerebellar ataxia type 1 (SCA1), due to an unstable polyglutamine expansion within the ubiquitously expressed Ataxin-1 protein, leads to the premature degeneration of Purkinje cells (PCs), decreasing motor coordination and causing death within 10-15 years of diagnosis. Currently, there are no therapies available to slow down disease progression. As secondary cellular impairments contributing to SCA1 progression are poorly understood, here, we focused on identifying those processes by performing a PC specific proteome profiling of Sca1(154Q/2Q) mice at a symptomatic stage. Mass spectrometry analysis revealed prominent alterations in mitochondrial proteins. Immunohistochemical and serial block-face scanning electron microscopy analyses confirmed that PCs underwent age-dependent alterations in mitochondrial morphology. Moreover, colorimetric assays demonstrated impairment of the electron transport chain complexes (ETC) and decrease in ATPase activity. Subsequently, we examined whether the mitochondria-targeted antioxidant MitoQ could restore mitochondrial dysfunction and prevent SCA1-associated pathology in Sca1(154Q/2Q) mice. MitoQ treatment both presymptomatically and when symptoms were evident ameliorated mitochondrial morphology and restored the activities of the ETC complexes. Notably, MitoQ slowed down the appearance of SCA1-linked neuropathology such as lack of motor coordination as well as prevented oxidative stress-induced DNA damage and PC loss. Our work identifies a central role for mitochondria in PC degeneration in SCA1 and provides evidence for the supportive use of mitochondria-targeted therapeutics in slowing down disease progression. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

    PubMed

    Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

    2015-01-01

    The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

  6. Target organ damage in hypertensive patients of different ethnic groups.

    PubMed

    Wolak, Talya; Anfanger, Sharon; Wolak, Arik; Furman, Tsilla; Abuara'ar, Touphic; Biton, Amnon; Pilpel, Dina; Paran, Esther

    2007-03-20

    Hypertension is associated with involvement of target organs which varies among the different ethnic groups. The multiplicity of the population in Israel offers an opportunity for evaluating target organ damage in hypertensive patients of different ethnic origins. Data were collected from the computerized medical files of hypertensive patients in primary care clinics. The analysis was done on 576 hypertensive patients: 138 Bedouins (Arab residents), 141 Sephardic Jews (immigrants from North Africa and the Middle East), 152 Asian-Indian Jews (immigrants from India) and 145 Ashkenazi Jews (immigrants from Europe and North and South America). In multivariable logistic regressions adjusted for known risk factors and ethnicity, the prevalence of cerebrovascular disease was the highest among the Asian-Indian Jews (OR=3.09, p value=0.009). Renal damage was highest among the Bedouins (OR=4.54, p value<0.0001) and Asian-Indian Jews (OR=2.88, p value=0.005). The differences in the prevalence of renal damage among the various ethnic groups were even more pronounced among patients without diabetes (OR=8.31, p value<0.0001 in Bedouins and OR=7.46, p value=0.001 in Asian-Indian Jews). The prevalence of ischemic heart disease did not differ significantly among the four ethnic groups. The prevalence of cerebrovascular and renal diseases are both significantly associated with ethnic origin of Asian-Indian Jews and Bedouins. However, the multivariate analysis shows that the prevalence of ischemic heart disease is not associated with ethnicity.

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

    PubMed

    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.

  8. Proximal movements compensate for distal forelimb movement impairments in a reach-to-eat task in Huntington's disease: new insights into motor impairments in a real-world skill.

    PubMed

    Klein, Alexander; Sacrey, Lori-Ann R; Dunnett, Stephen B; Whishaw, Ian Q; Nikkhah, Guido

    2011-02-01

    Huntington's disease (HD) causes severe motor impairments that are characterized by chorea, dystonia, and impaired fine motor control. The motor deficits include deficits in the control of the forelimb, but as yet there has been no comprehensive assessment of the impairments in arm, hand and digit movements as they are used in every-day tasks. The present study investigated the reaching of twelve HD subjects and twelve age-matched control subjects on a reach-to-eat task. The subjects were asked to reach for a small food item, with the left or the right hand, and then bring it to the mouth for eating. The task assesses the major features of skilled forelimb use, including orienting to a target, transport of the hand to a target, use of a precision grasp of the target, limb withdrawal to the mouth, and release of the food item into the mouth, and the integration of the movements into a smooth act. The movements were analyzed frame-by-frame by scoring the video record using an established movement element rating scale and by biometric analysis to describe limb trajectory. All HD subjects displayed greater reliance on more proximal movements in reaching. They also displayed overall jerkiness, a significant impairment in end point error correction (i.e. no smooth trajectories), deficits in timing and terminating motion (overshooting the target), impairments in rotation of the hand, abnormalities in grasping, and impairments in releasing the food item to the mouth. Although impairment in the control of the distal segments of the limb was common to all subjects, the intrusion of choreatic movements produced a pattern of highly variable performance between subjects. The quantification of reaching performance as measured by this analysis provides new insights into the impairments of HD subjects, allows an easily administered and inexpensive way to document the many skilled limb movement abnormalities, and relates the impairments to a real-world context. The protocol can

  9. Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs.

    PubMed

    Dumkova, Jana; Vrlikova, Lucie; Vecera, Zbynek; Putnova, Barbora; Docekal, Bohumil; Mikuska, Pavel; Fictum, Petr; Hampl, Ales; Buchtova, Marcela

    2016-06-03

    The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level.

  10. Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs

    PubMed Central

    Dumkova, Jana; Vrlikova, Lucie; Vecera, Zbynek; Putnova, Barbora; Docekal, Bohumil; Mikuska, Pavel; Fictum, Petr; Hampl, Ales; Buchtova, Marcela

    2016-01-01

    The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level. PMID:27271611

  11. Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts

    PubMed Central

    Comito, Giuseppina; Segura, Coral Pons; Taddei, Maria Letizia; Lanciotti, Michele; Serni, Sergio; Morandi, Andrea; Chiarugi, Paola; Giannoni, Elisa

    2017-01-01

    Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. However, it has been recently proposed that ZA could have direct anti-tumour effects, although the molecular mechanism is unknown. We herein unravel a novel anti-tumour activity of ZA in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. Particularly, we demonstrate that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumour cells and their pro-angiogenic features. Crucially, ZA administration reverts cancer associated fibroblasts (CAFs) activation by targeting the mevalonate pathway and RhoA geranyl-geranylation, thereby impairing smooth muscle actin-α fibers organization, a prerequisite of fibroblast activation. Moreover, ZA prevents the M2 macrophages-mediated activation of normal fibroblast, highlighting the broad efficacy of this drug on tumour microenvironment. These results are confirmed in a metastatic xenograft PCa mouse model in which ZA-induced stromal normalization impairs cancer-stromal cells crosstalk, resulting in a significant reduction of primary tumour growth and metastases. Overall these findings reinforce the efficacy of ZA as a potential therapeutic approach to reduce cancer aggressiveness, by abrogating the supportive role of tumour microenvironment. PMID:27223431

  12. Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice

    PubMed Central

    Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.

    2013-01-01

    Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma. PMID:23626707

  13. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

    PubMed

    Kourtis, Iraklis C; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A; Swartz, Melody A

    2013-01-01

    Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

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

    PubMed

    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).

  15. The brain is a target organ after acute exposure to depleted uranium.

    PubMed

    Lestaevel, P; Houpert, P; Bussy, C; Dhieux, B; Gourmelon, P; Paquet, F

    2005-09-01

    The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144+/-10 microg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 microg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70+/-8 microg DU kg-1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed.

  16. SCFSAP controls organ size by targeting PPD proteins for degradation in Arabidopsis thaliana

    PubMed Central

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

    2016-01-01

    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. PMID:27048938

  17. A pointing facilitation system for motor-impaired users combining polynomial smoothing and time-weighted gradient target prediction models.

    PubMed

    Blow, Nikolaus; Biswas, Pradipta

    2017-01-01

    As computers become more and more essential for everyday life, people who cannot use them are missing out on an important tool. The predominant method of interaction with a screen is a mouse, and difficulty in using a mouse can be a huge obstacle for people who would otherwise gain great value from using a computer. If mouse pointing were to be made easier, then a large number of users may be able to begin using a computer efficiently where they may previously have been unable to. The present article aimed to improve pointing speeds for people with arm or hand impairments. The authors investigated different smoothing and prediction models on a stored data set involving 25 people, and the best of these algorithms were chosen. A web-based prototype was developed combining a polynomial smoothing algorithm with a time-weighted gradient target prediction model. The adapted interface gave an average improvement of 13.5% in target selection times in a 10-person study of representative users of the system. A demonstration video of the system is available at https://youtu.be/sAzbrKHivEY.

  18. Factors associated with cardiovascular target organ damage in children after renal transplantation.

    PubMed

    Borchert-Mörlins, Bianca; Thurn, Daniela; Schmidt, Bernhard M W; Büscher, Anja K; Oh, Jun; Kier, Tanja; Bauer, Elena; Baig, Sabrina; Kanzelmeyer, Nele; Kemper, Markus J; Büscher, Rainer; Melk, Anette

    2017-11-01

    Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study. Patients had been transplanted a mean of 5.5 (±4.0) years prior to being enrolled in the study. Anthropometric data, laboratory values and office- and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated. Cardiovascular target organ damage was determined through non-invasive measurements of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) and left ventricular mass (LVM). Elevated PWV or IMT values were detected in 22 and 58% of patients, respectively. Left ventricular hypertrophy was found in as many as 43% of patients. The prevalence of uncontrolled or untreated hypertension was 41%, of which 16% of cases were only detected by ABPM measurements. In the multivariable analysis, higher diastolic blood pressure, everolimus intake and lower estimated glomerular filtration rate were independently associated with high PWV. Higher systolic blood pressure and body mass index were associated with elevated LVM. Our results showed an alarming burden of cardiovascular subclinical organ damage in children after RT. Hypertension, obesity, immunosuppressive regimen and renal function emerged as independent risk factors of organ damage. Whereas the latter is not modifiable, the results of our study strongly indicate that the management of children after RT should focus on the control of blood pressure and weight.

  19. Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun.

    PubMed

    Baganz, Nicole; Horton, Rebecca; Martin, Kathryn; Holmes, Andrew; Daws, Lynette C

    2010-11-10

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with increased extracellular serotonin (5-HT) in limbic brain regions. The mechanism through which this occurs remains unclear. One way could be via HPA axis-dependent impairment of serotonin transporter (SERT) function, the high-affinity uptake mechanism for 5-HT. Consistent with this idea, we found that 5-HT clearance rate in hippocampus was dramatically reduced in mice exposed to repeated swim, a stimulus known to activate the HPA axis. However, this phenomenon also occurred in mice lacking SERT, ruling out SERT as a mechanism. The organic cation transporter 3 (OCT3) is emerging as an important regulator of brain 5-HT. Moreover, corticosterone, which is released upon HPA axis activation, blocks 5-HT uptake by OCT3. Repeated swim produced a persistent elevation in plasma corticosterone, and, consistent with prolonged blockade by corticosterone, we found that OCT3 expression and function were reduced in these mice. Importantly, this effect of repeated swim to reduce 5-HT clearance rate was corticosterone dependent, as evidenced by its absence in adrenalectomized mice, in which plasma corticosterone levels were essentially undetectable. Behaviorally, mice subjected to repeated swim spent less time immobile in the tail suspension test than control mice, but responded similarly to SERT- and norepinephrine transporter-selective antidepressants. Together, these results show that reduced 5-HT clearance following HPA axis activation is likely mediated, at least in part, by the corticosterone-sensitive OCT3, and that drugs developed to selectively target OCT3 (unlike corticosterone) may be candidates for the development of novel antidepressant medications.

  20. Perception of Temporal Order Is Impaired during the Time Course of the Attentional Blink

    ERIC Educational Resources Information Center

    Spalek, Thomas M.; Lagroix, Hayley E. P.; Yanko, Matthew R.; Di Lollo, Vincent

    2012-01-01

    Identification accuracy for the second of two target (T2) is impaired when presented shortly after the first (T1). Does this attentional blink (AB) also impair the perception of the order of presentation? In four experiments, three letter targets (T1, T2, T3) were inserted in a stream of digit distractors displayed in rapid serial visual…

  1. Domain-Specific Treatment Effects in Children with Language and/or Working Memory Impairments: A Pilot Study

    ERIC Educational Resources Information Center

    Wener, Sarah E; Archibald, Lisa MD

    2011-01-01

    This pilot study with an n-of-1 design examined whether children with a specific language impairment without working memory impairment (SLI), a specific working memory impairment without language impairment (SWMI), or mixed language and working memory impairments (L&WMI) may respond differently to treatment targeting verbal or visuospatial…

  2. 20 CFR 220.101 - Evaluation of mental impairments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... evaluating aspects of the mental impairment(s) relevant to the claimant's ability to work; and (3) Organizing... whether certain medical findings which have been found especially relevant to the ability to work are... from no limitation to a level of severity which is incompatible with the ability to perform those work...

  3. 20 CFR 220.101 - Evaluation of mental impairments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... evaluating aspects of the mental impairment(s) relevant to the claimant's ability to work; and (3) Organizing... whether certain medical findings which have been found especially relevant to the ability to work are... from no limitation to a level of severity which is incompatible with the ability to perform those work...

  4. 20 CFR 220.101 - Evaluation of mental impairments.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... evaluating aspects of the mental impairment(s) relevant to the claimant's ability to work; and (3) Organizing... whether certain medical findings which have been found especially relevant to the ability to work are... from no limitation to a level of severity which is incompatible with the ability to perform those work...

  5. Type 2 diabetes mellitus and exercise impairment.

    PubMed

    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.

  6. Non-Target Analyses of organic compounds in ice cores using HPLC-ESI-UHRMS

    NASA Astrophysics Data System (ADS)

    Zuth, Christoph; Müller-Tautges, Christina; Eichler, Anja; Schwikowski, Margit; Hoffmann, Thorsten

    2015-04-01

    To study the global climatic and environmental changes it is necessary to know the environmental and especially atmospheric conditions of the past. By analysing climate archives, such as for example ice cores, unique environmental information can be obtained. In contrast to the well-established analysis of inorganic species in ice cores, organic compounds have been analysed in ice cores to a much smaller extent. Because of current analytical limitations it has become commonplace to focus on 'total organic carbon' measurements or specific classes of organic molecules, as no analytical methods exist that can provide a broad characterization of the organic material present[1]. On the one hand, it is important to focus on already known atmospheric markers in ice cores and to quantify, where possible, in order to compare them to current conditions. On the other hand, unfortunately a wealth of information is lost when only a small fraction of the organic material is examined. However, recent developments in mass spectrometry in respect to higher mass resolution and mass accuracy enable a new approach to the analysis of complex environmental samples. The qualitative characterization of the complex mixture of water soluble organic carbon (WSOC) in the ice using high-resolution mass spectrometry allows for novel insights concerning the composition and possible sources of aerosol derived WSOC deposited at glacier sites. By performing a non-target analysis of an ice core from the Swiss Alps using previous enrichment by solid-phase extraction (SPE) and high performance liquid chromatography coupled to electrospray ionization and ultra-high resolution mass spectrometry (HPLC-ESI-UHRMS) 475 elemental formulas distributed onto 659 different peaks were detected. The elemental formulas were classified according to their elemental composition into CHO-, CHON-, CHOS-, CHONS-containing compounds and 'others'. Several methods for the analysis of complex data sets of high resolution

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

    PubMed

    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.

  8. A chemodynamic approach for estimating losses of target organic chemicals from water during sample holding time

    USGS Publications Warehouse

    Capel, P.D.; Larson, S.J.

    1995-01-01

    Minimizing the loss of target organic chemicals from environmental water samples between the time of sample collection and isolation is important to the integrity of an investigation. During this sample holding time, there is a potential for analyte loss through volatilization from the water to the headspace, sorption to the walls and cap of the sample bottle; and transformation through biotic and/or abiotic reactions. This paper presents a chemodynamic-based, generalized approach to estimate the most probable loss processes for individual target organic chemicals. The basic premise is that the investigator must know which loss process(es) are important for a particular analyte, based on its chemodynamic properties, when choosing the appropriate method(s) to prevent loss.

  9. Target organ damage and incident type 2 diabetes mellitus: the Strong Heart Study.

    PubMed

    de Simone, Giovanni; Wang, Wenyu; Best, Lyle G; Yeh, Fawn; Izzo, Raffaele; Mancusi, Costantino; Roman, Mary J; Lee, Elisa T; Howard, Barbara V; Devereux, Richard B

    2017-05-12

    Recent analyses in a registry of hypertensive patients suggested that preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis are associated with incident type 2 diabetes, independent of confounders. We assess the relation between prevalent cardio-renal target organ damage (TOD) and subsequent incident type 2 diabetes in a population-based study with high prevalence of obesity. We selected 2887 non-diabetic participants from two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA) dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable logistic regression models were used to identify variables responsible for the association between initial TODs and incident diabetes at 4-year follow-up (FU). After 4 years, 297 new cases of diabetes (10%) were identified, 216 of whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001). Participants developing type 2 diabetes exhibited higher inflammatory markers, fat-free mass and adipose mass and higher prevalence of initial LVH and LA dilatation than those without (both p < 0.04). In multivariable logistic regression, controlling for age, sex, family relatedness, presence of arterial hypertension and IFG, all three indicators of TOD predicted incident diabetes (all p < 0.01). However, the effects of TOD was offset when body fat and inflammatory markers were introduced into the model. In this population-based study with high prevalence of obesity, TOD precedes clinical appearance of type 2 diabetes and is related to the preceding metabolic status, body composition and inflammatory status. Trial registration Trial registration number: NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988.

  10. [Target and non-target screening of volatile organic compounds in industrial exhaust gas using thermal desorption-gas chromatography-mass spectrometry].

    PubMed

    Ma, Huilian; Jin, Jing; Li, Yun; Chen, Jiping

    2017-10-08

    A method of comprehensive screening of the target and non-target volatile organic compounds (VOCs) in industrial exhaust gas using thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) has been developed. In this paper, two types of solid phase adsorption column were compared, and the Tenex SS TD Tube was selected. The analytes were enriched into the adsorption tube by constant flow sampling, and detected by TD-GC-MS in full scan mode. Target compounds were quantified by internal standard method, and the quantities of non-target compounds were calculated by response coefficient of toluene. The method detection limits (MDLs) for the 24 VOCs were 1.06 to 5.44 ng, and MDLs could also be expressed as 0.004 to 0.018 mg/m 3 assuming that the sampling volume was 300 mL. The average recoveries were in the range of 78.4% to 89.4% with the relative standard deviations (RSDs) of 3.9% to 14.4% ( n =7). The established analytical method was applied for the comprehensive screening of VOCs in a waste incineration power plant in Dalian city. Twenty-nine VOCs were identified. In these compounds, only five VOCs were the target compounds set in advance, which accounted for 26.7% of the total VOCs identified. Therefore, this study further proved the importance of screening non-target compounds in the analysis of VOCs in industrial exhaust gas, and has certain reference significance for the complete determination of VOCs distribution.

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

    EPA Science Inventory

    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...

  12. Does the achievement of an intermediate glycemic target reduce organ failure and mortality? A post hoc analysis of the Glucontrol trial.

    PubMed

    Penning, Sophie; Chase, J Geoffrey; Preiser, Jean-Charles; Pretty, Christopher G; Signal, Matthew; Mélot, Christian; Desaive, Thomas

    2014-06-01

    This research evaluates the impact of the achievement of an intermediate target glycemic band on the severity of organ failure and mortality. Daily Sequential Organ Failure Assessment (SOFA) score and the cumulative time in a 4.0 to 7.0 mmol/L band (cTIB) were evaluated daily up to 14 days in 704 participants of the multicentre Glucontrol trial (16 centers) that randomized patients to intensive group A (blood glucose [BG] target: 4.4-6.1 mmol/L) or conventional group B (BG target: 7.8-10.0 mmol/L). Sequential Organ Failure Assessment evolution was measured by percentage of patients with SOFA less than or equal to 5 on each day, percentage of individual organ failures, and percentage of organ failure-free days. Conditional and joint probability analysis of SOFA and cTIB 0.5 or more assessed the impact of achieving 4.0 to 7.0 mmol/L target glycemic range on organ failure. Odds ratios (OR) compare the odds risk of death for cTIB 0.5 or more vs cTIB less than 0.5, where a ratio greater than 1.0 indicates an improvement for achieving cTIB 0.5 or more independent of SOFA or glycemic target. Groups A and B were matched for demographic and severity of illness data. Blood glucose differed between groups A and B (P<.05), as expected. There was no difference in the percentage of patients with SOFA less than or equal to 5, individual organ failures, and organ failure-free days between groups A and B over days 1 to 14. However, 20% to 30% of group A patients failed to achieve cTIB 0.5 or more for all days, and significant crossover confounds interpretation. Mortality OR was greater than 1.0 for patients with cTIB 0.5 or more in both groups but much higher for group A on all days. There was no difference in organ failure in the Glucontrol study based on intention to treat to different glycemic targets. Actual outcomes and significant crossover indicate that this result may not be due to the difference in target or treatment. Odds ratios-associated achieving an intermediate 4

  13. Functional Impairment and Hospital Readmission in Medicare Seniors

    PubMed Central

    Greysen, S. Ryan; Cenzer, Irena Stijacic; Auerbach, Andrew D.; Covinsky, Kenneth E.

    2015-01-01

    patients admitted with conditions targeted by Medicare (heart failure, myocardial infarction, and pneumonia) revealed a parallel trend with larger effects for the most-impaired (16.9% readmission rate for no impairment vs. 25.7% for dependency in ≥3 ADLs, OR 1.70; 1.04–2.78). Conclusions Functional impairment is associated with increased risk of 30-day, all-cause hospital readmission in Medicare seniors, especially those admitted for heart failure, myocardial infarction or pneumonia. Functional impairment on admission may be an overlooked but highly suitable target for interventions to reduce Medicare hospital readmissions. Relevance Functional impairment may be an important but under-addressed factor in preventing readmissions for Medicare seniors. PMID:25642907

  14. Resources for the Visually Impaired.

    ERIC Educational Resources Information Center

    Oseroff, Andrew; And Others

    1987-01-01

    Suggestions for resource room teachers working with visually impaired learning disabled students include: consideration of students' unique learning needs; assessment of functional vision; use of assistive devices (such as closed-circuit television); classroom arrangement that facilitates organization and movement; and basic skills instruction…

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

    PubMed

    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.

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

    PubMed Central

    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.

    2015-01-01

    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 earlier in vitro. The Transforming Growth Factor beta (TGFβ)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. PMID:26187706

  17. Piracetam treatment in patients with cognitive impairment.

    PubMed

    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.

  18. Music Therapy for the Visually Impaired.

    ERIC Educational Resources Information Center

    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)

  19. Movement System Impairment-Guided Approach to the Physical Therapist Treatment of a Patient With Postpartum Pelvic Organ Prolapse and Mixed Urinary Incontinence: Case Report.

    PubMed

    Kurz, Jenny; Borello-France, Diane

    2017-04-01

    Women with postpartum pelvic organ prolapse (POP) and urinary incontinence are often treated by physical therapists specializing in women's health. Movement system impairments often coexist in this patient population. The purpose of this case report is to describe the physical therapist treatment of a woman with postpartum POP complicated by additional pelvic symptoms. A 31-year-old woman presented with postpartum POP, diastasis recti, urinary incontinence, and constipation. Movement system impairments were consistent with a physical therapist diagnosis of femoral adduction-medial rotation syndrome exacerbated by levator ani muscle weakness and incoordination and impaired intra-abdominal pressure regulation. Interventions, based on a movement system guided approach, included postural correction; pelvic-floor, abdominal, and hip muscle strengthening; functional training to correct identified movement faults; and patient education. Movement system impairment outcomes included: correction of femoral adduction-medial rotation and knee hyperextension during standing at rest, ambulation, and exercise; increased hip muscle strength; and effective regulation of intra-abdominal pressure (resolution of breath holding with the Valsalva maneuver) during all transitional movements and therapeutic exercise. The patient also demonstrated reductions in POP, urinary, and colorectal symptom severity that exceeded the minimal clinically important difference. Additionally, she demonstrated a reduction in diastasis rectus distance. A movement system impairment-guided approach led the physical therapist to consider impairments outside the pelvic floor that could have contributed to the patient's pelvic symptoms. Using this approach, the patient achieved resolution of musculoskeletal and movement impairments and reductions in POP, urinary and colorectal symptoms, and symptom-related distress. © 2016 American Physical Therapy Association

  20. Verbal and Visual Memory Impairments in Bipolar I and II Disorder.

    PubMed

    Ha, Tae Hyon; Kim, Ji Sun; Chang, Jae Seung; Oh, Sung Hee; Her, Ju Young; Cho, Hyun Sang; Park, Tae Sung; Shin, Soon Young; Ha, Kyooseob

    2012-12-01

    To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies. Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis. Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant. Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments.

  1. Vision In Stroke cohort: Profile overview of visual impairment.

    PubMed

    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 <0.3 logMAR and 13.5% <0.5 logMAR. Acquired strabismus was noted in 16% and acquired ocular motility disorders in 68%. Peripheral 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.

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

    PubMed Central

    Cichocki, Joseph A.; Guyton, Kathryn Z.; Guha, Neela; Chiu, Weihsueh A.

    2016-01-01

    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. PMID:27511820

  3. Can eHealth tools enable health organizations to reach their target audience?

    PubMed

    Zbib, Ahmad; Hodgson, Corinne; Calderwood, Sarah

    2011-01-01

    Data from the health risk assessment operated by the Heart and Stroke Foundation found users were more likely to be female; married; have completed post secondary education; and report hypertension, stroke, or being overweight or obese. In developing and operating eHealth tools for health promotion, organizations should compare users to their target population(s). eHealth tools may not be optimal for reaching some higher-risk sub-groups, and a range of social marketing approaches may be required.

  4. Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

    PubMed

    Yang, Ye; Zhang, Jianyun; Yao, Yijun

    2017-01-01

    Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

  5. Does remembering emotional items impair recall of same-emotion items?

    PubMed

    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.

  6. Lost Forever or Temporarily Misplaced? The Long Debate about the Nature of Memory Impairment

    ERIC Educational Resources Information Center

    Squire, Larry R.

    2006-01-01

    Studies of memory impairment in humans and experimental animals have been fundamental to learning about the organization of memory and its cellular and molecular substrates. When memory impairment occurs, especially after perturbations of the nervous system, the question inevitably arises whether the impairment reflects impaired information…

  7. Hypertension Severity Is Associated With Impaired Cognitive Performance.

    PubMed

    Muela, Henrique C S; Costa-Hong, Valeria A; Yassuda, Mônica S; Moraes, Natália C; Memória, Claudia M; Machado, Michel F; Macedo, Thiago A; Shu, Edson B S; Massaro, Ayrton R; Nitrini, Ricardo; Mansur, Alfredo J; Bortolotto, Luiz A

    2017-01-11

    Most evidence of target-organ damage in hypertension (HTN) is related to the kidneys and heart. Cerebrovascular and cognitive impairment are less well studied. Therefore, this study analyzed changes in cognitive function in patients with different stages of hypertension compared to nonhypertensive controls. In a cross-sectional study, 221 (71 normotensive and 150 hypertensive) patients were compared. Patients with hypertension were divided into 2 stages according to blood pressure (BP) levels or medication use (HTN-1: BP, 140-159/90-99 or use of 1 or 2 antihypertensive drugs; HTN-2: BP, ≥160/100 or use of ≥3 drugs). Three groups were comparatively analyzed: normotension, HTN stage 1, and HTN stage 2. The Mini-Mental State Examination, Montreal Cognitive Assessment, and a validated comprehensive battery of neuropsychological tests that assessed 6 main cognitive domains were used to determine cognitive function. Compared to the normotension and HTN stage-1, the severe HTN group had worse cognitive performance based on Mini-Mental State Examination (26.8±2.1 vs 27.4±2.1 vs 28.0±2.0; P=0.004) or Montreal Cognitive Assessment (23.4±3.7 vs 24.9±2.8 vs 25.5±3.2; P<0.001). On the neuropsychological tests, patients with hypertension had worse performance in language, processing speed, visuospatial abilities, and memory. Age, hypertension stage, and educational level were the best predictors of cognitive impairment in patients with hypertension in different cognitive domains. Cognitive impairment was more frequent in patients with hypertension, and this was related to hypertension severity. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Emerging Roles for MicroRNAs in Diabetic Microvascular Disease: Novel Targets for Therapy

    PubMed Central

    Zhang, Yu; Sun, Xinghui; Icli, Basak

    2017-01-01

    Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs (miRNAs), noncoding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury. We highlight current pathophysiological paradigms of miRNAs and their targets involved in regulating the diabetic microvasculature in a range of diabetes-associated complications such as retinopathy, nephropathy, wound healing, and myocardial injury. We provide an update of the potential use of circulating miRNAs diagnostically in type I or type II diabetes. Finally, we discuss emerging delivery platforms for manipulating miRNA expression or function as the next frontier in therapeutic intervention to improve diabetes-associated microvascular dysfunction and its attendant clinical consequences. PMID:28323921

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

    PubMed

    Ehret, Georg B; Ferreira, Teresa; 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

    2016-10-01

    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-associated loci, of which 17 were new; 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 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.

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

    PubMed Central

    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

  11. Targeting nursing homes under the Quality Improvement Organization program's 9th statement of work.

    PubMed

    Stevenson, David G; Mor, Vincent

    2009-09-01

    In the Quality Improvement Organization (QIO) program's latest Statement of Work, the Centers for Medicare and Medicaid Services (CMS) is targeting its nursing home activities toward facilities that perform poorly on two quality measures-pressure ulcers and restraint use. The designation of target facilities is a shift in strategy for CMS and a direct response to criticism that QIO program resources were not being targeted effectively to facilities or clinical areas that most needed improvement. Using administrative data, this article analyzes implications of using narrowly defined criteria to identify facilities that need improvement, particularly in light of considerable evidence showing that nursing home quality is multidimensional and may change over time. The analyses show that one in four facilities is targeted for improvement nationally but that approximately half of some states' facilities are targeted while other states have almost none targeted. The analyses also convey deeper limitations to using threshold values on individual measures to identify poorly performing homes. Target facilities can be among the top performers on a range of other quality measures, and their performance on targeted measures themselves may change over time. The implication of these features is that a very different group of facilities would have been chosen had the QIO program targeted other measures or examined performance at a different point in time. Ultimately, CMS has chosen a blunt instrument to identify poorly performing nursing homes, and supplemental strategies-such as soliciting input from state survey agencies and more closely aligning quality improvement and quality assurance efforts-should be considered to address potential limitations.

  12. [Cognitive impairments accompanying the burnout syndrome - a review].

    PubMed

    Riedrich, Karin; Weiss, Elisabeth M; Dalkner, Nina; Reininghaus, Eva; Papousek, Ilona; Schwerdtfeger, Andreas; Lackner, Helmut K; Reininghaus, Bernd

    2017-03-01

    The rising prevalence of the burnout syndrome has increasingly moved it into the focus of scientific interest. In addition to emotional exhaustion and depersonalization, particularly reduced personal accomplishment has strong societal and economic effects. In recent years reduced personal accomplishment has increasingly been linked to cognitive impairment. However, up to now only a few studies have objectively assessed cognitive deficits in burnout patients. This article gives an overview of 16 studies which examined cognitive abilities in burnout patients. The findings are partly contradictory, probably due to methodical differences. Consensus has emerged concerning impairments of executive functions, i.a. vigilance, and memory updating and monitoring. Multifactorial causation may underlie the cognitive impairments. Targeted longitudinal studies are necessary in order to identify the affected cognitive functions and be able to make causal inferences on links between the burnout syndrome and specific cognitive impairments.

  13. EFFECT OF NON-TARGET ORGANICS ON ORGANIC CHEMICAL TRANSPORT

    EPA Science Inventory

    To improve our standard of living, man has synthesized organic compounds for use in products considered essential for life. These compounds are having and will continue to have a significant impact on the terrestrial environment. Understanding organic chemical transport through s...

  14. The role of executive functions in social impairment in Autism Spectrum Disorder.

    PubMed

    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.

  15. The limits of arousal's memory-impairing effects on nearby information.

    PubMed

    Mather, Mara; Gorlick, Marissa A; Nesmith, Kathryn

    2009-01-01

    Showing an arousing central stimulus in a scene often leads to enhanced memory for the arousing central information and impaired memory for peripheral details. However, it is not clear from previous work whether arousing stimuli impair memory for all nonarousing nearby information or just background information. In several experiments, we tested how emotionally arousing pictures affect memory for nearby pictures and for background information. We found that when 2 pictures were presented together, an arousing picture did not affect item and location memory for the other picture. In contrast, an arousing picture impaired memory for a background pattern. These findings suggest that arousal impairs memory for information that is the target of perceptual suppression, such as background information when there is a figure-ground distinction, but does not impair memory for other foreground information.

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    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.

  18. Tracking targeted bimodal nanovaccines: immune responses and routing in cells, tissue, and whole organism.

    PubMed

    Cruz, Luis J; Tacken, Paul J; Zeelenberg, Ingrid S; Srinivas, Mangala; Bonetto, Fernando; Weigelin, Bettina; Eich, Christina; de Vries, I Jolanda; Figdor, Carl G

    2014-12-01

    Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs), involved in the induction of immunity and currently exploited for antitumor immunotherapies. An optimized noninvasive imaging modality capable of determining and quantifying DC-targeted nanoparticle (NP) trajectories could provide valuable information regarding therapeutic vaccine outcome. Here, targeted poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) recognizing DC receptors were equipped with superparamagnetic iron oxide particles (SPIO) or gold nanoparticles with fluorescently labeled antigen. The fluorescent label allowed for rapid analysis and quantification of DC-specific uptake of targeted PLGA NPs in comparison to uptake by other cells. Transmission electron microscopy (TEM) showed that a fraction of the encapsulated antigen reached the lysosomal compartment of DCs, where SPIO and gold were already partially released. However, part of the PLGA NPs localized within the cytoplasm, as confirmed by confocal microscopy. DCs targeted with NPs carrying SPIO or fluorescent antigen were detected within lymph nodes as early as 1 h after injection by magnetic resonance imaging (MRI). Despite the fact that targeting did not markedly affect PLGA NP biodistribution on organism and tissue level, it increased delivery of NPs to DCs residing in peripheral lymph nodes and resulted in enhanced T cell proliferation. In conclusion, two imaging agents within a single carrier allows tracking of targeted PLGA NPs at the subcellular, cellular, and organismal levels, thereby facilitating the rational design of in vivo targeted vaccination strategies.

  19. Cue-independent memory impairment by reactivation-coupled interference in human declarative memory.

    PubMed

    Zhu, Zijian; Wang, Yingying; Cao, Zhijun; Chen, Biqing; Cai, Huaqian; Wu, Yanhong; Rao, Yi

    2016-10-01

    Memory is a dynamic process. While memory becomes increasingly resistant to interference after consolidation, a brief reactivation renders it unstable again. Previous studies have shown that interference, when applied upon reactivation, impairs the consolidated memory, presumably by disrupting the reconsolidation of the memory. However, attempts have failed in disrupting human declarative memory, raising a question about whether declarative memory becomes unstable upon reactivation. Here, we used a double-cue/one-target paradigm, which associated the same target with two different cues in initial memory formation. Only one cue/target association was later reactivated and treated with behavioral interference. Our results showed, for the first time, that reactivation-coupled interference caused cue-independent memory impairment that generalized to other cues associated with the memory. Critically, such memory impairment appeared immediately after interference, before the reconsolidation process was completed, suggesting that common manipulations of reactivation-coupled interference procedures might disrupt other processes in addition to the reconsolidation process in human declarative memory. Copyright © 2016. Published by Elsevier B.V.

  20. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice

    PubMed Central

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Martinez, Ana; Faghihi, Mohammad A.; Jope, Richard S.; Beurel, Eleonore

    2017-01-01

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA– or HDAC4 siRNA–induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1–/– mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets. PMID:28352664

  1. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

    PubMed

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Eldar-Finkelman, Hagit; Martinez, Ana; Faghihi, Mohammad A; Jope, Richard S; Beurel, Eleonore

    2017-03-23

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1 -/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.

  2. Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.

    PubMed

    Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel

    2014-07-15

    Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.

  3. Synthetic lipid nanoparticles targeting steroid organs.

    PubMed

    Mérian, Juliette; Boisgard, Raphaël; Decleves, Xavier; Thezé, Benoît; Texier, Isabelle; Tavitian, Bertrand

    2013-11-01

    Lipidots are original nanoparticulate 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 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine 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 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine. 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 nanometric size and composition, conferring on them a lipoproteinlike behavior. The affinity of lipidots for steroid hormone-rich areas is of interest to address drugs and contrast agents to lipoprotein-receptor-overexpressing cancer cells found in hormone-dependent tumors.

  4. The limits of arousal's memory impairing effects on nearby information

    PubMed Central

    Mather, Mara; Gorlick, Marissa; Nesmith, Kathryn

    2009-01-01

    Showing an arousing central stimulus in a scene often leads to enhanced memory for the arousing central information and impaired memory for peripheral details. However, it is not clear from previous work whether arousing stimuli impair memory for all non-arousing nearby information or just background information. In several experiments, we tested how emotionally arousing pictures affect memory for nearby pictures and for background information. We found that when two pictures were presented together, having one of the pictures be arousing did not affect item and location memory for the other picture. In contrast, an arousing picture impaired memory for a background pattern. These findings suggest that arousal impairs memory for information that is the target of perceptual suppression, such as background information when there is a figure-ground distinction, but does not impair memory for other foreground information. PMID:19827704

  5. [Prevalence of target organ damage in patients treated for primary arterial hypertension: Comparison between men and women. ESSENTIELLE study].

    PubMed

    Boivin, J-M; Koch, C; Vigié, L; Meppiel, L

    2015-06-01

    To compare the percentages of men and women treated for primary arterial hypertension presenting with at least one target organ damage; to identify factors associated with target organ damage and/or blood pressure control. Observational, transverse study carried out between March 2012 and July 2013 on a representative sample of 2666 outpatients (including 1343 men) consulting general practitioners (n=469) or cardiologists (n=250) in routine follow-up. Characteristics "men vs. women" were: mean age (62.6 ± 11.6 vs. 57.4 ± 14.7 years; P<0.0001); ≥ 60 years (61.1% vs. 43.9%; P<0.0001); waist circumference (98.9 ± 12.2 vs. 89.4 ± 14.3 cm; P<0.0001); SBP (146.5 ± 16.1 vs. 145.8 ± 17.0 mmHg; NS); DBP (85.1 ± 10.3 vs. 84.2 ± 10.4; P=0,03). Target organ damage was more frequent in men (37.6% vs. 22.9%; P<0.0001), whether it was subclinical (20.4% vs. 13.6%; P<0.0001) or documented (26.3% vs. 13.5%; P<0.0001); some patients presented with both types of damages. Men developed more often microalbuminuria (6.5% vs. 4.3%; P=0.01) and LVH (16.3% vs. 10.5%; P<0.0001); some patients presented with both types of subclinical injuries. Target organ damage was more common in men without regular physical activity than in those exercising regularly (42.1% vs. 32.5%; P=0.0004). Regular exercises had no effect in women (24.1% vs. 21.3%). For both sexes, other factors associated with target organ damage were: age ≥ 60 years, myocardial infarction/sudden death in family history, LDL-cholesterol ≥ 1.60 g/L, HDL-cholesterol ≤ 0.40 g/L. Stroke before 45 years in family history was a predictive factor in women. Hypertension was controlled in one third of patients without difference between sexes. In women, hypertension was less often controlled in case of excessive alcohol consumption compared to normal alcohol intake (17.9% vs. 36.1%; P=0.0007); this factor had no effect in men (28.1% vs. 32.6%). Other factors associated with poor blood pressure control were: BMI (P=0.002), LDL

  6. Enhanced guide-RNA design and targeting analysis for precise CRISPR genome editing of single and consortia of industrially relevant and non-model organisms.

    PubMed

    Mendoza, Brian J; Trinh, Cong T

    2018-01-01

    Genetic diversity of non-model organisms offers a repertoire of unique phenotypic features for exploration and cultivation for synthetic biology and metabolic engineering applications. To realize this enormous potential, it is critical to have an efficient genome editing tool for rapid strain engineering of these organisms to perform novel programmed functions. To accommodate the use of CRISPR/Cas systems for genome editing across organisms, we have developed a novel method, named CRISPR Associated Software for Pathway Engineering and Research (CASPER), for identifying on- and off-targets with enhanced predictability coupled with an analysis of non-unique (repeated) targets to assist in editing any organism with various endonucleases. Utilizing CASPER, we demonstrated a modest 2.4% and significant 30.2% improvement (F-test, P < 0.05) over the conventional methods for predicting on- and off-target activities, respectively. Further we used CASPER to develop novel applications in genome editing: multitargeting analysis (i.e. simultaneous multiple-site modification on a target genome with a sole guide-RNA requirement) and multispecies population analysis (i.e. guide-RNA design for genome editing across a consortium of organisms). Our analysis on a selection of industrially relevant organisms revealed a number of non-unique target sites associated with genes and transposable elements that can be used as potential sites for multitargeting. The analysis also identified shared and unshared targets that enable genome editing of single or multiple genomes in a consortium of interest. We envision CASPER as a useful platform to enhance the precise CRISPR genome editing for metabolic engineering and synthetic biology applications. https://github.com/TrinhLab/CASPER. ctrinh@utk.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  7. Emotion Causes Targeted Forgetting of Established Memories

    PubMed Central

    Strange, Bryan A.; Kroes, Marijn C. W.; Fan, Judith E.; Dolan, Raymond J.

    2010-01-01

    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 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval. PMID:21191439

  8. Emotion causes targeted forgetting of established memories.

    PubMed

    Strange, Bryan A; Kroes, Marijn C W; Fan, Judith E; Dolan, Raymond J

    2010-01-01

    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 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval.

  9. Impaired Contingent Attentional Capture Predicts Reduced Working Memory Capacity in Schizophrenia

    PubMed Central

    Mayer, Jutta S.; Fukuda, Keisuke; Vogel, Edward K.; Park, Sohee

    2012-01-01

    Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding. PMID:23152783

  10. Impaired contingent attentional capture predicts reduced working memory capacity in schizophrenia.

    PubMed

    Mayer, Jutta S; Fukuda, Keisuke; Vogel, Edward K; Park, Sohee

    2012-01-01

    Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding.

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

    PubMed

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

    2017-09-29

    . Targeted nanobubbles carrying CAIX 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.

  12. Relationships Between Divided Attention and Working Memory Impairment in People With Schizophrenia

    PubMed Central

    Gray, Bradley E.; Hahn, Britta; Robinson, Benjamin; Harvey, Alex; Leonard, Carly J.; Luck, Steven J.; Gold, James M.

    2014-01-01

    Recent studies suggest that people with schizophrenia (PSZ) have difficulty distributing their attention broadly. Other research suggests that PSZ have reduced working memory (WM) capacity. This study tested whether these findings reflect a common underlying deficit. We measured the ability to distribute attention by means of the Useful Field of View (UFOV) task, in which participants must distribute attention so that they can discriminate a foveal target and simultaneously localize a peripheral target. Participants included 50 PSZ and 52 healthy control subjects. We found that PSZ exhibited severe impairments in UFOV performance, that UFOV performance was highly correlated with WM capacity in PSZ (r = −.61), and that UFOV impairments could not be explained by either impaired low-level processing or a generalized deficit. These results suggest that a common mechanism explains deficits in the ability to distribute attention broadly, reduced WM capacity, and other aspects of impaired cognition in schizophrenia. We hypothesize that this mechanism may involve abnormal local circuit dynamics that cause a hyperfocusing of resources onto a small number of internal representations. PMID:24748559

  13. Detection of memory impairment in a community-based system: a collaborative study.

    PubMed

    Kiral, Kahraman; Ozge, Aynur; Sungur, Mehmet Ali; Tasdelen, Bahar

    2013-05-01

    The ability to distinguish between older people with cognitive impairment and those who age in a healthy manner is crucial because cognitive impairment may be a precursor to full-blown dementia. Therefore, an early diagnosis of cognitive impairment is important. However, patients are often admitted to a hospital only when they already have a serious cognitive impairment. Consequently, cooperative studies between clinics and community-based organizations may assist hospitals in detecting early cognitive impairment. This article examines how community-based organizations can contribute to the early diagnosis of dementia. A cooperation model between the Neurology Department of Mersin University Hospital and the Mersin branch of the Alzheimer's Association was developed. Trained professionals used a neuropsychological battery to evaluate 50 individuals at the Mersin branch of the Alzheimer's Association in Turkey. Individuals whose performance fell below the average (1 standard deviation or less) were subsequently referred to the hospital. On the basis of the neurological and neuropsychological assessments, 11 participants were placed in the mild cognitive impairment group and 39 were placed in the healthy group. The results suggest that the Standardized Mini-Mental State Examination and the Three Words-Three Shapes Test are useful tools for detecting early memory impairments in a community-based setting.

  14. Visual search performance among persons with schizophrenia as a function of target eccentricity.

    PubMed

    Elahipanah, Ava; Christensen, Bruce K; Reingold, Eyal M

    2010-03-01

    The current study investigated one possible mechanism of impaired visual attention among patients with schizophrenia: a reduced visual span. Visual span is the region of the visual field from which one can extract information during a single eye fixation. This study hypothesized that schizophrenia-related visual search impairment is mediated, in part, by a smaller visual span. To test this hypothesis, 23 patients with schizophrenia and 22 healthy controls completed a visual search task where the target was pseudorandomly presented at different distances from the center of the display. Response times were analyzed as a function of search condition (feature vs. conjunctive), display size, and target eccentricity. Consistent with previous reports, patient search times were more adversely affected as the number of search items increased in the conjunctive search condition. It was important however, that patients' conjunctive search times were also impacted to a greater degree by target eccentricity. Moreover, a significant impairment in patients' visual search performance was only evident when targets were more eccentric and their performance was more similar to healthy controls when the target was located closer to the center of the search display. These results support the hypothesis that a narrower visual span may underlie impaired visual search performance among patients with schizophrenia. Copyright 2010 APA, all rights reserved

  15. Intercepting a moving target: On-line or model-based control?

    PubMed

    Zhao, Huaiyong; Warren, William H

    2017-05-01

    When walking to intercept a moving target, people take an interception path that appears to anticipate the target's trajectory. According to the constant bearing strategy, the observer holds the bearing direction of the target constant based on current visual information, consistent with on-line control. Alternatively, the interception path might be based on an internal model of the target's motion, known as model-based control. To investigate these two accounts, participants walked to intercept a moving target in a virtual environment. We degraded the target's visibility by blurring the target to varying degrees in the midst of a trial, in order to influence its perceived speed and position. Reduced levels of visibility progressively impaired interception accuracy and precision; total occlusion impaired performance most and yielded nonadaptive heading adjustments. Thus, performance strongly depended on current visual information and deteriorated qualitatively when it was withdrawn. The results imply that locomotor interception is normally guided by current information rather than an internal model of target motion, consistent with on-line control.

  16. Blindness and visual impairment in opera.

    PubMed

    Aydin, Pinar; Ritch, Robert; O'Dwyer, John

    2018-01-01

    The performing arts mirror the human condition. This study sought to analyze the reasons for inclusion of visually impaired characters in opera, the cause of the blindness or near blindness, and the dramatic purpose of the blindness in the storyline. We reviewed operas from the 18 th century to 2010 and included all characters with ocular problems. We classified the cause of each character's ocular problem (organic, nonorganic, and other) in relation to the thematic setting of the opera: biblical and mythical, blind beggars or blind musicians, historical (real or fictional characters), and contemporary or futuristic. Cases of blindness in 55 characters (2 as a choir) from 38 operas were detected over 3 centuries of repertoire: 11 had trauma-related visual impairment, 5 had congenital blindness, 18 had visual impairment of unknown cause, 9 had psychogenic or malingering blindness, and 12 were symbolic or miracle-related. One opera featured an ophthalmologist curing a patient. The research illustrates that visual impairment was frequently used as an artistic device to enhance the intent and situate an opera in its time.

  17. Auditory and visual orienting responses in listeners with and without hearing-impairment

    PubMed Central

    Brimijoin, W. Owen; McShefferty, David; Akeroyd, Michael A.

    2015-01-01

    Head movements are intimately involved in sound localization and may provide information that could aid an impaired auditory system. Using an infrared camera system, head position and orientation was measured for 17 normal-hearing and 14 hearing-impaired listeners seated at the center of a ring of loudspeakers. Listeners were asked to orient their heads as quickly as was comfortable toward a sequence of visual targets, or were blindfolded and asked to orient toward a sequence of loudspeakers playing a short sentence. To attempt to elicit natural orienting responses, listeners were not asked to reorient their heads to the 0° loudspeaker between trials. The results demonstrate that hearing-impairment is associated with several changes in orienting responses. Hearing-impaired listeners showed a larger difference in auditory versus visual fixation position and a substantial increase in initial and fixation latency for auditory targets. Peak velocity reached roughly 140 degrees per second in both groups, corresponding to a rate of change of approximately 1 microsecond of interaural time difference per millisecond of time. Most notably, hearing-impairment was associated with a large change in the complexity of the movement, changing from smooth sigmoidal trajectories to ones characterized by abruptly-changing velocities, directional reversals, and frequent fixation angle corrections. PMID:20550266

  18. Exploring What’s Missing: What Do Target Absent Trials Reveal About Autism Search Superiority?

    PubMed Central

    Keehn, Brandon; Joseph, Robert M.

    2016-01-01

    We used eye-tracking to investigate the roles of enhanced discrimination and peripheral selection in superior visual search in autism spectrum disorder (ASD). Children with ASD were faster at visual search than their typically developing peers. However, group differences in performance and eye-movements did not vary with the level of difficulty of discrimination or selection. Rather, consistent with prior ASD research, group differences were mainly the effect of faster performance on target-absent trials. Eye-tracking revealed a lack of left-visual-field search asymmetry in ASD, which may confer an additional advantage when the target is absent. Lastly, ASD symptomatology was positively associated with search superiority, the mechanisms of which may shed light on the atypical brain organization that underlies social-communicative impairment in ASD. PMID:26762114

  19. Mild cognitive impairment (MCI) - the novel trend of targeting Alzheimer's disease in its early stages - methodological considerations.

    PubMed

    Pater, C

    2011-11-01

    While much uncertainty exists in the estimates of the global burden of Alzheimer's disease and about the potential impact of various interventions, there is a widespread acceptance of the fact that the steady increase in the incidence and prevalence of the condition worldwide is becoming a massive public health problem as well as a huge economic burden for all healthcare systems and societies. These heavy demands are further compounded by the poor quality of life of the affected individuals, of their families and of their caregivers. The epidemic proportion of Alzheimer's disease has triggered relentless attempts for development of treatment approaches during the past two decades by a multitude of pharmaceuticals and biotech companies. Commercial development of the acetylcholinesterase inhibitors has, until recently, virtually dominated the field and, although efficacy has been demonstrated for five different products, the longterm clinical results suggested that alternate approaches were warranted. Disease modifying strategies targeting the β- amyloid plaques (e.g., decreasing β-amyloid formation through β- and γ-secretase inhibition, diminishing β-amyloid aggregation through anti-aggregants or enhancement of β-amyloid clearance through active/passive immunization), targeting the neurofibrillary tangles through inhibition of tau protein hyperphosphorilation or, more recently, by increasing mitochondrial permeability, all these potential treatment modalities are facing major methodological challenges during the conduct of a myriad of clinical trials meant to bring the novel therapies to the market. Failure of more than 400 products tested in more than 800 clinical trials to date, with many of these failures occurring in late stage development (phase III) have triggered a paradigm shift toward targeting of the early stages of cognitive deficiencies (mild cognitive impairment- MCI) and a refinement of the investigative methodologies. The great heterogeneity of

  20. MiR-137 Targets Estrogen-Related Receptor Alpha and Impairs the Proliferative and Migratory Capacity of Breast Cancer Cells

    PubMed Central

    Zhao, Yuanyin; Li, Yuping; Lou, Guiyu; Zhao, Li; Xu, Zhizhen; Zhang, Yan; He, Fengtian

    2012-01-01

    ERRα is an orphan nuclear receptor emerging as a novel biomarker of breast cancer. Over-expression of ERRα in breast tumor is considered as a prognostic factor of poor clinical outcome. The mechanisms underlying the dysexpression of this nuclear receptor, however, are poorly understood. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. In the present study, we have identified that the expression of ERRα is regulated by miR-137, a potential tumor suppressor microRNA. The bioinformatics search revealed two putative and highly conserved target-sites for miR-137 located within the ERRα 3′UTR at nt 480–486 and nt 596–602 respectively. Luciferase-reporter assay demonstrated that the two predicted target sites were authentically functional. They mediated the repression of reporter gene expression induced by miR-137 in an additive manner. Moreover, ectopic expression of miR-137 down-regulated ERRα expression at both protein level and mRNA level, and the miR-137 induced ERRα-knockdown contributed to the impaired proliferative and migratory capacity of breast cancer cells. Furthermore, transfection with miR-137mimics suppressed at least two downstream target genes of ERRα–CCNE1 and WNT11, which are important effectors of ERRα implicated in tumor proliferation and migration. Taken together, our results establish a role of miR-137 in negatively regulating ERRα expression and breast cancer cell proliferation and migration. They suggest that manipulating the expression level of ERRα by microRNAs has the potential to influence breast cancer progression. PMID:22723937

  1. MiR-137 targets estrogen-related receptor alpha and impairs the proliferative and migratory capacity of breast cancer cells.

    PubMed

    Zhao, Yuanyin; Li, Yuping; Lou, Guiyu; Zhao, Li; Xu, Zhizhen; Zhang, Yan; He, Fengtian

    2012-01-01

    ERRα is an orphan nuclear receptor emerging as a novel biomarker of breast cancer. Over-expression of ERRα in breast tumor is considered as a prognostic factor of poor clinical outcome. The mechanisms underlying the dysexpression of this nuclear receptor, however, are poorly understood. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. In the present study, we have identified that the expression of ERRα is regulated by miR-137, a potential tumor suppressor microRNA. The bioinformatics search revealed two putative and highly conserved target-sites for miR-137 located within the ERRα 3'UTR at nt 480-486 and nt 596-602 respectively. Luciferase-reporter assay demonstrated that the two predicted target sites were authentically functional. They mediated the repression of reporter gene expression induced by miR-137 in an additive manner. Moreover, ectopic expression of miR-137 down-regulated ERRα expression at both protein level and mRNA level, and the miR-137 induced ERRα-knockdown contributed to the impaired proliferative and migratory capacity of breast cancer cells. Furthermore, transfection with miR-137 mimics suppressed at least two downstream target genes of ERRα-CCNE1 and WNT11, which are important effectors of ERRα implicated in tumor proliferation and migration. Taken together, our results establish a role of miR-137 in negatively regulating ERRα expression and breast cancer cell proliferation and migration. They suggest that manipulating the expression level of ERRα by microRNAs has the potential to influence breast cancer progression.

  2. Sexual Behavior Among Persons With Cognitive Impairments.

    PubMed

    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.

  3. Making Sense of Mild Cognitive Impairment: A Qualitative Exploration of the Patient's Experience

    ERIC Educational Resources Information Center

    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…

  4. Is social attention impaired in schizophrenia? Gaze, but not pointing gestures, is associated with spatial attention deficits.

    PubMed

    Dalmaso, Mario; Galfano, Giovanni; Tarqui, Luana; Forti, Bruno; Castelli, Luigi

    2013-09-01

    The nature of possible impairments in orienting attention to social signals in schizophrenia is controversial. The present research was aimed at addressing this issue further by comparing gaze and arrow cues. Unlike previous studies, we also included pointing gestures as social cues, with the goal of addressing whether any eventual impairment in the attentional response was specific to gaze signals or reflected a more general deficit in dealing with social stimuli. Patients with schizophrenia or schizoaffective disorder and matched controls performed a spatial-cuing paradigm in which task-irrelevant centrally displayed gaze, pointing finger, and arrow cues oriented rightward or leftward, preceded a lateralized target requiring a simple detection response. Healthy controls responded faster to spatially congruent targets than to spatially incongruent targets, irrespective of cue type. In contrast, schizophrenic patients responded faster to spatially congruent targets than to spatially incongruent targets only for arrow and pointing finger cues. No cuing effect emerged for gaze cues. The results support the notion that gaze cuing is impaired in schizophrenia, and suggest that this deficit may not extend to all social cues.

  5. Cognitive retraining for organizational impairment in obsessive-compulsive disorder.

    PubMed

    Buhlmann, Ulrike; Deckersbach, Thilo; Engelhard, Iris; Cook, Laura M; Rauch, Scott L; Kathmann, Norbert; Wilhelm, Sabine; Savage, Cary R

    2006-11-15

    Individuals with obsessive-compulsive disorder (OCD) have difficulties in organizing information during encoding associated with subsequent memory impairments. This study was designed to investigate whether impairments in organization in individuals with OCD can be alleviated with cognitive training. Thirty-five OCD subjects and 36 controls copied and recalled the Rey-Osterrieth Complex Figure Test (RCFT) [Osterrieth, P.A., 1944. Le test de copie d'une figure complexe: Contribution a l'étude de la perception et de la memoire (The test of copying a complex figure: A contribution to the study of perception and memory). Archive de Psychologie 30, 286-350.] before being randomly assigned to a training or non-training condition. The training condition was designed to improve the ability to organize complex visuospatial information in a meaningful way. The intervention phase was followed by another copy and recall trial of the RCFT. Both OCD and control subjects who underwent training improved more in organization and memory than subjects who did not receive organizational training, providing evidence that the training procedure was effective. OCD subjects improved more in organizational during encoding than control subjects, irrespective of whether or not they had received training. This suggests that organization impairment in OCD affects primarily the ability to spontaneously utilize strategies when faced with complex, ambiguous information but that the ability to implement such strategies when provided with additional trials is preserved. These findings support a distinction in OCD between failure to utilize a strategy and incapacity to implement a strategy.

  6. IMPAIRED VERBAL COMPREHENSION OF QUANTIFIERS IN CORTICOBASAL SYNDROME

    PubMed Central

    Troiani, Vanessa; Clark, Robin; Grossman, Murray

    2011-01-01

    Objective Patients with Corticobasal Syndrome (CBS) have atrophy in posterior parietal cortex. This region of atrophy has been previously linked with their quantifier comprehension difficulty, but previous studies used visual stimuli, making it difficult to account for potential visuospatial deficits in CBS patients. The current study evaluated comprehension of generalized quantifiers using strictly verbal materials. Method CBS patients, a brain-damaged control group (consisting of Alzheimer's Disease and frontotemporal dementia), and age-matched controls participated in this study. We assessed familiar temporal, spatial, and monetary domains of verbal knowledge comparatively. Judgment accuracy was only evaluated in statements for which patients demonstrated accurate factual knowledge about the target domain. Results We found that patients with CBS are significantly impaired in their ability to evaluate quantifiers compared to healthy seniors and a brain-damaged control group, even in this strictly visual task. This impairment was seen in the vast majority of individual CBS patients. Conclusions These findings offer additional evidence of quantifier impairment in CBS patients and emphasize that this impairment cannot be attributed to potential spatial processing impairments in patients with parietal disease. PMID:21381823

  7. Reporting by Physicians of Impaired Drivers and Potentially Impaired Drivers

    PubMed Central

    Berger, Jeffrey T; Rosner, Fred; Kark, Pieter; Bennett, Allen J

    2000-01-01

    Physicians routinely care for patients whose ability to operate a motor vehicle is compromised by a physical or cognitive condition. Physician management of this health information has ethical and legal implications. These concerns have been insufficiently addressed by professional organizations and public agencies. The legal status in the United States and Canada of reporting of impaired drivers is reviewed. The American Medical Association's position is detailed. Finally, the Bioethics Committee of the Medical Society of the State of New York proposes elements for an ethically defensible public response to this problem. PMID:11029682

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

    PubMed Central

    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

  9. Impaired strategic decision making in schizophrenia.

    PubMed

    Kim, Hyojin; Lee, Daeyeol; Shin, Young-Min; Chey, Jeanyung

    2007-11-14

    Adaptive decision making in dynamic social settings requires frequent re-evaluation of choice outcomes and revision of strategies. This requires an array of multiple cognitive abilities, such as working memory and response inhibition. Thus, the disruption of such abilities in schizophrenia can have significant implications for social dysfunctions in affected patients. In the present study, 20 schizophrenia patients and 20 control subjects completed two computerized binary decision-making tasks. In the first task, the participants played a competitive zero-sum game against a computer in which the predictable choice behavior was penalized and the optimal strategy was to choose the two targets stochastically. In the second task, the expected payoffs of the two targets were fixed and unaffected by the subject's choices, so the optimal strategy was to choose the target with the higher expected payoff exclusively. The schizophrenia patients earned significantly less money during the first task, even though their overall choice probabilities were not significantly different from the control subjects. This was mostly because patients were impaired in integrating the outcomes of their previous choices appropriately in order to maintain the optimal strategy. During the second task, the choices of patients and control subjects displayed more similar patterns. This study elucidated the specific components in strategic decision making that are impaired in schizophrenia. The deficit, which can be characterized as strategic stiffness, may have implications for the poor social adjustment in schizophrenia patients.

  10. Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.

    PubMed

    Mattes, F M; Vargas, A; Kopycinski, J; Hainsworth, E G; Sweny, P; Nebbia, G; Bazeos, A; Lowdell, M; Klenerman, P; Phillips, R E; Griffiths, P D; Emery, V C

    2008-05-01

    Human cytomegalovirus (HCMV) remains an important cause of morbidity after allotransplantation, causing a range of direct effects including hepatitis, pneumonitis, enteritis and retinitis. A dominant risk factor for HCMV disease is high level viral replication in blood but it remains unexplained why only a subset of patients develop such diseases. In this detailed study of 25 renal transplant recipients, we show that functional impairment of HCMV specific CD8 T cells in the production of interferon gamma was associated with a 14-fold increased risk of progression to high level replication. The CD8 T-cell impairment persisted during the period of high level replication and was more prominent in patients above 40 years of age (odds ratio = 1.37, p = 0.01) and was also evident in dialysis patients. Threshold levels of functional impairment were associated with an increased risk of future HCMV replication and there was a direct relationship between the functional capacity of HCMV ppUL83 CD8 T cells and HCMV load (R(2)= 0.83). These results help to explain why a subset of seropositive individuals develop HCMV replication and are at risk of end-organ disease and may facilitate the early identification of individuals who would benefit from targeted anti-HCMV therapy after renal transplantation.

  11. Attractive Toxic Sugar Bait (ATSB) For Control of Mosquitoes and Its Impact on Non-Target Organisms: A Review

    PubMed Central

    Fiorenzano, Jodi M.; Koehler, Philip G.; Xue, Rui-De

    2017-01-01

    Mosquito abatement programs contend with mosquito-borne diseases, insecticidal resistance, and environmental impacts to non-target organisms. However, chemical resources are limited to a few chemical classes with similar modes of action, which has led to insecticide resistance in mosquito populations. To develop a new tool for mosquito abatement programs that control mosquitoes while combating the issues of insecticidal resistance, and has low impacts of non-target organisms, novel methods of mosquito control, such as attractive toxic sugar baits (ATSBs), are being developed. Whereas insect baiting to dissuade a behavior, or induce mortality, is not a novel concept, as it was first introduced in writings from 77 AD, mosquito baiting through toxic sugar baits (TSBs) had been quickly developing over the last 60 years. This review addresses the current body of research of ATSB by providing an overview of active ingredients (toxins) include in TSBs, attractants combined in ATSB, lethal effects on mosquito adults and larvae, impact on non-target insects, and prospects for the use of ATSB. PMID:28394284

  12. Attractive Toxic Sugar Bait (ATSB) For Control of Mosquitoes and Its Impact on Non-Target Organisms: A Review.

    PubMed

    Fiorenzano, Jodi M; Koehler, Philip G; Xue, Rui-De

    2017-04-10

    Mosquito abatement programs contend with mosquito-borne diseases, insecticidal resistance, and environmental impacts to non-target organisms. However, chemical resources are limited to a few chemical classes with similar modes of action, which has led to insecticide resistance in mosquito populations. To develop a new tool for mosquito abatement programs that control mosquitoes while combating the issues of insecticidal resistance, and has low impacts of non-target organisms, novel methods of mosquito control, such as attractive toxic sugar baits (ATSBs), are being developed. Whereas insect baiting to dissuade a behavior, or induce mortality, is not a novel concept, as it was first introduced in writings from 77 AD, mosquito baiting through toxic sugar baits (TSBs) had been quickly developing over the last 60 years. This review addresses the current body of research of ATSB by providing an overview of active ingredients (toxins) include in TSBs, attractants combined in ATSB, lethal effects on mosquito adults and larvae, impact on non-target insects, and prospects for the use of ATSB.

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

    PubMed

    Becnel, J J; Johnson, M A

    1998-12-01

    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.

  14. Life Impairments in Adults with Medication-Treated ADHD

    ERIC Educational Resources Information Center

    Safren, Steven A.; Sprich, Susan E.; Cooper-Vince, Christine; Knouse, Laura E.; Lerner, Jonathan A.

    2010-01-01

    Objective: In developing psychosocial approaches to augment outcomes for medication-treated adults with ADHD, it is important to understand what types of life-impairments are most affected by continued ADHD symptoms that occur despite medication treatment. This may assist in delineating targets for interventions, as well as assessments of…

  15. The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.

    PubMed

    Lowes, Damon A; Thottakam, Bensita M V; Webster, Nigel R; Murphy, Michael P; Galley, Helen F

    2008-12-01

    Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondrial membrane potential was augmented (P<0.01) in most organs. These findings suggest that the use of mitochondria-targeted antioxidants such as MitoQ may be beneficial in sepsis.

  16. Self-motion impairs multiple-object tracking.

    PubMed

    Thomas, Laura E; Seiffert, Adriane E

    2010-10-01

    Investigations of multiple-object tracking aim to further our understanding of how people perform common activities such as driving in traffic. However, tracking tasks in the laboratory have overlooked a crucial component of much real-world object tracking: self-motion. We investigated the hypothesis that keeping track of one's own movement impairs the ability to keep track of other moving objects. Participants attempted to track multiple targets while either moving around the tracking area or remaining in a fixed location. Participants' tracking performance was impaired when they moved to a new location during tracking, even when they were passively moved and when they did not see a shift in viewpoint. Self-motion impaired multiple-object tracking in both an immersive virtual environment and a real-world analog, but did not interfere with a difficult non-spatial tracking task. These results suggest that people use a common mechanism to track changes both to the location of moving objects around them and to keep track of their own location. Copyright 2010 Elsevier B.V. All rights reserved.

  17. Grouping and trajectory storage in multiple object tracking: impairments due to common item motions.

    PubMed

    Suganuma, Mutsumi; Yokosawa, Kazuhiko

    2006-01-01

    In our natural viewing, we notice that objects change their locations across space and time. However, there has been relatively little consideration of the role of motion information in the construction and maintenance of object representations. We investigated this question in the context of the multiple object tracking (MOT) paradigm, wherein observers must keep track of target objects as they move randomly amid featurally identical distractors. In three experiments, we observed impairments in tracking ability when the motions of the target and distractor items shared particular properties. Specifically, we observed impairments when the target and distractor items were in a chasing relationship or moved in a uniform direction. Surprisingly, tracking ability was impaired by these manipulations even when observers failed to notice them. Our results suggest that differentiable trajectory information is an important factor in successful performance of MOT tasks. More generally, these results suggest that various types of common motion can serve as cues to form more global object representations even in the absence of other grouping cues.

  18. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts

    NASA Technical Reports Server (NTRS)

    Eckes, B.; Dogic, D.; Colucci-Guyon, E.; Wang, N.; Maniotis, A.; Ingber, D.; Merckling, A.; Langa, F.; Aumailley, M.; Delouvee, A.; hide

    1998-01-01

    Loss of a vimentin network due to gene disruption created viable mice that did not differ overtly from wild-type littermates. Here, primary fibroblasts derived from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured, and biological functions were studied in in vitro systems resembling stress situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild-type cells. Vimentin-deficient cells also displayed reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli. Reorganization of collagen fibrils and contraction of collagen lattices were severely impaired. The spatial organization of focal contact proteins, as well as actin microfilament organization was disturbed. Thus, absence of a vimentin filament network does not impair basic cellular functions needed for growth in culture, but cells are mechanically less stable, and we propose that therefore they are impaired in all functions depending upon mechanical stability.

  19. Membrane organization of virus and target cell plays a role in HIV entry.

    PubMed

    Dumas, Fabrice; Preira, Pascal; Salomé, Laurence

    2014-12-01

    The initial steps of the Human Immunodeficiency Virus (HIV) replication cycle play a crucial role that arbitrates viral tropism and infection efficiency. Before the release of its genome into the host cell cytoplasm, viruses operate a complex sequence of events that take place at the plasma membrane of the target cell. The first step is the binding of the HIV protein envelope (Env) to the cellular receptor CD4. This triggers conformational changes of the gp120 viral protein that allow its interaction with a co-receptor that can be either CCR5 or CXCR4, defining the tropism of the virus entering the cell. This sequential interaction finally drives the fusion of the viral and host cell membrane or to the endocytosis of the viruses. Here, we discuss how the membrane composition and organization of both the virus and the target cell can affect these steps and thus influence the capability of the viruses to infect cells. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. How Hearing Impairment Affects Sentence Comprehension: Using Eye Fixations to Investigate the Duration of Speech Processing

    PubMed Central

    Kollmeier, Birger; Brand, Thomas

    2015-01-01

    The main objective of this study was to investigate the extent to which hearing impairment influences the duration of sentence processing. An eye-tracking paradigm is introduced that provides an online measure of how hearing impairment prolongs processing of linguistically complex sentences; this measure uses eye fixations recorded while the participant listens to a sentence. Eye fixations toward a target picture (which matches the aurally presented sentence) were measured in the presence of a competitor picture. Based on the recorded eye fixations, the single target detection amplitude, which reflects the tendency of the participant to fixate the target picture, was used as a metric to estimate the duration of sentence processing. The single target detection amplitude was calculated for sentence structures with different levels of linguistic complexity and for different listening conditions: in quiet and in two different noise conditions. Participants with hearing impairment spent more time processing sentences, even at high levels of speech intelligibility. In addition, the relationship between the proposed online measure and listener-specific factors, such as hearing aid use and cognitive abilities, was investigated. Longer processing durations were measured for participants with hearing impairment who were not accustomed to using a hearing aid. Moreover, significant correlations were found between sentence processing duration and individual cognitive abilities (such as working memory capacity or susceptibility to interference). These findings are discussed with respect to audiological applications. PMID:25910503

  1. An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

    PubMed Central

    Bird, Luke; Tullis, Iain D. C.; Newman, Robert G.; Corroyer-Dulmont, Aurelien; Falzone, Nadia; Azad, Abul; Vallis, Katherine A.; Sansom, Owen J.; Muschel, Ruth J.; Vojnovic, Borivoj; Hill, Mark A.; Fokas, Emmanouil; Smart, Sean C.

    2017-01-01

    Introduction Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse. Methods A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours. Results The BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk. Conclusion This is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a

  2. Trace organic chemical pollutants from the lake waters of San Pablo City, Philippines by targeted and non-targeted analysis.

    PubMed

    Dimzon, Ian Ken D; Morata, Ann Selma; Müller, Janine; Yanela, Roy Kristian; Lebertz, Stephan; Weil, Heike; Perez, Teresita R; Müller, Jutta; Dayrit, Fabian M; Knepper, Thomas P

    2018-10-15

    More than half of the freshwater lakes in the Philippines are small with surface areas of <2 km 2 . The dynamics in these lakes are different from those in the bigger lakes. This study was conducted to determine the organic pollutants and their sources in three of the seven lakes of San Pablo City in Laguna, Philippines: lakes Palakpakin, Sampaloc, and Pandin. Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS) were used in the targeted and non-targeted analysis of the lake water samples. The three lakes are all volcanic crater lakes but are exposed to different anthropogenic activities, which includes domestic activities, livelihood (farming and aquaculture) and eco-tourism. Due to the presence of rice fields and fruit plantations, chlorpyrifos was detected in the three lakes while other pesticides like cypermethrin, picolinafen and quinoxyfen were additionally found in Lake Sampaloc, which is the biggest of the three lakes and located within the urbanized section of the city. Traces of different surfactants (linear alkylbenzene sulfonates, secondary alkyl sulfonates, alkyl sulfates, alkyl ether sulfates), biocide benzalkonium chloride, insect repellent diethyltoluamide, antibiotics (sulfadiazine and sulfamethoxazole), hypertension drug telmisartan, phosphate-based fire retardants, and artificial sweeteners (acesulfame, cyclamate, saccharin and sucralose) were detected in lakes Sampaloc and Palakpakin. The same surfactants, artificial sweeteners, insect repellant and phosphate-based fire retardants were also found in Lake Pandin, which is mainly used for eco-tourism activities like swimming and boating. The results of this study suggest that the organic pollutants present in the small lakes can be linked to the various human activities in the immediate lake environment. Because small lakes are more prone to environmental stresses, human activities in the said lakes must be regulated to ensure sustainable

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

    USGS Publications Warehouse

    Bradley, Paul M.; Journey, Celeste A.; Romanok, Kristin; Barber, Larry B.; Buxton, Herbert T.; Foreman, William T.; 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: < 0.001–0.012), providing a statistical inference tool for unmonitored contaminants. Due to multiple modes of action, high bioactivity, biorecalcitrance, and direct 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.

  4. Volunteering Is Associated with Lower Risk of Cognitive Impairment.

    PubMed

    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.

  5. A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Gang; Dong, Zhi-Yue; Cheng, Hong; Wan, Shuang-Shuang; Chen, Wei-Hai; Zou, Mei-Zhen; Huo, Jia-Wei; Deng, He-Xiang; Zhang, Xian-Zheng

    2015-09-01

    Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects.Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. Electronic supplementary information (ESI) available

  6. Exploring an alternative transportation program to reduce impaired driving.

    DOT National Transportation Integrated Search

    2001-11-01

    This study assessed the impact of an alternate ride home for persons who wanted to plan ahead for instances when they may be too impaired to drive, specifically targeting persons between the ages of 29 and 49. First, a series of focus groups was cond...

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

    PubMed

    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.

  8. Chemical structure determines target organ carcinogenesis in rats

    PubMed Central

    Carrasquer, C. A.; Malik, N.; States, G.; Qamar, S.; Cunningham, S.L.; Cunningham, A.R.

    2012-01-01

    SAR models were developed for 12 rat tumour sites using data derived from the Carcinogenic Potency Database. Essentially, the models fall into two categories: Target Site Carcinogen – Non-Carcinogen (TSC-NC) and Target Site Carcinogen – Non-Target Site Carcinogen (TSC-NTSC). The TSC-NC models were composed of active chemicals that were carcinogenic to a specific target site and inactive ones that were whole animal non-carcinogens. On the other hand, the TSC-NTSC models used an inactive category also composed of carcinogens but to any/all other sites but the target site. Leave one out validations produced an overall average concordance value for all 12 models of 0.77 for the TSC-NC models and 0.73 for the TSC-NTSC models. Overall, these findings suggest that while the TSC-NC models are able to distinguish between carcinogens and non-carcinogens, the TSC-NTSC models are identifying structural attributes that associate carcinogens to specific tumour sites. Since the TSC-NTSC models are composed of active and inactive compounds that are genotoxic and non-genotoxic carcinogens, the TSC-NTSC models may be capable of deciphering non-genotoxic mechanisms of carcinogenesis. Together, models of this type may also prove useful in anticancer drug development since they essentially contain chemicals moieties that target specific tumour site. PMID:23066888

  9. Negative Sentences in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Thornton, Rosalind; Rombough, Kelly; Martin, Jasmine; Orton, Linda

    2016-01-01

    This study used elicited production methodology to investigate the negative sentences that are produced by English-speaking children with specific language impairment (SLI). Negative sentences were elicited in contexts in which adults use the negative auxiliary verb doesn't (e.g., "It doesn't fit"). This form was targeted to see how…

  10. Multi-target determination of organic ultraviolet absorbents in organism tissues by ultrasonic assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Peng, Xianzhi; Jin, Jiabin; Wang, Chunwei; Ou, Weihui; Tang, Caiming

    2015-03-06

    A sensitive and reliable method was developed for multi-target determination of 13 most widely used organic ultraviolet (UV) absorbents (including UV filters and UV stabilizers) in aquatic organism tissues. The organic UV absorbents were extracted using ultrasonic-assisted extraction, purified via gel permeation chromatography coupled with silica gel column chromatography, and determined by ultra-high performance liquid chromatography-tandem mass spectrometry. Recoveries of the UV absorbents from organism tissues mostly ranged from 70% to 120% from fish filet with satisfactory reproducibility. Method quantification limits were 0.003-1.0ngg(-1) dry weight (dw) except for 2-ethylhexyl 4-methoxycinnamate. This method has been applied to analysis of the UV absorbents in wild and farmed aquatic organisms collected from the Pearl River Estuary, South China. 2-Hydroxy-4-methoxybenzophenone and UV-P were frequently detected in both wild and farmed marine organisms at low ngg(-1)dw. 3-(4-Methylbenzylidene)camphor and most of the benzotriazole UV stabilizers were also frequently detected in maricultured fish. Octocrylene and 2-ethylhexyl 4-methoxycinnamate were not detected in any sample. This work lays basis for in-depth study about bioaccumulation and biomagnification of the UV absorbents in marine environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Carotid and aortic stiffness in essential hypertension and their relation with target organ damage: the CATOD study

    PubMed Central

    Bruno, Rosa Maria; Cartoni, Giulia; Stea, Francesco; Armenia, Sabina; Bianchini, Elisabetta; Buralli, Simona; Giannarelli, Chiara; Taddei, Stefano; Ghiadoni, Lorenzo

    2017-01-01

    Objective The objective of the study is to investigate in the hypertensive population the possible differential association between increased aortic and/or carotid stiffness and organ damage in multiple districts, such as the kidney, the vessels, and the heart. Methods In 314 essential hypertensive patients, carotid–femoral pulse wave velocity (cfPWV, by applanation tonometry) and carotid stiffness (from ultrasound images analysis), together with left ventricular hypertrophy, carotid intima–media thickness, urinary albumin–creatinin ratio, and glomerular filtration rate were measured. Increased cfPWV and carotid stiffness were defined according to either international reference values or the 90th percentile of a local control group (110 age and sex-matched healthy individuals). Results When considering the 90th percentile of a local control group, increased cfPWV was associated with reduced glomerular filtration rate, either when carotid stiffness was increased [odds ratio (OR) 13.27 (confidence limits (CL) 95% 3.86–45.58)] or not [OR 7.39 (CL95% 2.25–24.28)], whereas increased carotid stiffness was associated with left ventricular hypertrophy, either when cfPWV was increased [OR 2.86 (CL95% 1.15–7.09)] or not [OR 2.81 (CL95% 1.13–6.97)]. No association between increased cfPWV or carotid stiffness and target organ damage was found when cutoffs obtained by international reference values were used. The concomitance of both increased cfPWV and carotid stiffness did not have an additive effect on organ damage. Conclusion Aortic and carotid stiffness are differentially associated with target organ damage in hypertensive patients. Regional arterial stiffness as assessed by cfPWV is associated with renal organ damage and local carotid stiffness with cardiac organ damage. PMID:27841779

  12. Gut as a target for cadmium toxicity.

    PubMed

    Tinkov, Alexey A; Gritsenko, Viktor A; Skalnaya, Margarita G; Cherkasov, Sergey V; Aaseth, Jan; Skalny, Anatoly V

    2018-04-01

    The primary objective of the present study was to review the impact of Cd exposure on gut microbiota and intestinal physiology, as well as to estimate whether gut may be considered as the target for Cd toxicity. The review is based on literature search in available databases. The existing data demonstrate that the impact of Cd on gut physiology is two-sided. First, Cd exposure induces a significant alteration of bacterial populations and their relative abundance in gut (increased Bacteroidetes-to-Firmicutes ratio), accompanied by increased lipopolysaccharide (LPS) production, reflecting changed metabolic activity of the intestinal microbiome. Second, in intestinal wall Cd exposure induces inflammatory response and cell damage including disruption of tight junctions, ultimately leading to increased gut permeability. Together with increased LPS production, impaired barrier function causes endotoxinemia and systemic inflammation. Hypothetically, Cd-induced increase gut permeability may also result in increased bacterial translocation. On the one hand, bacteriolysis may be associated with aggravation of endotoxemia. At the same time, together with Cd-induced impairment of macrophage inflammatory response, increased bacterial translocation may result in increased susceptibility to infections. Such a supposition is generally in agreement with the finding of higher susceptibility of Cd-exposed mice to infections. The changed microbiome metabolic activity and LPS-induced systemic inflammation may have a significant impact on target organs. The efficiency of probiotics in at least partial prevention of the local (intestinal) and systemic toxic effects of cadmium confirms the role of altered gut physiology in Cd toxicity. Therefore, probiotic treatment may be considered as the one of the strategies for prevention of Cd toxicity in parallel with chelation, antioxidant, and anti-inflammatory therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. West Virginia’s impaired driving high-visibility enforcement campaign, 2003-2005

    DOT National Transportation Integrated Search

    2007-08-01

    In 2002, West Virginia became a Strategic Evaluation State for the National Highway Traffic Safety Administration's Impaired Driving High-Visibility Enforcement campaign. The State implemented NHTSA's model publicity and enforcement program in target...

  14. Early life influences on cognitive impairment among oldest old Chinese.

    PubMed

    Zhang, Zhenmei; Gu, Danan; Hayward, Mark D

    2008-01-01

    This article examines the effects of early life socioeconomic conditions on the risk of cognitive impairment among oldest old persons in China. We also examine whether adult socioeconomic status mediates the association between early life socioeconomic status and cognitive impairment in old age. Data derived from two waves (1998-2000) of the Chinese Longitudinal Healthy Longevity Survey. We estimated logistic and multinomial regression models of cognitive impairment for a nationwide sample of people aged 80 to 105 (N = 8,444). Among both men and women, urban residence in early life as well as education was associated with lower odds of cognitive impairment at baseline. We found modest support for a protective effect of advantaged childhood background on the odds of cognitive impairment onset during the 2-year follow-up, especially among women. Our findings suggest that socioeconomic environment throughout the life course, early life in particular, can influence the risk of cognitive impairment in old age. Not only can public policy that targets illiteracy, hunger, and poverty improve the lives of tens of thousands of children, but ultimately such investments will pay significant dividends many decades later in enhancing the cognitive well-being of older persons.

  15. Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis

    PubMed Central

    Cao, Zhongwei; Ye, Tinghong; Sun, Yue; Ji, Gaili; Shido, Koji; Chen, Yutian; Luo, Lin; Na, Feifei; Li, Xiaoyan; Huang, Zhen; Ko, Jane L.; Mittal, Vivek; Qiao, Lina; Chen, Chong; Martinez, Fernando J.; Rafii, Shahin; Ding, Bi-Sen

    2017-01-01

    The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. Here, we show that targeting both the vascular niche and perivascular fibroblasts establishes “hospitable soil” to foster incorporation of “seed”, in this case the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NADPH Oxidase 4 (NOX4) synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs (HgfiΔEC/iΔEC) aberrantly upregulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially-inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in HgfiΔEC/iΔEC mice recapitulated the phenotype of human and mouse fibrotic livers and lungs. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration. PMID:28855398

  16. Impaired Decisional Impulsivity in Pathological Videogamers

    PubMed Central

    Irvine, Michael A.; Worbe, Yulia; Bolton, Sorcha; Harrison, Neil A.; Bullmore, Edward T.; Voon, Valerie

    2013-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:24146789

  17. Parkinson's Disease, Diabetes and Cognitive Impairment.

    PubMed

    Ashraghi, Mohammad R; Pagano, Gennaro; Polychronis, Sotirios; Niccolini, Flavia; Politis, Marios

    2016-01-01

    Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. A narrative review using MEDLINE database. Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

  18. Vision Impairment and Ocular Morbidity in a Refugee Population in Malawi.

    PubMed

    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 <6/18) was present in 5.4% (95% CI, 3.6 to 7.1) of the participants. The principal causes of blindness, severe 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

  19. Targeting Insulin Signaling for the Treatment of Alzheimer's Disease.

    PubMed

    Chen, Yanxing; Zhang, Jianfang; Zhang, Baorong; Gong, Cheng-Xin

    2016-01-01

    Sporadic Alzheimer's disease (AD) is caused by multiple etiological factors, among which impaired brain insulin signaling and decreased brain glucose metabolism are important metabolic factors. Contrary to previous belief that insulin would not act in the brain, studies in the last three decades have proven important roles of insulin and insulin signaling in various biological functions in the brain. Impaired brain insulin signaling or brain insulin resistance and its role in the molecular pathogenesis of sporadic AD have been demonstrated. Thus, targeting brain insulin signaling for the treatment of cognitive impairment and AD has now attracted much attention in the field of AD drug discovery. This article reviews recent studies that target brain insulin signaling, especially those investigations on intranasal insulin administration and drugs that improve insulin sensitivity, including incretins, dipeptidyl peptidase IV inhibitors, thiazolidinediones, and metformin. These drugs have been previously approved for the treatment of diabetes mellitus, which could expedite their development for the treatment of AD. Although larger clinical trials are needed for validating their efficacy for the treatment of cognitive impairment and AD, results of animal studies and clinical trials available to date are encouraging.

  20. Perceptual salience does not influence emotional arousal's impairing effects on top-down attention.

    PubMed

    Sutherland, Matthew R; McQuiggan, Douglas A; Ryan, Jennifer D; Mather, Mara

    2017-06-01

    Emotional arousal impairs top-down attentional control while strengthening bottom-up attentional biases. In this study, we examined whether top-down impairments due to arousal can be modulated by increasing the perceptual salience of the target stimulus. To examine this question, we briefly displayed positive and negative arousing images prior to the encoding of 2 emotionally neutral items, 1 of which was to be remembered and 1 of which was perceptually salient (the to-be-remembered and the salient items were either the same item or different items). Eye tracking was used to measure attention biases during the encoding of the 2 competing neutral items, as well as to measure pupillary responses to the preceding modulator image. Viewing emotional images, regardless of valence, impaired top-down attention to animate stimulus targets (i.e., animals), regardless of perceptual salience. However, these effects on encoding had no influence on recognition memory. Taken together, these findings reveal that exposure to emotionally arousing images impairs top-down attention to animate stimuli, regardless of whether that stimulus is perceptually salient. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Relationship between increased arterial stiffness and other markers of target organ damage.

    PubMed

    Rodilla, Enrique; Costa, José Antonio; Pérez-Lahiguera, Francisco; González, Carmen; Pascual, José María

    2010-04-24

    The purpose of the present study was to assess the relationship of arterial stiffness with other markers of target organ damage, and the clinical factors related to it. Cross-sectional study that included 208 (115 men) never treated hypertensive, non-diabetic patients (mean age, 49+/-12 years). In addition to a full clinical study, 24h ambulatory blood pressure (BP), and determination of left ventricular hypertrophy (LVH) and microalbuminuria were performed. Clinical arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) obtained with applanation tonometry (SphygmoCor-System). PWV was 8.3 (7.3-9.9)m/s (median, interquartile range). Stepwise regression analysis revealed that age (beta=0.086, p<0.001), 24-h pulse pressure (beta=0.058, p<0.001), and low-density lipoprotein (LDL) cholesterol (beta=0.009, p<0.013) were independent determinants of PWV. PWV>12m/s (indicating target organ lesion) was present in only 16 (7.7%) patients, less frequent than LVH (28% of the patients) and microalbuminuria (16%). However, of the 16 patients with elevated PWV, 10 (62%) had neither LVH or microalbuminuria. In a logistic multivariate regression analysis the factors related to elevated PWV were age > or =45 in man and > or =55 in women (OR: 23.8, 95% CI: 2.7-195.5; p=0.004), LDL cholesterol > or =160mg/dl (OR: 10.6, 95% CI: 2.6-42.7; p=0.001) and increased 24-h pulse pressure > or =55mmHg (OR: 3.9, 95% CI: 1.2-12.9; p=0.03). In untreated middle age hypertensives arterial stiffness assessed by PWV is less frequent than LVH or microalbuminuria. PWV is mainly related to age, LDL cholesterol, and pulse pressure values. 2009 Elsevier España, S.L. All rights reserved.

  2. Impaired semantic inhibition during lexical ambiguity repetition in Parkinson's disease.

    PubMed

    Copland, David A; Sefe, Gameli; Ashley, Jane; Hudson, Carrie; Chenery, Helen J

    2009-09-01

    Impairments of semantic processing and inhibition have been observed in Parkinson's disease (PD), however, the consequences of faulty meaning selection and suppression have not been considered in terms of subsequent lexical processing. The present study employed a lexical ambiguity repetition paradigm where the first presentation of an ambiguity paired with a target biasing its dominant or subordinate meaning (e.g., bank - money or bank - river) was followed after several intervening trials by a presentation of the same ambiguity paired with a different target that biases the same (congruent) or a different (incongruent) meaning to that biased on the first presentation. Meaning dominance (dominant or subordinate weaker meanings) and interstimulus interval (ISI) were manipulated. Analyses conducted on the second presentation indicated priming of congruent meanings and no priming for the incongruent meanings at both short and long ISIs in the healthy controls, consistent with suppression of meanings competing with the representation biased in the first presentation. In contrast, the PD group failed to dampen activation for the incongruent meaning at the long ISI when the first presentation was subordinate. This pattern is consistent with an impairment of meaning suppression which is observed under controlled processing conditions and varies as a function of meaning dominance of the first presentation. These findings further refine our understanding of lexical-semantic impairments in PD and suggest a mechanism that may contribute to discourse comprehension impairments in this population.

  3. [Musculoskeletal system as a target organ of a frailty processes].

    PubMed

    Zlobina, I A; Krivtsunov, A N; Bogat, S V; Prashchayeu, K I

    Pathology of the musculoskeletal system is widespread in the population and is one of the most common diseases of patients in older age groups. The most significant of them are osteoporosis, osteoarthritis and sarcopenia. All three components separately, of course, lead to lower quality of life. In our work we show the mechanisms of interference of these states at each other, and their combined impact on the musculoskeletal system as a target organ processes senile asthenia. Osteoarthritis, osteoporosis, and sarcopenia, and especially their combination lead to hypomobility. Hypomobility under the influence of external factors is one of the leading syndromes potentiating aggravation processes senile asthenia. Thus, the mechanism of re-entry is triggered, and a vicious circle leading to fatal medical-social and social consequences. It is shown that changes in the musculoskeletal system should be considered as a single aging within senile asthenia, and all used and newly created medical and social rehabilitation and prevention programs should be integrated in nature.

  4. Chemoprevention of obesity by dietary natural compounds targeting mitochondrial regulation.

    PubMed

    Lai, Ching-Shu; Wu, Jia-Ching; Ho, Chi-Tang; Pan, Min-Hsiung

    2017-06-01

    Mitochondria are at the center stage in the control of energy homeostasis in many organs and tissues including adipose tissue. Recently, abundant evidence from experimental studies has clearly supported the strong correlation between mitochondrial dysfunction in adipocytes and obesity. Various physiological conditions such as excessive nutrition, genetic factors, hypoxia, and toxins disrupt mitochondrial function by impairing mitochondrial biogenesis, dynamics, and oxidative capacity. Mitochondrial dysfunction in adipocytes could have an impact on differentiation, adipogenesis, insulin sensitivity, and the significant alteration in their metabolic function, which ultimately results in obesity and type 2 diabetes. Numerous dietary natural compounds are the subject of research for the prevention and treatment of obesity through reprogramming multiple metabolic pathways. Some of them have the potential against obesity by modulating insulin signaling, decreasing oxidative damage, downregulating adipokines secretion, and increasing mitochondrial DNA that improves mitochondrial function and thus maintain metabolic homeostasis. Here, we focus on and summarize and briefly discuss the currently known targets and the mitochondria-targeting effects of dietary natural compounds in the intervention of obesity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Relationships between divided attention and working memory impairment in people with schizophrenia.

    PubMed

    Gray, Bradley E; Hahn, Britta; Robinson, Benjamin; Harvey, Alex; Leonard, Carly J; Luck, Steven J; Gold, James M

    2014-11-01

    Recent studies suggest that people with schizophrenia (PSZ) have difficulty distributing their attention broadly. Other research suggests that PSZ have reduced working memory (WM) capacity. This study tested whether these findings reflect a common underlying deficit. We measured the ability to distribute attention by means of the Useful Field of View (UFOV) task, in which participants must distribute attention so that they can discriminate a foveal target and simultaneously localize a peripheral target. Participants included 50 PSZ and 52 healthy control subjects. We found that PSZ exhibited severe impairments in UFOV performance, that UFOV performance was highly correlated with WM capacity in PSZ (r = -.61), and that UFOV impairments could not be explained by either impaired low-level processing or a generalized deficit. These results suggest that a common mechanism explains deficits in the ability to distribute attention broadly, reduced WM capacity, and other aspects of impaired cognition in schizophrenia. We hypothesize that this mechanism may involve abnormal local circuit dynamics that cause a hyperfocusing of resources onto a small number of internal representations. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

    PubMed

    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.

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

    PubMed Central

    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

  8. Improved prediction of peptide detectability for targeted proteomics using a rank-based algorithm and organism-specific data.

    PubMed

    Qeli, Ermir; Omasits, Ulrich; Goetze, Sandra; Stekhoven, Daniel J; Frey, Juerg E; Basler, Konrad; Wollscheid, Bernd; Brunner, Erich; Ahrens, Christian H

    2014-08-28

    The in silico prediction of the best-observable "proteotypic" peptides in mass spectrometry-based workflows is a challenging problem. Being able to accurately predict such peptides would enable the informed selection of proteotypic peptides for targeted quantification of previously observed and non-observed proteins for any organism, with a significant impact for clinical proteomics and systems biology studies. Current prediction algorithms rely on physicochemical parameters in combination with positive and negative training sets to identify those peptide properties that most profoundly affect their general detectability. Here we present PeptideRank, an approach that uses learning to rank algorithm for peptide detectability prediction from shotgun proteomics data, and that eliminates the need to select a negative dataset for the training step. A large number of different peptide properties are used to train ranking models in order to predict a ranking of the best-observable peptides within a protein. Empirical evaluation with rank accuracy metrics showed that PeptideRank complements existing prediction algorithms. Our results indicate that the best performance is achieved when it is trained on organism-specific shotgun proteomics data, and that PeptideRank is most accurate for short to medium-sized and abundant proteins, without any loss in prediction accuracy for the important class of membrane proteins. Targeted proteomics approaches have been gaining a lot of momentum and hold immense potential for systems biology studies and clinical proteomics. However, since only very few complete proteomes have been reported to date, for a considerable fraction of a proteome there is no experimental proteomics evidence that would allow to guide the selection of the best-suited proteotypic peptides (PTPs), i.e. peptides that are specific to a given proteoform and that are repeatedly observed in a mass spectrometer. We describe a novel, rank-based approach for the prediction

  9. Age-Related Sensory Impairments and Risk of Cognitive Impairment

    PubMed Central

    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 < 24 or history of dementia or Alzheimer’s disease. Hearing 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 < 1.55 log units in the better eye and olfactory impairment was a San Diego Odor Identification Test score of < 6. Results Hearing, visual, and olfactory 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

  10. Age-Related Sensory Impairments and Risk of Cognitive Impairment.

    PubMed

    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 <24 or history 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 <1.55 log units in the better eye, and olfactory impairment was a San Diego Odor Identification Test score of <6. Hearing, visual, and olfactory 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.

  11. Risk assessment of Bt crops on the non-target plant-associated insects and soil organisms.

    PubMed

    Yaqoob, Amina; Shahid, Ahmad Ali; Samiullah, Tahir Rehman; Rao, Abdul Qayyum; Khan, Muhammad Azmat Ullah; Tahir, Sana; Mirza, Safdar Ali; Husnain, Tayyab

    2016-06-01

    Transgenic plants containing Bacillus thuringiensis (Bt) genes are being cultivated worldwide to express toxic insecticidal proteins. However, the commercial utilisation of Bt crops greatly highlights biosafety issues worldwide. Therefore, assessing the risks caused by genetically modified crops prior to their commercial cultivation is a critical issue to be addressed. In agricultural biotechnology, the goal of safety assessment is not just to identify the safety of a genetically modified (GM) plant, rather to demonstrate its impact on the ecosystem. Various experimental studies have been made worldwide during the last 20 years to investigate the risks and fears associated with non-target organisms (NTOs). The NTOs include beneficial insects, natural pest controllers, rhizobacteria, growth promoting microbes, pollinators, soil dwellers, aquatic and terrestrial vertebrates, mammals and humans. To highlight all the possible risks associated with different GM events, information has been gathered from a total of 76 articles, regarding non-target plant and soil inhabiting organisms, and summarised in the form of the current review article. No significant harmful impact has been reported in any case study related to approved GM events, although critical risk assessments are still needed before commercialisation of these crops. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  12. Disagreement between Parent and Adolescent Reports of Functional Impairment

    ERIC Educational Resources Information Center

    Kramer, Teresa L.; Phillips, Susan D.; Hargis, Michael B.; Miller, Terri L.; Burns, Barbara J.; Robbins, James M.

    2004-01-01

    Objective: Adolescents' functional impairment has become increasingly important as a criterion for diagnosis and service eligibility as well as a target of therapeutic intervention in mental health settings. This study examines three critical issues in measuring functioning: 1) agreement between parent and adolescent reports of functioning, 2)…

  13. Non-target organism effects tests on Vip3A and their application to the ecological risk assessment for cultivation of MIR162 maize.

    PubMed

    Raybould, Alan; Vlachos, Demetra

    2011-06-01

    Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) provide economic, environmental and health benefits by maintaining or increasing crop yields with fewer applications of insecticide. To sustain these benefits, it is important to delay the evolution of insect resistance to the proteins, and to ensure that the proteins do not harm non-target organisms, particularly those that may control secondary pests that would otherwise flourish because of reduced insecticide applications. Vip3A is a Bt vegetative insecticidal protein that is active against lepidopterous pests. It has a different mode of action from other proteins for control of Lepidoptera in current Bt crops, and when combined with these proteins, it should help to delay the evolution of pest resistance to Bt crops. This paper presents data on the effects of Vip3A on non-target organisms, and an ecological risk assessment of MIR162 maize, which expresses Vip3Aa20. Laboratory studies indicate few adverse effects of Vip3A to non-target organisms: 11 of 12 species tested showed no adverse effects when exposed to high concentrations of Vip3A relative to estimated exposures resulting from cultivation of MIR162 maize. Daphnia magna exposed to Vip3Aa20 were unaffected in terms of survival or fecundity, but grew slightly more slowly than unexposed controls. The data indicate that cultivation of MIR162 maize poses negligible risk to non-target organisms, and that crops producing Vip3A are unlikely to adversely affect biological control organisms such that benefits from reduced insecticide applications are lost.

  14. How hearing impairment affects sentence comprehension: using eye fixations to investigate the duration of speech processing.

    PubMed

    Wendt, Dorothea; Kollmeier, Birger; Brand, Thomas

    2015-04-24

    The main objective of this study was to investigate the extent to which hearing impairment influences the duration of sentence processing. An eye-tracking paradigm is introduced that provides an online measure of how hearing impairment prolongs processing of linguistically complex sentences; this measure uses eye fixations recorded while the participant listens to a sentence. Eye fixations toward a target picture (which matches the aurally presented sentence) were measured in the presence of a competitor picture. Based on the recorded eye fixations, the single target detection amplitude, which reflects the tendency of the participant to fixate the target picture, was used as a metric to estimate the duration of sentence processing. The single target detection amplitude was calculated for sentence structures with different levels of linguistic complexity and for different listening conditions: in quiet and in two different noise conditions. Participants with hearing impairment spent more time processing sentences, even at high levels of speech intelligibility. In addition, the relationship between the proposed online measure and listener-specific factors, such as hearing aid use and cognitive abilities, was investigated. Longer processing durations were measured for participants with hearing impairment who were not accustomed to using a hearing aid. Moreover, significant correlations were found between sentence processing duration and individual cognitive abilities (such as working memory capacity or susceptibility to interference). These findings are discussed with respect to audiological applications. © The Author(s) 2015.

  15. The vascular endothelium in diabetes--a therapeutic target?

    PubMed

    Mather, Kieren J

    2013-03-01

    Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.

  16. Visual impairment in Finnish Usher syndrome type III.

    PubMed

    Plantinga, Rutger F; Pennings, Ronald J E; Huygen, Patrick L M; Sankila, Eeva-Marja; Tuppurainen, Kaija; Kleemola, Leenamaija; Cremers, Cor W R J; Deutman, August F

    2006-02-01

    To evaluate visual impairment in Finnish Usher syndrome type 3 (USH3) and compare this with visual impairment in Usher syndrome types 1b (USH1b) and 2a (USH2a). We carried out a retrospective study of 28 Finnish USH3 patients, 24 Dutch USH2a patients and 17 Dutch USH1b patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS*) and functional vision score (FVS*) related to age were performed for all patients. The FFS* and FVS* were calculated using the isoptre V-4 test target instead of the usual III-4 target. Statistical tests relating to regression lines and Student's t-test were used to compare between USH3 patients and the other genetic subtypes of Usher syndrome. Cross-sectional analyses revealed significant deterioration in the FAS (1.3% per year), FFS* (1.4% per year) and FVS* (1.8% per year) with advancing age in the USH3 patient group. At a given age the USH3 patients showed significantly poorer visual field function than the USH2a patients. The rate of deterioration in visual function in Finnish USH3 patients was fairly similar to that in Dutch USH1b or USH2a patients. At a given age, visual field impairment in USH3 patients was similar to that in USH1b patients but poorer than in USH2a patients.

  17. Effects of social cognitive impairment on speech disorder in schizophrenia.

    PubMed

    Docherty, Nancy M; McCleery, Amanda; Divilbiss, Marielle; Schumann, Emily B; Moe, Aubrey; Shakeel, Mohammed K

    2013-05-01

    Disordered speech in schizophrenia impairs social functioning because it impedes communication with others. Treatment approaches targeting this symptom have been limited by an incomplete understanding of its causes. This study examined the process underpinnings of speech disorder, assessed in terms of communication failure. Contributions of impairments in 2 social cognitive abilities, emotion perception and theory of mind (ToM), to speech disorder were assessed in 63 patients with schizophrenia or schizoaffective disorder and 21 nonpsychiatric participants, after controlling for the effects of verbal intelligence and impairments in basic language-related neurocognitive abilities. After removal of the effects of the neurocognitive variables, impairments in emotion perception and ToM each explained additional variance in speech disorder in the patients but not the controls. The neurocognitive and social cognitive variables, taken together, explained 51% of the variance in speech disorder in the patients. Schizophrenic disordered speech may be less a concomitant of "positive" psychotic process than of illness-related limitations in neurocognitive and social cognitive functioning.

  18. Assistive obstacle detection and navigation devices for vision-impaired users.

    PubMed

    Ong, S K; Zhang, J; Nee, A Y C

    2013-09-01

    Quality of life for the visually impaired is an urgent worldwide issue that needs to be addressed. Obstacle detection is one of the most important navigation tasks for the visually impaired. In this research, a novel range sensor placement scheme is proposed in this paper for the development of obstacle detection devices. Based on this scheme, two prototypes have been developed targeting at different user groups. This paper discusses the design issues, functional modules and the evaluation tests carried out for both prototypes. Implications for Rehabilitation Visual impairment problem is becoming more severe due to the worldwide ageing population. Individuals with visual impairment require assistance from assistive devices in daily navigation tasks. Traditional assistive devices that assist navigation may have certain drawbacks, such as the limited sensing range of a white cane. Obstacle detection devices applying the range sensor technology can identify road conditions with a higher sensing range to notify the users of potential dangers in advance.

  19. Acute Alcohol Consumption Impairs Controlled but Not Automatic Processes in a Psychophysical Pointing Paradigm

    PubMed Central

    Johnston, Kevin; Timney, Brian; Goodale, Melvyn A.

    2013-01-01

    Numerous studies have investigated the effects of alcohol consumption on controlled and automatic cognitive processes. Such studies have shown that alcohol impairs performance on tasks requiring conscious, intentional control, while leaving automatic performance relatively intact. Here, we sought to extend these findings to aspects of visuomotor control by investigating the effects of alcohol in a visuomotor pointing paradigm that allowed us to separate the influence of controlled and automatic processes. Six male participants were assigned to an experimental “correction” condition in which they were instructed to point at a visual target as quickly and accurately as possible. On a small percentage of trials, the target “jumped” to a new location. On these trials, the participants’ task was to amend their movement such that they pointed to the new target location. A second group of 6 participants were assigned to a “countermanding” condition, in which they were instructed to terminate their movements upon detection of target “jumps”. In both the correction and countermanding conditions, participants served as their own controls, taking part in alcohol and no-alcohol conditions on separate days. Alcohol had no effect on participants’ ability to correct movements “in flight”, but impaired the ability to withhold such automatic corrections. Our data support the notion that alcohol selectively impairs controlled processes in the visuomotor domain. PMID:23861934

  20. Parenting Mediates Symptoms and Impairment in Children with ADHD-Inattentive Type

    PubMed Central

    Haack, Lauren; Villodas, Miguel T.; McBurnett, Keith; Hinshaw, Stephen; Pfiffner, Linda

    2015-01-01

    The current study investigates potential pathways between inattentive symptom severity, positive and negative parenting practices, and functional impairment (i.e., academic, social, and home impairment) in a sample of children diagnosed with ADHD, Predominantly Inattentive Type (ADHD-I). Participants included 199 children and their parents and teachers enrolled in a randomized clinical trial investigating the efficacy of an integrated psychosocial intervention for children with ADHD-I. Boys constituted just over half the sample; children averaged 8.6 years of age (range 7–11) and were from varied ethnic/racial backgrounds. As part of the initial screening and assessment procedures, parents and teachers completed questionnaires assessing child behavior and parent/family functioning. Results supported both main effects of symptoms and parenting on impairment, as well as a mediational path between symptoms and impairment via parenting, as observed by parents in the home setting. Specifically, higher severity of inattention was associated with higher rates of homework, social, and home impairment. Negative parenting contributed to homework and home impairment, and positive and negative parenting contributed to social impairment, incrementally above and beyond the impact of inattention symptom severity alone. Negative parenting partially mediated the relationship between inattentive symptom severity and impairment, such that higher rates of inattention were associated with higher rates of negative parenting, which in turn was associated with higher rates of homework, social, and home impairment. Results provide support for underlying mechanisms for associations between symptoms and impairment in children with ADHD-I, and also identify potential intervention targets to improve impairment experienced by these children. PMID:25411896

  1. Visual acuity and visual field impairment in Usher syndrome.

    PubMed

    Edwards, A; Fishman, G A; Anderson, R J; Grover, S; Derlacki, D J

    1998-02-01

    To determine the extent of visual acuity and visual field impairment in patients with types 1 and 2 Usher syndrome. The records of 53 patients with type 1 and 120 patients with type 2 Usher syndrome were reviewed for visual acuity and visual field area at their most recent visit. Visual field areas were determined by planimetry of the II4e and V4e isopters obtained with a Goldmann perimeter. Both ordinary and logistic regression models were used to evaluate differences in visual acuity and visual field impairment between patients with type 1 and type 2 Usher syndrome. The difference in visual acuity of the better eye between patients with type 1 and type 2 varied by patient age (P=.01, based on a multiple regression model). The maximum difference in visual acuity between the 2 groups occurred during the third and fourth decades of life (with the type 1 patients being more impaired), while more similar acuities were seen in both younger and older patients. Fifty-one percent (n=27) of the type 1 patients had a visual acuity of 20/40 or better in at least 1 eye compared with 72% (n=87) of the type 2 patients (age-adjusted odds ratio, 3.9). Visual field area to both the II4e (P=.001) and V4e (P<.001) targets was more impaired in the better eye of type 1 patients than type 2 patients. A concentric central visual field greater than 20 degrees in at least 1 eye was present in 20 (59%) of the available 34 visual fields of type 1 patients compared with 70 (67%) of the available 104 visual fields of type 2 patients (age-adjusted odds ratio, 2.9) with the V4e target and in 6 (21%) of the available 29 visual fields of type 1 patients compared with 36 (38%) of the available 94 visual fields of type 2 patients (age-adjusted odds ratio, 4.9) with the II4e target. The fraction of patients who had a visual acuity of 20/40 or better and a concentric central visual field greater than 20 degrees to the II4e target in at least 1 eye was 17% (n=5) in the type 1 patients and 35% (n=33

  2. Effect of malachite green toxicity on non target soil organisms.

    PubMed

    Gopinathan, R; Kanhere, J; Banerjee, J

    2015-02-01

    Although malachite green (MG), is banned in Europe and US for its carcinogenic and teratogenic effect, the dye being cheap, is persistently used in various countries for fish farming, silk, dye, leather and textile industries. Current research, however, fails to elucidate adequate knowledge concerning the effects of MG in our ecosystem. In the present investigation, for the first time, an attempt has been made to study the effects of MG on soil biota by testing Bacillus subtilis, Azotobacter chroococcum, Saccharomyces cerevisiae, Penicillium roqueforti, Eisenia fetida and seeds of three crop plants of different families. Various tests were conducted for determining cytotoxicity, genotoxicity, acute toxicity, morphological and germination effect. Our data confirmed MG toxicity on fungi and bacteria (gram positive and gram negative organisms) showing elevated level of ROS. Genotoxicity caused in the microorganisms was detected by DNA polymorphism and fragmentation. Also, scanning electron microscopy data suggests that the inhibitory effect of MG to these beneficial microbes in the ecosystem might be due to pore formation in the cell and its eventual disruption. Filter paper and artificial soil test conducted on earthworms demonstrated a LC 50 of 2.6 mg cm(-2) and 1.45 mg kg(-1) respectively with severe morphological damage. However, seed germination of Mung bean, Wheat and Mustard was found to be unaffected in presence of MG up to 100 mL(-1) concentration. Thus, understanding MG toxicity in non target soil organisms and emphasis on its toxicological effects would potentially explicate its role as an environmental contaminant. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Attentional Blink Impairment in Social Anxiety Disorder: Depression Comorbidity Matters

    PubMed Central

    Morrison, Amanda S.; Brozovich, Faith A.; Lakhan-Pal, Shreya; Jazaieri, Hooria; Goldin, Philippe R.; Heimberg, Richard G.; Gross, James J.

    2015-01-01

    Background and Objectives Difficulties with attentional control have long been thought to play a key role in anxiety and depressive disorders. However, the nature and extent of attentional control difficulties in social anxiety disorder (SAD) are not yet well understood. The current study was designed to assess whether attentional control for non-emotional information is impaired in SAD when taking comorbid depression into account. Methods Individuals with SAD and healthy controls (HCs) were administered an attentional blink (AB) task in which they identified number targets in a rapid serial visual presentation stream of letters. Results Individuals with SAD and current comorbid depression exhibited reduced accuracy to identify a target that fell within the AB window after the presentation of a first target compared to individuals with SAD without current comorbid depression, as well as to HCs. The latter two groups did not differ from each other, and the three groups did not differ in accuracy for the second target when it was presented after the AB window. Limitations Although we included two clinical groups and the sample size for the noncomorbid SAD group was large, the comorbid SAD group was relatively small. Conclusions These results suggest that impaired attentional control among individuals with SAD may be limited to those suffering from current comorbid depression. PMID:26370394

  4. Expanded Target-Chemical Analysis Reveals Extensive Mixed-Organic-Contaminant Exposure in U.S. Streams.

    PubMed

    Bradley, Paul M; Journey, Celeste A; Romanok, Kristin M; Barber, Larry B; Buxton, Herbert T; Foreman, William T; 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

    2017-05-02

    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. Log 10 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: < 0.001-0.012), providing a statistical inference tool for unmonitored contaminants. Due to multiple modes of action, high bioactivity, biorecalcitrance, and direct 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 .

  5. Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

    PubMed

    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.

  6. Promoting Social Communication in a Child with Specific Language Impairment

    ERIC Educational Resources Information Center

    O'Handley, Roderick D.; Radley, Keith C.; Lum, John D. K.

    2016-01-01

    Social difficulties represent a major area of concern in children with specific language impairment (SLI). Social skills interventions targeting communication or language skills of children with SLI have been generally ineffective. The current study tested the efficacy of a social skills intervention consisting of multiple behavioral interventions…

  7. Application of technology to social communication impairment in childhood and adolescence.

    PubMed

    Wieckowski, Andrea Trubanova; White, Susan W

    2017-03-01

    Social communication impairment has been implicated in various mental health disorders. The primary aim of this review paper is to summarize the extant research on the development and application of technologies to address social communication deficits, conceptualized according to the four constructs outlined by the NIMH's Research Domain Criteria (RDoC), transdiagnostically in children and adolescents. An exhaustive and systematic search yielded 69 peer-reviewed articles meeting all inclusion criteria (i.e., used technology, applied the technology to target impairment in at least one of four constructs of social communication, included a child or adolescent samples). We found limited use of technology for exploration of impairment in reception of non-facial communication, compared to the other social communication constructs. In addition, there has been an overwhelming focus on social communication impairment in children and adolescents with Autism Spectrum Disorder (ASD), with relatively few studies evaluating technology application in other clinical populations. Implications for future directions for technological interventions to treat social communication impairments transdiagnostically are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Influence of visual impairment and hearing impairment on functional dependence status among people in Taiwan-An evaluation using the WHODAS 2.0 score.

    PubMed

    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.

  9. Cognitive Impairment in Acquired Brain Injury: A Predictor of Rehabilitation Outcomes and an Opportunity for Novel Interventions

    PubMed Central

    Whyte, Ellen; Skidmore, Elizabeth; Aizenstein, Howard; Ricker, Joseph; Butters, Meryl

    2015-01-01

    Cognitive impairment is a common sequela in acquired brain injury and one that predicts rehabilitation outcomes. There is emerging evidence that impairments in cognitive functions can be manipulated by both pharmacologic and nonpharmacologic interventions to improve rehabilitation outcomes. By using stroke as a model for acquired brain injury, we review the evidence that links cognitive impairment to poor rehabilitation outcomes and discuss possible mechanisms to explain this association. Furthermore, we examine nascent promising research that suggests that interventions that target cognitive impairments can lead to better rehabilitation outcomes. PMID:21703580

  10. Rescue of impaired sociability and anxiety-like behavior in adult cacna1c-deficient mice by pharmacologically targeting eIF2α

    PubMed Central

    Kabir, ZD; Che, A; Fischer, DK; Rice, RC; Rizzo, BK; Byrne, M; Glass, MJ; De Marco Garcia, NV; Rajadhyaksha, AM

    2018-01-01

    CACNA1C, encoding the Cav1.2 subunit of L-type Ca2+ channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1.2 signaling may contribute to neuropsychiatric-related disease symptoms via impaired PFC function. Here, we show that mice harboring loss of cacna1c in excitatory glutamatergic neurons of the forebrain (fbKO) that we have previously reported to exhibit anxiety-like behavior, displayed a social behavioral deficit and impaired learning and memory. Furthermore, focal knockdown of cacna1c in the adult PFC recapitulated the social deficit and elevated anxiety-like behavior, but not the deficits in learning and memory. Electrophysiological and molecular studies in the PFC of cacna1c fbKO mice revealed higher E/I ratio in layer 5 pyramidal neurons and lower general protein synthesis. This was concurrent with reduced activity of mTORC1 and its downstream mRNA translation initiation factors eIF4B and 4EBP1, as well as elevated phosphorylation of eIF2α, an inhibitor of mRNA translation. Remarkably, systemic treatment with ISRIB, a small molecule inhibitor that suppresses the effects of phosphorylated eIF2α on mRNA translation, was sufficient to reverse the social deficit and elevated anxiety-like behavior in adult cacna1c fbKO mice. ISRIB additionally normalized the lower protein synthesis and higher E/I ratio in the PFC. Thus this study identifies a novel Cav1.2 mechanism in neuropsychiatric-related endophenotypes and a potential future therapeutic target to explore. PMID:28584287

  11. The neural correlates of impaired inhibitory control in anxiety.

    PubMed

    Ansari, Tahereh L; Derakshan, Nazanin

    2011-04-01

    According to Attentional Control Theory (Eysenck et al., 2007) anxiety impairs the inhibition function of working memory by increasing the influence of stimulus-driven processes over efficient top-down control. We investigated the neural correlates of impaired inhibitory control in anxiety using an antisaccade task. Low- and high-anxious participants performed anti- and prosaccade tasks and electrophysiological activity was recorded. Consistent with previous research high-anxious individuals had longer antisaccade latencies in response to the to-be-inhibited target, compared with low-anxious individuals. Central to our predictions, high-anxious individuals showed lower ERP activity, at frontocentral and central recording sites, than low anxious individuals, in the period immediately prior to onset of the to-be-inhibited target on correct antisaccade trials. Our findings indicate that anxiety interferes with the efficient recruitment of top-down mechanisms required for the suppression of prepotent responses. Implications are discussed within current models of attentional control in anxiety (Bishop, 2009; Eysenck et al., 2007). Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Role of Galectin-3 in Obesity and Impaired Glucose Homeostasis

    PubMed Central

    Menini, Stefano; Iacobini, Carla; Blasetti Fantauzzi, Claudia; Pesce, Carlo M.; Pugliese, Giuseppe

    2016-01-01

    Galectin-3 is an important modulator of several biological functions. It has been implicated in numerous disease conditions, particularly in the long-term complications of diabetes because of its ability to bind the advanced glycation/lipoxidation end products that accumulate in target organs and exert their toxic effects by triggering proinflammatory and prooxidant pathways. Recent evidence suggests that galectin-3 may also participate in the development of obesity and type 2 diabetes. It has been shown that galectin-3 levels are higher in obese and diabetic individuals and parallel deterioration of glucose homeostasis. Two studies in galectin-3 knockout mice fed a high-fat diet (HFD) have shown increased adiposity and adipose tissue and systemic inflammation associated with altered glucose homeostasis, suggesting that galectin-3 negatively modulates the responsiveness of innate and adaptive immunity to overnutrition. However, these studies have also shown that impaired glucose homeostasis occurs in galectin-3 knockout animals independently of obesity. Moreover, another study reported decreased weight and fat mass in HFD-fed galectin-3 knockout mice. In vitro, galectin-3 was found to stimulate differentiation of preadipocytes into mature adipocytes. Altogether, these data indicate that galectin-3 deserves further attention in order to clarify its role as a potential player and therapeutic target in obesity and type 2 diabetes. PMID:26770660

  13. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

    PubMed

    Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

    2014-01-01

    Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference "Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms" convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants.

  14. Isoflurane Impairs Low-Frequency Feedback but Leaves High-Frequency Feedforward Connectivity Intact in the Fly Brain.

    PubMed

    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.

  15. Isoflurane Impairs Low-Frequency Feedback but Leaves High-Frequency Feedforward Connectivity Intact in the Fly Brain

    PubMed Central

    2018-01-01

    Abstract 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. PMID:29541686

  16. Impaired working memory capacity is not caused by failures of selective attention in schizophrenia.

    PubMed

    Erickson, Molly A; Hahn, Britta; Leonard, Carly J; Robinson, Benjamin; Gray, Brad; Luck, Steven J; Gold, James

    2015-03-01

    The cognitive impairments associated with schizophrenia have long been known to involve deficits in working memory (WM) capacity. To date, however, the causes of WM capacity deficits remain unknown. The present study examined selective attention impairments as a putative contributor to observed capacity deficits in this population. To test this hypothesis, we used an experimental paradigm that assesses the role of selective attention in WM encoding and has been shown to involve the prefrontal cortex and the basal ganglia. In experiment 1, participants were required to remember the locations of 3 or 5 target items (red circles). In another condition, 3-target items were accompanied by 2 distractor items (yellow circles), which participants were instructed to ignore. People with schizophrenia (PSZ) exhibited significant impairment in memory for the locations of target items, consistent with reduced WM capacity, but PSZ and healthy control subjects did not differ in their ability to filter the distractors. This pattern was replicated in experiment 2 for distractors that were more salient. Taken together, these results demonstrate that reduced WM capacity in PSZ is not attributable to a failure of filtering irrelevant distractors. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

    PubMed

    Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

    2018-01-01

    Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  < 0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

  18. Evidence-based guidelines on the referral of visually impaired persons to low vision services.

    PubMed

    De Boer, M R; Langelaan, M; Jansonius, N M; Van Rens, G H M B

    2005-01-01

    One to two percent of the population in the Western world is visually impaired or blind. For most of these people there is no curative therapy. Therefore, the Dutch Ophthalmic Society has taken the initiative to develop an evidence-based guideline for the referral of visually impaired persons to low vision services. A systematic literature search was performed in the Embase (1991-2001) and Medline (1966-2003) databases. Literature was searched for definitions of visual impairment, for physician-patient communication, and for outcome of interventions for visually impaired persons. Results of the articles that were selected were summarized and rated according to the level of evidence. Other considerations such as the current organization of rehabilitation for visually impaired persons in the Netherlands were also taken into account. The World Health Organization criteria were slightly adapted in order to include all people who experience problems with reading and other daily life activities due to visual impairment. A large number of recommendations were devised. Among these is that the complete diagnosis should be communicated to the patient and that a second appointment should be offered in which the diagnosis and potential treatment options are discussed again. Another recommendation is that in general visually impaired adults eligible for referral should be referred for the provision of low vision aids and that patients with complex problems or extensive rehabilitative demand should be referred to a rehabilitation center. This article presents a summary of the first European evidence-based guideline for the referral of visually impaired persons.

  19. The potential dysfunction of otolith organs in patients after mumps infection

    PubMed Central

    Tian, Liang; Han, Zhao; Wang, Jing; Chi, Fang-Lu

    2017-01-01

    Objective To investigate the relationship between mumps and the extent of hearing impairment and otolith organ damage. Methods A total of 27 patients with unilateral hearing impairment following mumps were enrolled. The degrees of hearing loss and otolith organ damage were confirmed by audiometric and vestibular evoked myogenic potential [VEMP] tests. All the results were compared and analyzed using Stata 13.0 software for Windows. Results The VEMP thresholds of the affected ears were significantly higher than those of the unaffected ears in both tests (cervical VEMP [cVEMP] test and ocular VEMP [oVEMP] test; p = 0.000 and 0.001, respectively). The mean cVEMP and oVEMP threshold values of the affected ears with hearing impairment for ≤10 years were significantly lower than those of affected ears with hearing impairment for >10 years [p = 0.009 and 0.004, respectively]. Conclusions Deafness resulting from mumps is usually profound and permanent, which indicates severe damage to the cochlea due to the disease. The functions of otolith organs in the vestibular system are also impaired. Over time, the function of the otolith organs or their neural pathway may suffer secondary damage. PMID:28746415

  20. Office and 24-hour heart rate and target organ damage in hypertensive patients

    PubMed Central

    2012-01-01

    Background We investigated the association between heart rate and its variability with the parameters that assess vascular, renal and cardiac target organ damage. Methods A cross-sectional study was performed including a consecutive sample of 360 hypertensive patients without heart rate lowering drugs (aged 56 ± 11 years, 64.2% male). Heart rate (HR) and its standard deviation (HRV) in clinical and 24-hour ambulatory monitoring were evaluated. Renal damage was assessed by glomerular filtration rate and albumin/creatinine ratio; vascular damage by carotid intima-media thickness and ankle/brachial index; and cardiac damage by the Cornell voltage-duration product and left ventricular mass index. Results There was a positive correlation between ambulatory, but not clinical, heart rate and its standard deviation with glomerular filtration rate, and a negative correlation with carotid intima-media thickness, and night/day ratio of systolic and diastolic blood pressure. There was no correlation with albumin/creatinine ratio, ankle/brachial index, Cornell voltage-duration product or left ventricular mass index. In the multiple linear regression analysis, after adjusting for age, the association of glomerular filtration rate and intima-media thickness with ambulatory heart rate and its standard deviation was lost. According to the logistic regression analysis, the predictors of any target organ damage were age (OR = 1.034 and 1.033) and night/day systolic blood pressure ratio (OR = 1.425 and 1.512). Neither 24 HR nor 24 HRV reached statistical significance. Conclusions High ambulatory heart rate and its variability, but not clinical HR, are associated with decreased carotid intima-media thickness and a higher glomerular filtration rate, although this is lost after adjusting for age. Trial Registration ClinicalTrials.gov: NCT01325064 PMID:22439900

  1. Application of the target lipid model and passive samplers to characterize the toxicity of bioavailable organics in oil sands process-affected water.

    PubMed

    Redman, Aaron D; Parkerton, Thomas F; Butler, Josh David; Letinski, Daniel J; Frank, Richard A; Hewitt, L Mark; Bartlett, Adrienne J; Gillis, Patricia Leigh; Marentette, Julie R; Parrott, Joanne L; Hughes, Sarah A; Guest, Rodney; Bekele, Asfaw; Zhang, Kun; Morandi, Garrett; Wiseman, Steve B; Giesy, John P

    2018-06-14

    Oil sand operations in Alberta, Canada will eventually include returning treated process-affected waters to the environment. Organic constituents in oil sand process-affected water (OSPW) represent complex mixtures of nonionic and ionic (e.g. naphthenic acids) compounds, and compositions can vary spatially and temporally, which has impeded development of water quality benchmarks. To address this challenge, it was hypothesized that solid phase microextraction fibers coated with polydimethylsiloxane (PDMS) could be used as a biomimetic extraction (BE) to measure bioavailable organics in OSPW. Organic constituents of OSPW were assumed to contribute additively to toxicity, and partitioning to PDMS was assumed to be predictive of accumulation in target lipids, which were the presumed site of action. This method was tested using toxicity data for individual model compounds, defined mixtures, and organic mixtures extracted from OSPW. Toxicity was correlated with BE data, which supports the use of this method in hazard assessments of acute lethality to aquatic organisms. A species sensitivity distribution (SSD), based on target lipid model and BE values, was similar to SSDs based on residues in tissues for both nonionic and ionic organics. BE was shown to be an analytical tool that accounts for bioaccumulation of organic compound mixtures from which toxicity can be predicted, with the potential to aid in the development of water quality guidelines.

  2. [Epidemiological survey of visual impairment in Funing County, Jiangsu].

    PubMed

    Yang, M; Zhang, J F; Zhu, R R; Kang, L H; Qin, B; Guan, H J

    2017-07-11

    Objective: To investigate the prevalence of visual impairment and factors associated with visual impairment among people aged 50 years and above in Funing County, Jiangsu Province. Methods: Cross-sectional study. Random cluster sampling was used in selecting individuals aged ≥50 years in 30 clusters, and 5 947 individuals received visual acuity testing and eye examination. Stata 13.0 software was used to analyze the data. Multivariate logistic regression was used to detect possible factors of visual impairment such as age, gender and education. Statistical significance was defined as P< 0.05. Results: A total of 6 145 persons aged 50 years and above were enumerated, and 5 947 (96.8%) participants were examined. Based on the criteria of World Health Organization (WHO) visual impairment classification and presenting visual acuity, 138 persons were diagnosed as blindness, and 1 405 persons were diagnosed as low vision. The prevalence of blindness and low vision was 2.32% and 23.63%, respectively. And the prevalence of visual impairment was 25.95%. Based on the criteria of WHO visual impairment classification and best-corrected visual acuity, 92 persons were diagnosed as blindness, and 383 persons were diagnosed as low vision. The prevalence of blindness and low vision was 1.55% and 6.44%, respectively. And the prevalence of visual impairment was 7.99%. Concerning presenting visual acuity and best-corrected visual acuity, the prevalence of blindness and low vision was higher in old people, females and less educated persons. Cataract (46.63%) was the leading cause of blindness. Uncorrected refractive error (36.51%) was also a main cause of visual impairment. Conclusion: The prevalence of visual impairment is higher in old people, females and less educated persons in Funing County, Jiangsu Province. Cataract is still the leading cause of visual impairment. (Chin J Ophthalmol, 2017, 53: 502-508) .

  3. Proportional Recovery From Lower Limb Motor Impairment After Stroke.

    PubMed

    Smith, Marie-Claire; Byblow, Winston D; Barber, P Alan; Stinear, Cathy M

    2017-05-01

    In people with preserved corticospinal tract (CST) function after stroke, upper limb impairment resolves by ≈70% within 3 months. This is known as the proportional recovery rule. Patients without CST function do not fit this rule and have worse upper limb outcomes. This study investigated resolution of motor impairment in the lower limb (LL). Patients with stroke and LL weakness were assessed 3 days and 3 months after stroke with the LL Fugl-Meyer. CST integrity was determined in a subset of patients using transcranial magnetic stimulation to test for LL motor-evoked potentials and magnetic resonance imaging to measure CST lesion load. Linear regression analyses were conducted to predict resolution of motor impairment (ΔFugl-Meyer) including factors initial impairment, motor-evoked potential status, CST lesion load, and LL therapy dose. Thirty-two patients completed 3-month follow-up and recovered 74% (95% confidence interval, 60%-88%) of initial LL motor impairment. Initial impairment was the only significant predictor of resolution of motor impairment. There was no identifiable cluster of patients who did not fit the proportional recovery rule. Measures of CST integrity did not predict proportional LL recovery. LL impairment resolves by ≈70% within 3 months after stroke. The absence of a nonfitter group may be because of differences in the neuroanatomical organization of descending motor tracts to the upper limb and LL. Proportional recovery of the LL is not influenced by therapy dose providing further evidence that it reflects a fundamental biological process. © 2017 American Heart Association, Inc.

  4. A framework for communication between visually impaired, hearing impaired and speech impaired using arduino

    NASA Astrophysics Data System (ADS)

    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.

  5. Novel targets for ATM-deficient malignancies

    PubMed Central

    Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

    2014-01-01

    Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

  6. Toxicity of the bionematicide 1,4-naphthoquinone on non-target soil organisms.

    PubMed

    Chelinho, S; Maleita, C M N; Francisco, R; Braga, M E M; da Cunha, M J M; Abrantes, I; de Sousa, H C; Morais, P V; Sousa, J P

    2017-08-01

    The main goal of the present study was to evaluate the ecotoxicological effects of 1,4-naphthoquinone (1,4-NTQ), a natural-origin compound presenting nematicidal activity, that can be obtained from walnut husk, in plants and soil invertebrates, including non-target soil nematode communities. This research was part of an ongoing project that aims to develop environmentally-friendly nematicides obtained from agricultural residues. The battery of ISO tests included emergence and growth of corn (Zea mays) and rape (Brassica napus); avoidance with the earthworm Eisenia andrei and the collembolan Folsomia candida; and reproduction with the previous species plus the enchytraeid Enchytraeus crypticus. A novel soil nematode community assay was also performed. ISO tests and nematode assays were conducted using a natural uncontaminated soil that was spiked with a range of 1,4-NTQ concentrations. Toxicity of 1,4-NTQ was found for all test-species and the most sensitive were F. candida and E. andrei. After 7 days of exposure to 1,4-NTQ, nematode abundance decreased along the concentration gradient, and a partial recovery was observed after 14 days (1,4-NTQ <48 mg kg -1 soil). The number of nematode families consistently decreased in both periods. Overall, results indicate that a 1,4-NTQ concentration of <20 mg kg -1 could be environmentally safe but preliminary data suggest that it might be ineffective for the target-nematodes, root-knot nematodes, Meloidogyne spp., and root-lesion nematodes, Pratylenchus spp. In addition, if higher dosages of 1,4-NTQ bionematicide are necessary, the potential recovery of non-target organisms under real field scenarios also needs to be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Ambulatory and home blood pressure monitoring in children and adolescents: diagnosis of hypertension and assessment of target-organ damage.

    PubMed

    Karpettas, Nikos; Nasothimiou, Efthimia; Kollias, Anastasios; Vazeou, Adriani; Stergiou, George S

    2013-04-01

    The prevalence of elevated blood pressure in children and adolescents is more common than previously believed and often represents the early onset of essential hypertension, particularly in adolescents. The definition of hypertension in children is based on distribution criteria and normalcy tables that provide blood pressure percentiles for each measurement method (office, ambulatory and home) according to the individual's age, gender and body size. Owing to the white coat and masked hypertension phenomena, ambulatory blood pressure monitoring is indispensable for the diagnosis of hypertension in children. Home blood pressure monitoring in children has been less well studied, and at present, treatment decisions should not be based solely on such measurements. Hypertension-induced preclinical target-organ damage (mainly echocardiographic left ventricular hypertrophy) is not uncommon in children and should be evaluated in all hypertensive children. Other indices of target-organ damage, such as carotid intima-media thickness, pulse wave velocity and microalbuminuria, remain under investigation in pediatric hypertension.

  8. Non-target screening analyses of organic contaminants in river systems as a base for monitoring measures

    NASA Astrophysics Data System (ADS)

    Schwarzbauer, J.

    2009-04-01

    Organic contaminants discharged to the aquatic environment exhibit a high diversity with respect to their molecular structures and the resulting physico-chemical properties. The chemical analysis of anthropogenic contamination in river systems is still an important feature, especially with respect to (i) the identification and structure elucidation of novel contaminants, (ii) to the characterisation of their environmental behaviour and (iii) to their risk for natural systems. A huge proportion of riverine contamination is caused by low-molecular weight organic compounds, like pesticides plasticizers, pharmaceuticals, personal care products, technical additives etc. Some of them, like PCB or PAH have already been investigated thoroughly and, consequently, their behaviour in aqueous systems is very well described. Although analyses on organic substances in river water traditionally focused on selected pollutants, in particular on common priority pollutants which are monitored routinely, the occurrence of further contaminants, e.g. pharmaceuticals, personal care products or chelating agents has received increasing attention within the last decade. Accompanied, screening analyses revealing an enormous diversity of low-molecular weight organic contaminants in waste water effluents and river water become more and more noticed. Since many of these substances have been rarely noticed so far, it will be an important task for the future to study their occurrence and fate in natural environments. Further on, it should be a main issue of environmental studies to provide a comprehensive view on the state of pollution of river water, in particular with respect to lipophilic low molecular weight organic contaminants. However, such non-target-screening analyses has been performed only rarely in the past. Hence, we applied extended non-target screening analyses on longitudinal sections of the rivers Rhine, Rur and Lippe (Germany) on the base of GC/MS analyses. The investigations

  9. Age-Related Impairment on a Forced-Choice Version of the Mnemonic Similarity Task

    PubMed Central

    Huffman, Derek J.; Stark, Craig E. L.

    2018-01-01

    Previous studies from our lab have indicated that healthy older adults are impaired in their ability to mnemonically discriminate between previously viewed objects and similar lure objects in the Mnemonic Similarity Task (MST). These studies have used either old/similar/new or old/new test formats. The forced-choice test format (e.g., “Did you see object A or object A’ during the encoding phase?”) relies on different assumptions than the old/new test format (e.g., “Did you see this object during the encoding phase?”); hence, converging evidence from these approaches would bolster the conclusion that healthy aging is accompanied by impaired performance on the MST. Consistent with our hypothesis, healthy older adults exhibited impaired performance on a forced-choice test format that required discriminating between a target and a similar lure. We also tested the hypothesis that age-related impairments on the MST could be modeled within a global matching computational framework. We found that decreasing the probability of successful feature encoding in the models caused changes that were similar to the empirical data in healthy older adults. Collectively, our behavioral results extend to the forced-choice test format the finding that healthy aging is accompanied by an impaired ability to discriminate between targets and similar lures, and our modeling results suggest that a diminished probability of encoding stimulus features is a candidate mechanism for memory changes in healthy aging. We also discuss the ability of global matching models to account for findings in other studies that have used variants on mnemonic similarity tasks. PMID:28004951

  10. Adaptation of Psychological Assessment Tools for Administration by Blind and Visually Impaired Psychologists and Trainees.

    ERIC Educational Resources Information Center

    Keller, Richard M.

    This paper focuses on challenges to psychologists and psychology graduate students who are blind or visually impaired in the administration and scoring of various psychological tests. Organized by specific tests, the paper highlights those aspects of testing which pose particular difficulty to testers with visual impairments and also describes…

  11. How Should DSM-V Criteria for Schizophrenia Include Cognitive Impairment?

    PubMed Central

    Keefe, Richard S. E.; Fenton, Wayne S.

    2007-01-01

    Neurocognitive impairment is considered a core component of schizophrenia and is increasingly under investigation as a potential treatment target. On average, cognitive impairment is severe to moderately severe compared with healthy controls, and almost all patients with schizophrenia demonstrate cognitive decrements compared with their expected level if they had not developed the illness. Compared with patients with affective disorders, cognitive impairment in schizophrenia appears earlier, is more severe, and tends to be more independent of clinical symptoms. While the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, description of schizophrenia includes several references to cognitive impairment, neither the diagnostic criteria nor the subtypology of schizophrenia include a requirement of cognitive impairment. We forward for consideration a proposal that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria include a specific criterion of “a level of cognitive functioning suggesting a consistent severe impairment and/or a significant decline from premorbid levels considering the patient's educational, familial, and socioeconomic background.” The inclusion of this criterion may increase the “point of rarity” with affective psychoses and may increase clinicians' awareness of cognitive impairment, potentially leading to more accurate prognosis and better treatment outcomes. Future research will need to address the validity of these possibilities. The reliable determination of cognitive impairment as part of a standard diagnostic evaluation may present challenges to diagnosticians with limited resources or insufficient expertise. Various cognitive assessment methods for clinicians, including brief assessments and interview-based assessments, are discussed. Given the current emphasis on the development of cognitive treatments, the evaluation of cognition in schizophrenia is an essential

  12. Cognitive Function as a Trans-Diagnostic Treatment Target in Stimulant Use Disorders

    PubMed Central

    Sofuoglu, Mehmet; DeVito, Elise E.; Waters, Andrew J.; Carroll, Kathleen M.

    2016-01-01

    Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration (FDA) for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder, and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% - 73%, with the most common being mood disorders (13% - 64%) and anxiety disorders (21% - 50%), as well as non-substance induced psychotic disorders (under 10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder, and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible trans-diagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive

  13. Covalent Ligand Discovery against Druggable Hotspots Targeted by Anti-cancer Natural Products.

    PubMed

    Grossman, Elizabeth A; Ward, Carl C; Spradlin, Jessica N; Bateman, Leslie A; Huffman, Tucker R; Miyamoto, David K; Kleinman, Jordan I; Nomura, Daniel K

    2017-11-16

    Many natural products that show therapeutic activities are often difficult to synthesize or isolate and have unknown targets, hindering their development as drugs. Identifying druggable hotspots targeted by covalently acting anti-cancer natural products can enable pharmacological interrogation of these sites with more synthetically tractable compounds. Here, we used chemoproteomic platforms to discover that the anti-cancer natural product withaferin A targets C377 on the regulatory subunit PPP2R1A of the tumor-suppressor protein phosphatase 2A (PP2A) complex leading to activation of PP2A activity, inactivation of AKT, and impaired breast cancer cell proliferation. We developed a more synthetically tractable cysteine-reactive covalent ligand, JNS 1-40, that selectively targets C377 of PPP2R1A to impair breast cancer signaling, proliferation, and in vivo tumor growth. Our study highlights the utility of using chemoproteomics to map druggable hotspots targeted by complex natural products and subsequently interrogating these sites with more synthetically tractable covalent ligands for cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Audiology in Latin America: hearing impairment, resources and services.

    PubMed

    Madriz, J J

    2001-01-01

    Evidence is presented about the limitation of information available on prevalence/incidence of deafness and hearing impairment in the developing world; particularly in Latin America. Two questionnaires on audiological resources and services were mailed to Latin American and Caribbean countries in general and to Central American nations in particular. The information returned by Argentina, Chile, Colombia, Costa Rica, Cuba, Belize, El Salvador, Grenada, Guatemala, Honduras, Mexico, Nicaragua, Panama, Puerto Rico and Uruguay was analysed. Data was gathered about epidemiological studies on hearing impairment, about specific programmes, such as early identification of hearing impairment, national registers on deafness and programmes on hearing screening. Training programmes and availability of professionals in the field of hearing and deafness is also shown. Hearing services, hearing aids provision, hearing testing equipment, professional organization and legislation in audiology is also documented. It is our conclusion that hearing impairment is a low priority for health systems in the developing world, technology continues to be excessively costly and material and human resources are limited, and services are poor and restricted.

  15. The prevalence of hearing impairment within the Cape Town Metropolitan area

    PubMed Central

    Ramma, Lebogang

    2016-01-01

    Background There is a lack of data on the prevalence of hearing impairment in South Africa. Current data is unreliable as it is based on national census information which tends to underestimate the prevalence of hearing impairment. Aim The aim of this study was to estimate the prevalence of hearing impairment in the Cape Town Metropolitan area and to determine factors associated with hearing impairment. Method A cross-sectional household survey involving 2494 partcipants from 718 households was conducted between the months of February and October 2013. Random cluster sampling was used to select four health sub-districts from eight health sub-districts in the Cape Town Metropolitan area using a method of probability proportional to size (PPS). The survey was conducted according to the World Health Organization (WHO) Ear and Hearing Disorders Survey Protocol and the classifcation of hearing impairment matched the WHO’s criteria for the grading of hearing impairment. Results The overall prevalence of hearing impairment in the population of this study was 12.35% (95% CI: 11.06% – 13.64%) and prevalence of disabling hearing impairment was 4.57% (95% CI: 3.75% – 5.39%) amongst individuals ≥ 4 years old. The following factors were found to be associated with hearing impairment; male gender, age, hypertension, a history of head and neck trauma and a family history of hearing impairment. Conclusion Based on the data from communities surveyed during this study, hearing impairment is more prevalent than previously estimated based on national population census information. Interventions for the prevention of hearing impairment in these communities should focus on individuals with associated risk factors. PMID:27247255

  16. 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.

    PubMed

    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 trend<0.05). Vision was significantly related to LS (r=0.238, p<0.001), PA (r=0.142, p<0.01), NA (r=-0.157, p<0.001), and AB (r=0.206, p<0.001). After adjustment for multiple variables including functional ability, an important factor of SWB, the associations of vision impairment 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.

  17. Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

    PubMed Central

    Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

    2012-01-01

    Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

  18. Multiple Learning Strategies Project. Small Engine Repair. Visually Impaired.

    ERIC Educational Resources Information Center

    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…

  19. Association Between Sensory Impairment and Dementia in Older Adults: Evidence from China.

    PubMed

    Luo, Yanan; He, Ping; Guo, Chao; Chen, Gong; Li, Ning; Zheng, Xiaoying

    2018-03-01

    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 <0.05, visual field less than 10 degrees; the better-seeing eye). The prevalence of 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.

  20. [The problems of hearing impairment in the flying staff of commercial aviation in Russia].

    PubMed

    Pankova, V B; Bushmanov, A Iu

    2014-01-01

    The authors discuss the problems pertaining to the growing incidence of hearing impairment in the members of the flying staff employed in commercial aviation of Russia and the main criteria used to elucidate the causes behind occupational diseases of the organs of hearing. Special attention is given to the principal normative documents regulating the methodological basis on which the acoustic factor in the aircraft cockpit is evaluated, peculiarities of occupational sensorineural hearing impairment and the methods for its detection. The main errors in the determination of the relationship between the working conditions and the diseases of the organs of hearing are discussed.

  1. Traumatic brain injury impairs small-world topology

    PubMed Central

    Pandit, Anand S.; Expert, Paul; Lambiotte, Renaud; Bonnelle, Valerie; Leech, Robert; Turkheimer, Federico E.

    2013-01-01

    Objective: We test the hypothesis that brain networks associated with cognitive function shift away from a “small-world” organization following traumatic brain injury (TBI). Methods: We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging. Results: Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics. Conclusions: We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI. PMID:23596068

  2. [Prevalence of target organ damage and metabolic abnormalities in resistant hypertension].

    PubMed

    Armario, Pedro; Oliveras, Anna; Hernández Del Rey, Raquel; Ruilope, Luis Miguel; De La Sierra, Alejandro

    2011-10-15

    Patients with resistant hypertension (RH) are relatively frequently visited in specialized units of hypertension. The aim of this study was to assess the prevalence of target organ damage, central obesity and metabolic syndrome in a cohort of patients with RH consecutively included in the Register of Resistant Hypertension of the Spanish Society of Hypertension (SHE-LELHA). Cross-sectional, multicenter epidemiologic study in usual clinical practice conditions. Patients with clinical diagnosis of resistant hypertension, that is, office systolic and diastolic blood pressure ≥ 140 mm Hg and/or ≥ 90 mm Hg, respectively, despite a prescribed therapeutic schedule with an appropriate combination of three or more full-dose antihypertensive drugs, including a diuretic, were consecutively recruited from specialized hypertension units spread through Spain. Demographic and anthropometric characteristics as well as cardiovascular risk factors and associated conditions were recorded, and all the subjects underwent 24-h ambulatory blood pressure monitoring. Left ventricular hypertrophy was considered as a left ventricular mass index ≥ 125 g/m(2) in males and ≥ 110 g/m(2) in females. Left atrial enlargement was defined as an indexed left atrium diameter ≥ 26 mm/m(2). Microalbuminuria was defined as a urinary albumin/creatinine ratio ≥ 22 mg/g in males and ≥ 31 mg/g in females. 513 patients were included, aged 64±11 years old, 47% women. Central obesity was present in 65.7% (CI 95% 61.6-69.9), 38.6% (CI 95% 34.4-42.8) had diabetes and 63.7% (CI 95% 59.4-67.9) had metabolic syndrome. The prevalence of left ventricular hypertrophy and left atrial enlargement, determined by echocardiography was 57.1% (CI 95% 50.8-63.5) and 10.0% (CI 95% 6.3-13.7) respectively. Microalbuminuria was found in 46.6% (CI 95% 41.4-51.8) of the subjects. Patients with metabolic syndrome were significantly older (65.4±11 and 62.5±12 years; P=.0052), presented a higher prevalence of diabetes

  3. Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis.

    PubMed

    Cao, Zhongwei; Ye, Tinghong; Sun, Yue; Ji, Gaili; Shido, Koji; Chen, Yutian; Luo, Lin; Na, Feifei; Li, Xiaoyan; Huang, Zhen; Ko, Jane L; Mittal, Vivek; Qiao, Lina; Chen, Chong; Martinez, Fernando J; Rafii, Shahin; Ding, Bi-Sen

    2017-08-30

    The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts establishes "hospitable soil" to foster the incorporation of "seed," in this case, the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NOX4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 4] synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs ( Hgf iΔEC/iΔEC ) aberrantly up-regulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in Hgf iΔEC/iΔEC mice recapitulated the phenotype of human and mouse liver and lung fibrosis. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  4. Sample Analysis at Mars (SAM) and Mars Organic Molecule Analyzer (MOMA) as Critical In Situ Investigation for Targeting Mars Returned Samples

    NASA Astrophysics Data System (ADS)

    Freissinet, C.; Glavin, D. P.; Mahaffy, P. R.; Szopa, C.; Buch, A.; Goesmann, F.; Goetz, W.; Raulin, F.; SAM Science Team; MOMA Science Team

    2018-04-01

    SAM (Curiosity) and MOMA (ExoMars) Mars instruments, seeking for organics and biosignatures, are essential to establish taphonomic windows of preservation of molecules, in order to target the most interesting samples to return from Mars.

  5. Development of voice navigation system for the visually impaired by using IC tags.

    PubMed

    Takatori, Norihiko; Nojima, Kengo; Matsumoto, Masashi; Yanashima, Kenji; Magatani, Kazushige

    2006-01-01

    There are about 300,000 visually impaired persons in Japan. Most of them are old persons and, cannot become skillful in using a white cane, even if they make effort to learn how to use a white cane. Therefore, some guiding system that supports the independent activities of the visually impaired are required. In this paper, we will describe about a developed white cane system that supports the independent walking of the visually impaired in the indoor space. This system is composed of colored navigation lines that include IC tags and an intelligent white cane that has a navigation computer. In our system colored navigation lines that are put on the floor of the target space from the start point to the destination and IC tags that are set at the landmark point are used for indication of the route to the destination. The white cane has a color sensor, an IC tag transceiver and a computer system that includes a voice processor. This white cane senses the navigation line that has target color by a color sensor. When a color sensor finds the target color, the white cane informs a white cane user that he/she is on the navigation line by vibration. So, only following this vibration, the user can reach the destination. However, at some landmark points, guidance is necessary. At these points, an IC tag is set under the navigation line. The cane makes communication with the tag and informs the user about the land mark pint by pre recorded voice. Ten normal subjects who were blindfolded were tested with our developed system. All of them could walk along navigation line. And the IC tag information system worked well. Therefore, we have concluded that our system will be a very valuable one to support activities of the visually impaired.

  6. Temporal Evolution of Poststroke Cognitive Impairment Using the Montreal Cognitive Assessment.

    PubMed

    Nijsse, Britta; Visser-Meily, Johanna M A; van Mierlo, Maria L; Post, Marcel W M; de Kort, Paul L M; van Heugten, Caroline M

    2017-01-01

    The Montreal Cognitive Assessment (MoCA) is nowadays recommended for the screening of poststroke cognitive impairment. However, little is known about the temporal evolution of MoCA-assessed cognition after stroke. The objective of this study was to examine the temporal pattern of overall and domain-specific cognition at 2 and 6 months after stroke using the MoCA and to identify patient groups at risk for cognitive impairment at 6 months after stroke. Prospective cohort study in which 324 patients were administered the MoCA at 2 and 6 months post stroke. Cognitive impairment was defined as MoCA<26. Differences in cognitive impairment rates between 2 and 6 months post stroke were analyzed in different subgroups. Patients with MoCA score <26 at 2 months, who improved by ≥2 points by 6 months, were defined as reverters. Logistic regression analyses were used to identify determinants of (1) cognitive impairment at 6 months post stroke and (2) reverter status. Between 2 and 6 months post stroke, mean MoCA score improved from 23.7 (3.9) to 24.7 (3.5), P<0.001. Prevalence of cognitive impairment at 2 months was 66.4%, compared with 51.9% at 6 months (P<0.001). More comorbidity and presence of cognitive impairment at 2 months were significant independent predictors of cognitive impairment 6 months post stroke. No significant determinants of reverter status were identified. Although cognitive improvement is seen ≤6 months post stroke, long-term cognitive deficits are prevalent. Identifying patients at risk of cognitive impairment is, therefore, important as well as targeting interventions to this group. © 2016 American Heart Association, Inc.

  7. Should cognitive impairment be included in the diagnostic criteria for schizophrenia?

    PubMed

    Keefe, Richard S E

    2008-02-01

    Neurocognitive impairment is considered a core component of schizophrenia, and is increasingly under investigation as a potential treatment target. On average, cognitive impairment is severe to moderately severe compared to healthy controls, and almost all patients with schizophrenia demonstrate cognitive decrements compared to their expected level if they had not developed the illness. Compared to patients with affective disorders, cognitive impairment in schizophrenia appears earlier, is more severe, and is more independent of clinical symptoms. Although the DSM-IV-TR and ICD-10 descriptions of schizophrenia include several references to cognitive impairment, neither the diagnostic criteria nor the subtypology of schizophrenia include a requirement of cognitive impairment. This paper forwards for consideration a proposal that the diagnostic criteria include a specific criterion of "a level of cognitive functioning suggesting a consistent severe impairment and/or a significant decline from premorbid levels considering the patient's educational, familial, and socioeconomic background". The inclusion of this criterion may increase the "point of rarity" with affective psychoses and may increase clinicians' awareness of cognitive impairment, potentially leading to more accurate prognosis, better treatment outcomes, and a clearer diagnostic signal for genetic and biological studies. Future research will need to address the validity of these possibilities. The reliable determination of cognitive impairment as part of a standard diagnostic evaluation will present challenges to diagnosticians with limited resources or insufficient expertise. Cognitive assessment methods for clinicians, including brief assessments and interview-based assessments, are discussed. Given the current emphasis on the development of cognitive treatments, the evaluation of cognition in schizophrenia is an essential component of mental health education.

  8. Childhood visual impairment: normal and abnormal visual function in the context of developmental disability.

    PubMed

    Nyong'o, Omondi L; Del Monte, Monte A

    2008-12-01

    Abnormal or failed development of vision in children may give rise to varying degrees of visual impairment and disability. Disease and organ-specific mechanisms by which visual impairments arise are presented. The presentation of these mechanisms, along with an explanation of established pathologic processes and correlative up-to-date clinical and social research in the field of pediatrics, ophthalmology, and rehabilitation medicine are discussed. The goal of this article is to enhance the practitioner's recognition and care for children with developmental disability associated with visual impairment.

  9. Wound Healing in Patients With Impaired Kidney Function

    PubMed Central

    Maroz, Natallia; Simman, Richard

    2014-01-01

    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. PMID:26199882

  10. Pamphlet Library [for Working with Multihandicapped, Visually-Impaired Individuals].

    ERIC Educational Resources Information Center

    Boston Center for Blind Children, MA.

    The Boston Center for Blind Children has prepared an annotated bibliography of pamphlets intended to be useful to persons working with multiply-handicapped, visually-impaired individuals. The pamphlets are organized under the following categories (number of entries in each category is listed in parentheses): bibliographies (4), epilepsy (4), facts…

  11. Hearing Impairment, Mild Cognitive Impairment, and Dementia: A Meta-Analysis of Cohort Studies.

    PubMed

    Wei, Jingkai; Hu, Yirui; Zhang, Li; Hao, Qiang; Yang, Ruowei; Lu, Haidong; Zhang, Xuan; Chandrasekar, Eeshwar K

    2017-01-01

    To estimate a pooled association between hearing impairment and risk of mild cognitive impairment and dementia. PubMed, Embase, and Web of Science were searched for prospective cohort studies that examined the association between hearing impairment and risk of mild cognitive impairment and/or dementia. Random-effects models were fitted to estimate the summary risk ratios (RRs) and 95% confidence interval (CIs), which represents the pooled association between hearing impairment with risk of mild cognitive impairment and dementia, compared to subjects free of hearing impairment. Four studies on hearing impairment with mild cognitive impairment and 7 studies on hearing impairment with dementia were included in the meta-analysis. A total of 15,521 subjects were studied with follow-up periods between 2 and 16.8 years. Hearing impairment was associated with a greater risk of mild cognitive impairment (RR = 1.30, 95% CI: 1.12, 1.51) and dementia (RR = 2.39, 95% CI: 1.58, 3.61). The meta-analysis showed that hearing impairment is associated with a higher risk of mild cognitive impairment and dementia among older adults.

  12. Functional impairment and hospital readmission in Medicare seniors.

    PubMed

    Greysen, S Ryan; Stijacic Cenzer, Irena; Auerbach, Andrew D; Covinsky, Kenneth E

    2015-04-01

    ADL (OR, 1.08; 95% CI, 0.96-1.21), 16.5% with dependency in 1 to 2 ADLs (OR, 1.26; 95% CI, 1.11-1.44), and 18.2% with dependency in 3 or more ADLs (OR, 1.42; 95% CI, 1.20-1.69). Subanalysis restricted to patients admitted with conditions targeted by Medicare (ie, heart failure, myocardial infarction, and pneumonia) revealed a parallel trend with larger effects for the most impaired (16.9% readmission rate for no impairment vs 25.7% for dependency in 3 or more ADLs [OR, 1.70; 95% CI, 1.04-2.78]). Functional impairment is associated with increased risk of 30-day all-cause hospital readmission in Medicare seniors, especially those admitted for heart failure, myocardial infarction, or pneumonia. Functional impairment may be an important but underaddressed factor in preventing readmissions for Medicare seniors.

  13. Participation in Physical Play and Leisure in Children With Motor Impairments: Mixed-Methods Study to Generate Evidence for Developing an Intervention

    PubMed Central

    Ramsay, Craig; McKee, Lorna; Missiuna, Cheryl; Owen, Christine; Francis, Jill

    2015-01-01

    Background Participation in physical play/leisure (PPP) is an important therapy goal of children with motor impairments. Evidence for interventions promoting PPP in these children is scarce. The first step is to identify modifiable, clinically meaningful predictors of PPP for targeting by interventions. Objective The study objective was to identify, in children with motor impairments, body function and structure, activity, environmental, and personal factors related to PPP and modifiable by therapists. Design This was a mixed-methods, intervention development study. The World Health Organization framework International Classification of Functioning, Disability and Health was used. Methods Participants were children (6–8 years old) with motor impairments, mobilizing independently with or without equipment and seen by physical therapists or occupational therapists in 6 regions in the United Kingdom, and their parents. Self-reported PPP was assessed with the Children's Assessment of Participation and Enjoyment. Modifiable-factor data were collected with therapists' observations, parent questionnaires, and child-friendly interviews. The Children's Assessment of Participation and Enjoyment, therapist, and parent data were analyzed using descriptive statistics and linear regression. Interview data were analyzed for emerging themes. Results Children's (n=195) PPP (X=18 times per week, interquartile range=11–25) was mainly ‘recreational’ (eg, pretend play, playing with pets) rather than ‘active physical’ (eg, riding a bike/scooter). Parents (n=152) reported positive beliefs about children's PPP but various levels of family PPP. Therapists reported 23 unique impairments (eg, muscle tone), 16 activity limitations (eg, walking), and 3 personal factors (eg, child's PPP confidence). Children interviewed (n=17) reported a strong preference for active play but indicated that adults regulated their PPP. Family PPP and impairment in the child's movement-related body

  14. Participation in Physical Play and Leisure in Children With Motor Impairments: Mixed-Methods Study to Generate Evidence for Developing an Intervention.

    PubMed

    Kolehmainen, Niina; Ramsay, Craig; McKee, Lorna; Missiuna, Cheryl; Owen, Christine; Francis, Jill

    2015-10-01

    Participation in physical play/leisure (PPP) is an important therapy goal of children with motor impairments. Evidence for interventions promoting PPP in these children is scarce. The first step is to identify modifiable, clinically meaningful predictors of PPP for targeting by interventions. The study objective was to identify, in children with motor impairments, body function and structure, activity, environmental, and personal factors related to PPP and modifiable by therapists. This was a mixed-methods, intervention development study. The World Health Organization framework International Classification of Functioning, Disability and Health was used. Participants were children (6-8 years old) with motor impairments, mobilizing independently with or without equipment and seen by physical therapists or occupational therapists in 6 regions in the United Kingdom, and their parents. Self-reported PPP was assessed with the Children's Assessment of Participation and Enjoyment. Modifiable-factor data were collected with therapists' observations, parent questionnaires, and child-friendly interviews. The Children's Assessment of Participation and Enjoyment, therapist, and parent data were analyzed using descriptive statistics and linear regression. Interview data were analyzed for emerging themes. Children's (n=195) PPP (X=18 times per week, interquartile range=11-25) was mainly 'recreational' (eg, pretend play, playing with pets) rather than 'active physical' (eg, riding a bike/scooter). Parents (n=152) reported positive beliefs about children's PPP but various levels of family PPP. Therapists reported 23 unique impairments (eg, muscle tone), 16 activity limitations (eg, walking), and 3 personal factors (eg, child's PPP confidence). Children interviewed (n=17) reported a strong preference for active play but indicated that adults regulated their PPP. Family PPP and impairment in the child's movement-related body structures explained 18% of the variation in PPP. Family

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

    PubMed

    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.

  16. Effects of manufactured nanomaterials on fishes: a target organ and body systems physiology approach.

    PubMed

    Handy, R D; Al-Bairuty, G; Al-Jubory, A; Ramsden, C S; Boyle, D; Shaw, B J; Henry, T B

    2011-10-01

    Manufactured nanomaterials (NM) are already used in consumer products and exposure modelling predicts releases of ng to low µg l(-1) levels of NMs into surface waters. The exposure of aquatic ecosystems, and therefore fishes, to manufactured NMs is inevitable. This review uses a physiological approach to describe the known effects of NMs on the body systems of fishes and to identify the internal target organs, as well as outline aspects of colloid chemistry relevant to fish biology. The acute toxicity data, suggest that the lethal concentration for many NMs is in the mg l(-1) range, and a number of sublethal effects have been reported at concentrations from c. 100 µg to 1 mg l(-1). Exposure to NMs in the water column can cause respiratory toxicity involving altered ventilation, mucus secretion and gill pathology. This may not lead, however, to overt haematological disturbances in the short term. The internal target organs include the liver, spleen and haematopoietic system, kidney, gut and brain; with toxic effects involving oxidative stress, ionoregulatory disturbances and organ pathologies. Some pathology appears to be novel for NMs, such as vascular injury in the brain of rainbow trout Oncorhynchus mykiss with carbon nanotubes. A lack of analytical methods, however, has prevented the reporting of NM concentrations in fish tissues, and the precise uptake mechanisms across the gill or gut are yet to be elucidated. The few dietary exposure studies conducted show no effects on growth or food intake at 10-100 mg kg(-1) inclusions of NMs in the diet of O. mykiss, but there are biochemical disturbances. Early life stages are sensitive to NMs with reports of lethal toxicity and developmental defects. There are many data gaps, however, including how water quality alters physiological responses, effects on immunity and chronic exposure data at environmentally relevant concentrations. Overall, the data so far suggest that the manufactured NMs are not as toxic as some

  17. Pharmacological AMP Kinase Activators Target the Nucleolar Organization and Control Cell Proliferation

    PubMed Central

    Kodiha, Mohamed; Salimi, Ali; Wang, Yi Meng; Stochaj, Ursula

    2014-01-01

    Aims Phenformin, resveratrol and AICAR stimulate the energy sensor 5′-AMP activated kinase (AMPK) and inhibit the first step of ribosome biogenesis, de novo RNA synthesis in nucleoli. Nucleolar activities are relevant to human health, because ribosome production is crucial to the development of diabetic complications. Although the function of nucleoli relies on their organization, the impact of AMPK activators on nucleolar structures is not known. Here, we addressed this question by examining four nucleolar proteins that are essential for ribosome biogenesis. Methods Kidney cells were selected as model system, because diabetic nephropathy is one of the complications associated with diabetes mellitus. To determine the impact of pharmacological agents on nucleoli, we focused on the subcellular and subnuclear distribution of B23/nucleophosmin, fibrillarin, nucleolin and RPA194. This was achieved by quantitative confocal microscopy at the single-cell level in combination with cell fractionation and quantitative Western blotting. Results AMPK activators induced the re-organization of nucleoli, which was accompanied by changes in cell proliferation. Among the compounds tested, phenformin and resveratrol had the most pronounced impact on nucleolar organization. For B23, fibrillarin, nucleolin and RPA194, both agents (i) altered the nucleocytoplasmic distribution and nucleolar association and (ii) reduced significantly the retention in the nucleus. (iii) Phenformin and resveratrol also increased significantly the total concentration of B23 and nucleolin. Conclusions AMPK activators have unique effects on the subcellular localization, nuclear retention and abundance of nucleolar proteins. We propose that the combination of these events inhibits de novo ribosomal RNA synthesis and modulates cell proliferation. Our studies identified nucleolin as a target that is especially sensitive to pharmacological AMPK activators. Because of its response to pharmacological agents

  18. Pharmacological AMP kinase activators target the nucleolar organization and control cell proliferation.

    PubMed

    Kodiha, Mohamed; Salimi, Ali; Wang, Yi Meng; Stochaj, Ursula

    2014-01-01

    Phenformin, resveratrol and AICAR stimulate the energy sensor 5'-AMP activated kinase (AMPK) and inhibit the first step of ribosome biogenesis, de novo RNA synthesis in nucleoli. Nucleolar activities are relevant to human health, because ribosome production is crucial to the development of diabetic complications. Although the function of nucleoli relies on their organization, the impact of AMPK activators on nucleolar structures is not known. Here, we addressed this question by examining four nucleolar proteins that are essential for ribosome biogenesis. Kidney cells were selected as model system, because diabetic nephropathy is one of the complications associated with diabetes mellitus. To determine the impact of pharmacological agents on nucleoli, we focused on the subcellular and subnuclear distribution of B23/nucleophosmin, fibrillarin, nucleolin and RPA194. This was achieved by quantitative confocal microscopy at the single-cell level in combination with cell fractionation and quantitative Western blotting. AMPK activators induced the re-organization of nucleoli, which was accompanied by changes in cell proliferation. Among the compounds tested, phenformin and resveratrol had the most pronounced impact on nucleolar organization. For B23, fibrillarin, nucleolin and RPA194, both agents (i) altered the nucleocytoplasmic distribution and nucleolar association and (ii) reduced significantly the retention in the nucleus. (iii) Phenformin and resveratrol also increased significantly the total concentration of B23 and nucleolin. AMPK activators have unique effects on the subcellular localization, nuclear retention and abundance of nucleolar proteins. We propose that the combination of these events inhibits de novo ribosomal RNA synthesis and modulates cell proliferation. Our studies identified nucleolin as a target that is especially sensitive to pharmacological AMPK activators. Because of its response to pharmacological agents, nucleolin represents a potential

  19. Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID)

    PubMed Central

    Hainsworth, Atticus H; Yeo, Natalie E; Weekman, Erica M; Wilcock, Donna M

    2016-01-01

    Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3–10µM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100–200µM), mild-moderate hyperhomocysteinemia ([HCy]: 10–100µM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100 µM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support Hcy as a mediator for VCID. In our view further trails of combined B-vitamin supplementation are called for, incorporating lessons from previous trails and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; target cohorts with low baseline B-vitamin status. PMID:26689889

  20. KCNQ Channels Regulate Age-Related Memory Impairment

    PubMed Central

    Cavaliere, Sonia; Malik, Bilal R.; Hodge, James J. L.

    2013-01-01

    In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment. PMID:23638087

  1. A new look at the WHOQOL as health-related quality of life instrument among visually impaired people using Rasch analysis.

    PubMed

    Gothwal, Vijaya K; Srinivas, Marmamula; Rao, Gullapalli N

    2013-05-01

    To examine the psychometric characteristics of the World Health Organization quality of life instrument-modified Indian version (modified WHOQOL) and its subscales in adults with visual impairment (VI) using Rasch analysis. Cross-sectional data were of people aged ≥40 years with VI (n = 1,333) who responded to the modified WHOQOL in the Andhra Pradesh Eye Disease Study, India. Rasch analysis was used to explore the instrument and its subscales for key indices such as measurement precision by person separation reliability, PSR (i.e., discrimination between strata of participants' health-related QOL [HRQOL], recommended minimum value 0.8), unidimensionality (i.e., measurement of a single construct), and targeting (i.e., matching of item difficulty to participants' HRQOL). Rasch-guided iterative approach including category re-organization to enable threshold ordering and item deletion to overcome multidimensionality resulted in a unidimensional 9-item WHOQOL and a 6-item level of independence (LOI) subscale with adequate PSR (0.81 and 0.82, respectively). Targeting was sub-optimal for both (-1.58 logits for WHOQOL and -2.55 logits for the subscale). Remaining subscales were dysfunctional. The WHOQOL and LOI subscale can be improved and shortened, and the Rasch-revised versions are likely to assess the HROQL of VI patients best because of their brevity, reliability, and unidimensionality.

  2. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2010 CFR

    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... are still disabled under § 404.1594. [50 FR 50136, Dec. 6, 1985] ...

  3. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 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... are still disabled under § 404.1594. [50 FR 50136, Dec. 6, 1985] ...

  4. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 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... are still disabled under § 404.1594. [50 FR 50136, Dec. 6, 1985] ...

  5. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 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... are still disabled under § 404.1594. [50 FR 50136, Dec. 6, 1985] ...

  6. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 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... are still disabled under § 404.1594. [50 FR 50136, Dec. 6, 1985] ...

  7. Age-related impairment on a forced-choice version of the Mnemonic Similarity Task.

    PubMed

    Huffman, Derek J; Stark, Craig E L

    2017-02-01

    Previous studies from our lab have indicated that healthy older adults are impaired in their ability to mnemonically discriminate between previously viewed objects and similar lure objects in the Mnemonic Similarity Task (MST). These studies have used either old/similar/new or old/new test formats. The forced-choice test format (e.g., "Did you see object A or object A' during the encoding phase?") relies on different assumptions than the old/new test format (e.g., "Did you see this object during the encoding phase?"); hence, converging evidence from these approaches would bolster the conclusion that healthy aging is accompanied by impaired performance on the MST. Consistent with our hypothesis, healthy older adults exhibited impaired performance on a forced-choice test format that required discriminating between a target and a similar lure. We also tested the hypothesis that age-related impairments on the MST could be modeled within a global matching computational framework. We found that decreasing the probability of successful feature encoding in the models caused changes that were similar to the empirical data in healthy older adults. Collectively, our behavioral results using the forced-choice format extend the finding that healthy aging is accompanied by an impaired ability to discriminate between targets and similar lures, and our modeling results suggest that a diminished probability of encoding stimulus features is a candidate mechanism for memory changes in healthy aging. We also discuss the ability of global matching models to account for findings in other studies that have used variants on mnemonic similarity tasks. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets

    PubMed Central

    Dong, Li; Zhong, Xiang; Ahmad, Hussain; Li, Wei; Wang, Yuanxiao; Zhang, Lili

    2014-01-01

    Intrauterine growth restriction (IUGR) is a very common problem in both piglet and human neonate populations. We hypothesized that IUGR neonates have impaired intestinal mucosal immunity from birth. Using neonatal piglets as IUGR models, immune organ weights, the weight and length of the small intestine (SI), intestinal morphology, intraepithelial immune cell numbers, levels of cytokines and immunoglobulins, and the relative gene expression of cytokines in the SI were investigated. IUGR neonatal piglets were observed to have lower absolute immune organ weight and SI length, decreased relative weights of the thymus, spleen, mesenteric lymph node, and thinner but longer SIs. Damaged and jagged villi, shorter microvilli, presence of autophagosomes, swelled mitochondria, and decreased villus surface areas were also found in the SIs of IUGR neonatal piglets. We also found a smaller number of epithelial goblet cells and lymphocytes in the SIs of IUGR neonates. In addition, we detected reduced levels of the cytokines TNF-α and IFN-γ and decreased gene expression of cytokines in IUGR neonates. In conclusion, IUGR was shown to impair the mucosal immunity of the SI in neonatal piglets, and the ileum was the major site of impairment. PMID:24710659

  9. Impaired immune function in seals and laboratory rats exposed to dioxin-like compounds from Baltic herring

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ross, P.S.; Swart, R.L. de; Timmerman, H.H.

    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 lymphoidmore » 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.« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Merk, Hans F.; Baron, Jens M.; Neis, Mark M.

    2007-11-01

    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 majormore » 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.« less

  11. Impaired theta-gamma coupling during working memory performance in schizophrenia.

    PubMed

    Barr, Mera S; Rajji, Tarek K; Zomorrodi, Reza; Radhu, Natasha; George, Tony P; Blumberger, Daniel M; Daskalakis, Zafiris J

    2017-11-01

    Working memory deficits represent a core feature of schizophrenia. These deficits have been associated with dysfunctional dorsolateral prefrontal cortex (DLPFC) cortical oscillations. Theta-gamma coupling describes the modulation of gamma oscillations by theta phasic activity that has been directly associated with the ordering of information during working memory performance. Evaluating theta-gamma coupling may provide greater insight into the neural mechanisms mediating working memory deficits in this disorder. Thirty-eight patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls performed the verbal N-Back task administered at 4 levels, while EEG was recorded. Theta (4-7Hz)-gamma (30-50Hz) coupling was calculated for target and non-target correct trials for each working memory load. The relationship between theta-gamma coupling and accuracy was determined. Theta-gamma coupling was significantly and selectively impaired during correct responses to target letters among schizophrenia patients compared to healthy controls. A significant and positive relationship was found between theta-gamma coupling and 3-Back accuracy in controls, while this relationship was not observed in patients. These findings suggest that impaired theta-gamma coupling contribute to working memory dysfunction in schizophrenia. Future work is needed to evaluate the predictive utility of theta-gamma coupling as a neurophysiological marker for functional outcomes in this disorder. Copyright © 2017. Published by Elsevier B.V.

  12. Age-dependent impairment of auditory processing under spatially focused and divided attention: an electrophysiological study.

    PubMed

    Wild-Wall, Nele; Falkenstein, Michael

    2010-01-01

    By using event-related potentials (ERPs) the present study examines if age-related differences in preparation and processing especially emerge during divided attention. Binaurally presented auditory cues called for focused (valid and invalid) or divided attention to one or both ears. Responses were required to subsequent monaurally presented valid targets (vowels), but had to be suppressed to non-target vowels or invalidly cued vowels. Middle-aged participants were more impaired under divided attention than young ones, likely due to an age-related decline in preparatory attention following cues as was reflected in a decreased CNV. Under divided attention, target processing was increased in the middle-aged, likely reflecting compensatory effort to fulfill task requirements in the difficult condition. Additionally, middle-aged participants processed invalidly cued stimuli more intensely as was reflected by stimulus ERPs. The results suggest an age-related impairment in attentional preparation after auditory cues especially under divided attention and latent difficulties to suppress irrelevant information.

  13. TRACE GAS CONCENTRATIONS IN STREAMS - EARLY WARNING INDICATORS OF STREAM IMPAIRMENT?

    EPA Science Inventory

    Surface water contamination and resultant impairment of aquatic ecosystem functioning are serious environmental problems, caused in large part by land use changes and excess organic waste inputs associated with agriculture and residential and industrial development. Headwater st...

  14. Impaired threat prioritisation after selective bilateral amygdala lesions

    PubMed Central

    Bach, Dominik R.; Hurlemann, Rene; Dolan, Raymond J.

    2015-01-01

    The amygdala is proposed to process threat-related information in non-human animals. In humans, empirical evidence from lesion studies has provided the strongest evidence for a role in emotional face recognition and social judgement. Here we use a face-in-the-crowd (FITC) task which in healthy control individuals reveals prioritised threat processing, evident in faster serial search for angry compared to happy target faces. We investigate AM and BG, two individuals with bilateral amygdala lesions due to Urbach–Wiethe syndrome, and 16 control individuals. In lesion patients we show a reversal of a threat detection advantage indicating a profound impairment in prioritising threat information. This is the first direct demonstration that human amygdala lesions impair prioritisation of threatening faces, providing evidence that this structure has a causal role in responding to imminent danger. PMID:25282058

  15. Effects of clonidine and scopolamine on multiple target detection in rapid serial visual presentation.

    PubMed

    Brown, Stephen B R E; Slagter, Heleen A; van Noorden, Martijn S; Giltay, Erik J; van der Wee, Nic J A; Nieuwenhuis, Sander

    2016-01-01

    The specific role of neuromodulator systems in regulating rapid fluctuations of attention is still poorly understood. In this study, we examined the effects of clonidine and scopolamine on multiple target detection in a rapid serial visual presentation task to assess the role of the central noradrenergic and cholinergic systems in temporal attention. Eighteen healthy volunteers took part in a crossover double-dummy study in which they received clonidine (150/175 μg), scopolamine (1.2 mg), and placebo by mouth in counterbalanced order. A dual-target attentional blink task was administered at 120 min after scopolamine intake and 180 min after clonidine intake. The electroencephalogram was measured during task performance. Clonidine and scopolamine both impaired detection of the first target (T1). For clonidine, this impairment was accompanied by decreased amplitudes of the P2 and P3 components of the event-related potential. The drugs did not impair second-target (T2) detection, except if T2 was presented immediately after T1. The attentional blink for T2 was not affected, in line with a previous study that found no effect of clonidine on the attentional blink. These and other results suggest that clonidine and scopolamine may impair temporal attention through a decrease in tonic alertness and that this decrease in alertness can be temporarily compensated by a phasic alerting response to a salient stimulus. The comparable behavioral effects of clonidine and scopolamine are consistent with animal studies indicating close interactions between the noradrenergic and cholinergic neuromodulator systems.

  16. Hispanic organ donation: impact of a Spanish-language organ donation campaign.

    PubMed Central

    Alvaro, Eusebio M.; Jones, Sara Pace; Robles, Antonio Santa Maria; Siegel, Jason

    2006-01-01

    OBJECTIVES: Hispanic Americans have a substantial need for organ transplants and are underrepresented among organ donors, yet very little is known about how to increase available donors in this community. This study assesses the impact of a Spanish-language media campaign targeting organ donation among Hispanic Americans in two urban Arizona counties. METHODS: The study collected data via four surveys conducted before and after implementation of a Spanish-language media campaign targeting organ donation among Spanish-dominant Hispanic Americans in Pima and Maricopa counties in Arizona. The main intervention consisted of four Spanish-language television advertisements and two Spanish-language radio advertisements. RESULTS: The media campaign was successfully implemented and attained substantial exposure among the target audience. Postintervention beliefs were more prodonation, and there was more family discussion postintervention. In both counties, residents exposed to the campaign reported more prodonation beliefs and family discussion. Exposed Maricopa residents were also more likely to be potential donors. CONCLUSIONS: Study data indicate a positive impact of a media campaign targeting organ donation beliefs and behaviors among Spanish-dominant Hispanic Americans in Arizona. It is hoped that these findings will stimulate further research in this important area. PMID:16532975

  17. Peripheral surgical wounding may induce cognitive impairment through interlukin-6-dependent mechanisms in aged mice.

    PubMed

    Dong, Yuanlin; Xu, Zhipeng; Huang, Lining; Zhang, Yiying; Xie, Zhongcong

    2016-01-01

    Post-operative cognitive dysfunction (POCD) is associated with morbidity, mortality and increased cost of medical care. However, the neuropathogenesis and targeted interventions of POCD remain largely to be determined. We have found that the peripheral surgical wounding induces an age-dependent Aβ accumulation, neuroinflammation and cognitive impairment in aged mice. Pro-inflammatory cytokine interlukin-6 (IL-6) has been reported to be associated with cognitive impairment in rodents and humans. However, the role of IL-6 in the neuropathogenesis of POCD is unknown. We therefore employed pharmacological (IL-6 antibody) and genetic (knockout of IL-6) approach to investigate whether IL-6 contributed to the peripheral surgical wounding-induced cognitive impairment in aged mice. Abdominal surgery under local anesthesia (peripheral surgical wounding) was established in 18-month-old wild-type and IL-6 knockout mice ( n = 6 to 10 in each group). Brain level of IL-6 and cognitive function in the mice were determined by western blot, ELISA at the end of procedure, and Fear Conditioning System at 7 days after the procedure. The peripheral surgical wounding increased the level of IL-6 in the hippocampus of aged wild-type, but not IL-6 knockout mice. IL-6 antibody ameliorated the peripheral surgical wounding-induced cognitive impairment in the aged wild-type mice. Finally, the peripheral surgical wounding did not induce cognitive impairment in the aged IL-6 knockout mice. These data suggested that IL-6 would be a required pro-inflammatory cytokine for the peripheral surgical wounding-induced cognitive impairment. Given this, further studies are warranted to investigate the role of IL-6 in the neuropathogenesis and targeted interventions of POCD.

  18. Peripheral surgical wounding may induce cognitive impairment through interlukin-6-dependent mechanisms in aged mice

    PubMed Central

    Dong, Yuanlin; Xu, Zhipeng; Huang, Lining; Zhang, Yiying; Xie, Zhongcong

    2016-01-01

    Post-operative cognitive dysfunction (POCD) is associated with morbidity, mortality and increased cost of medical care. However, the neuropathogenesis and targeted interventions of POCD remain largely to be determined. We have found that the peripheral surgical wounding induces an age-dependent Aβ accumulation, neuroinflammation and cognitive impairment in aged mice. Pro-inflammatory cytokine interlukin-6 (IL-6) has been reported to be associated with cognitive impairment in rodents and humans. However, the role of IL-6 in the neuropathogenesis of POCD is unknown. We therefore employed pharmacological (IL-6 antibody) and genetic (knockout of IL-6) approach to investigate whether IL-6 contributed to the peripheral surgical wounding-induced cognitive impairment in aged mice. Abdominal surgery under local anesthesia (peripheral surgical wounding) was established in 18-month-old wild-type and IL-6 knockout mice (n = 6 to 10 in each group). Brain level of IL-6 and cognitive function in the mice were determined by western blot, ELISA at the end of procedure, and Fear Conditioning System at 7 days after the procedure. The peripheral surgical wounding increased the level of IL-6 in the hippocampus of aged wild-type, but not IL-6 knockout mice. IL-6 antibody ameliorated the peripheral surgical wounding-induced cognitive impairment in the aged wild-type mice. Finally, the peripheral surgical wounding did not induce cognitive impairment in the aged IL-6 knockout mice. These data suggested that IL-6 would be a required pro-inflammatory cytokine for the peripheral surgical wounding-induced cognitive impairment. Given this, further studies are warranted to investigate the role of IL-6 in the neuropathogenesis and targeted interventions of POCD. PMID:28217289

  19. Meeting the Needs of Students with Coexisting Visual Impairments and Learning Disabilities

    ERIC Educational Resources Information Center

    Jones, Beth A.; Hensley-Maloney, Lauren

    2015-01-01

    The coexistence of visual impairments and learning disabilities presents unique challenges. It is imperative that teachers be apprised of the characteristics of this population as well as instructional strategies targeted at meeting their unique needs. The authors highlight typical patterns of performance and provide suggestions for effective…

  20. Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

    PubMed

    Lopes, M H; Santos, T G; Rodrigues, B R; Queiroz-Hazarbassanov, N; Cunha, I W; Wasilewska-Sampaio, A P; Costa-Silva, B; Marchi, F A; Bleggi-Torres, L F; Sanematsu, P I; Suzuki, S H; Oba-Shinjo, S M; Marie, S K N; Toulmin, E; Hill, A F; Martins, V R

    2015-06-01

    Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.

  1. Smart-system of distance learning of visually impaired people based on approaches of artificial intelligence

    NASA Astrophysics Data System (ADS)

    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.

  2. Impaired limb reaction to displacement of center of gravity in rats with unilateral striatal ischemic injury.

    PubMed

    Nobile, Cameron W; Palmateer, Julie M; Kane, Jackie; Hurn, Patricia D; Schallert, Timothy; Adkins, DeAnna L

    2014-10-01

    Clinical stroke often results in impaired balance and increased vulnerability to severe injuries due to falling. To evaluate potential preclinical treatments that might target these deficits, it will be important to include tests capable of assessing these impairments chronically in animal models. Previously, we developed a postural instability test (PIT) that revealed chronic, unilateral impairments in postural stability in rat models of hemi-Parkinson's disease (PD) and of unilateral cervical spinal cord injury. Here, we investigated whether this test was also capable of revealing long-term stroke-induced impairments in postural support in rats. Additionally, we examined the ability of more common tests of sensorimotor function to detect chronic impairments. We found that the PIT detected chronic deficits in postural stability/balance enduring for up to 6 weeks post-stroke, outlasting impairments detected in other tests of forelimb sensorimotor function, including asymmetries in upright postural support (cylinder test) and vibrissae-evoked forelimb placing.

  3. Structural quality indicators to support quality of care for older people with cognitive impairment in emergency departments.

    PubMed

    Schnitker, Linda M; Martin-Khan, Melinda; Burkett, Ellen; Brand, Caroline A; Beattie, Elizabeth R A; Jones, Richard N; Gray, Len C

    2015-03-01

    The purpose of this study was to identify the structural quality of care domains and to establish a set of structural quality indicators (SQIs) for the assessment of care of older people with cognitive impairment in emergency departments (EDs). A structured approach to SQI development was undertaken including: 1) a comprehensive search of peer-reviewed and gray literature focusing on identification of evidence-based interventions targeting structure of care of older patients with cognitive impairment and existing SQIs; 2) a consultative process engaging experts in the care of older people and epidemiologic methods (i.e., advisory panel) leading to development of a draft set of SQIs; 3) field testing of drafted SQIs in eight EDs, leading to refinement of the SQI set; and 4) an independent voting process among the panelists for SQI inclusion in a final set, using preestablished inclusion and exclusion criteria. At the conclusion of the process, five SQIs targeting the management of older ED patients with cognitive impairment were developed: 1) the ED has a policy outlining the management of older people with cognitive impairment during the ED episode of care; 2) the ED has a policy outlining issues relevant to carers of older people with cognitive impairment, encompassing the need to include the (family) carer in the ED episode of care; 3) the ED has a policy outlining the assessment and management of behavioral symptoms, with specific reference to older people with cognitive impairment; 4) the ED has a policy outlining delirium prevention strategies, including the assessment of patients' delirium risk factors; and 5) the ED has a policy outlining pain assessment and management for older people with cognitive impairment. This article presents a set of SQIs for the evaluation of performance in caring for older people with cognitive impairment in EDs. © 2015 by the Society for Academic Emergency Medicine.

  4. Mild Cognitive Impairment

    MedlinePlus

    ... your local chapter Join our online community Mild Cognitive Impairment Mild cognitive impairment (MCI) causes a slight ... About Symptoms Diagnosis Causes & risks Treatments About Mild Cognitive Impairment Prevalence of MCI Approximately 15 to 20 ...

  5. Reaching to multiple targets when standing: the spatial organization of feedforward postural adjustments.

    PubMed

    Leonard, Julia A; Brown, Ryan H; Stapley, Paul J

    2009-04-01

    We examined the spatial organization of feedforward postural adjustments produced prior to and during voluntary arm reaching movements executed while standing. We sought to investigate whether the activity of postural muscles before and during reaching was directionally tuned and whether a strategy of horizontal force constraint could be observed. To this end, eight human subjects executed self-paced reach-to-point movements on the random illumination of one of 13 light targets placed within a 180 degrees array centered along the midline of the body. Analysis was divided into two periods: a first corresponding to the 250 ms preceding the onset of the reaching movements (termed pPA period) and a second 250-ms period immediately preceding target attainment (the aPA period). For both periods, electromyographic activity of the lower limb muscles revealed a clear directional tuning, with groups of muscles being activated for similar directions of reach. Analysis of horizontal ground reaction forces supported the existence of a force constraint strategy only for the pPA period, however, with those in the aPA period being more widely dispersed. We suggest that the strategy adopted for feedforward pPAs is one where the tuned muscle synergies constrain the forces diagonally away from the center of mass (CoM) to move it within the support base. However, the need to control for final finger and body position for each target during the aPA phase resulted in a distribution of vectors across reaching directions. Overall, our results would support the idea that endpoint limb force during postural tasks depends on the use of functional muscle synergies, which are used to displace the CoM or decelerate the body at the end of the reach.

  6. Erectile dysfunction and target organ damage in the early stages of hypertension.

    PubMed

    Kakkavas, Apostolos; Tsioufis, Costas; Tsiachris, Dimitris; Thomopoulos, Costas; Dimitriadis, Kyriakos; Milkas, Anastasios; Alexopoulos, Dimitrios; Kallikazaros, Ioannis; Stefanadis, Christodoulos

    2013-09-01

    The authors investigated whether erectile dysfunction (ED) in the early stages of hypertension is associated with heightened end-organ damage. A total of 174 consecutive men with untreated, newly diagnosed essential hypertension (aged 50.3 years, office blood pressure [BP] 150/98 mm Hg) were studied. All participants underwent 24-hour ambulatory BP monitoring, blood examination, albumin-creatinine ratio, carotid-femoral pulse-wave velocity assessment, and echocardiography for estimation of left ventricular mass index and diastolic function. Hypertensive men with ED (n=43, 24.7%) compared with those without ED were older (by 6.4 years, P<.05), had greater 24-hour pulse pressure (by 4.3 mm Hg, P=.011) and a greater prevalence of nondipping status (72.2% vs 46.7%, P=.008), while the two groups did not differ in plasma glucose, lipid, creatinine, and albumin/creatinine ratio levels. Regarding cardiac adaptations, hypertensive men with ED exhibited only significantly lower tissue Doppler imaging-derived Em (by 1.6 cm/s, adjusted P=.035), while no difference in left ventricular mass index or pulse wave velocity were detected. ED in the setting of untreated newly diagnosed essential hypertension does not have an unfavorable impact on traditional markers of target organ damage. This finding suggests that ED assessment might not refine the traditional risk stratification procedure at least in the early stages of hypertensive disease. ©2013 Wiley Periodicals, Inc.

  7. The Classroom Notetaker: How To Organize a Program Serving Students with Hearing Impairments.

    ERIC Educational Resources Information Center

    Wilson, Jimmie Joan

    This guide describes how to establish a notetaking program to benefit students with hearing impairments in mainstream settings. Chapter 1 discusses the need for notetakers and includes subjects such as providing equal access, high-tech and low-tech notetaking, how the notes can be used, and who can use the notes. Chapter 2 provides information on…

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

    PubMed

    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.

  9. Emotion recognition in mild cognitive impairment: relationship to psychosocial disability and caregiver burden.

    PubMed

    McCade, Donna; Savage, Greg; Guastella, Adam; Hickie, Ian B; Lewis, Simon J G; Naismith, Sharon L

    2013-09-01

    Impaired emotion recognition in dementia is associated with increased patient agitation, behavior management difficulties, and caregiver burden. Emerging evidence supports the presence of very early emotion recognition difficulties in mild cognitive impairment (MCI); however, the relationship between these impairments and psychosocial measures is not yet explored. Emotion recognition abilities of 27 patients with nonamnestic MCI (naMCI), 29 patients with amnestic MCI (aMCI), and 22 control participants were assessed. Self-report measures assessed patient functional disability, while informants rated the degree of burden they experienced. Difficulties in recognizing anger was evident in the amnestic subtype. Although both the patient groups reported greater social functioning disability, compared with the controls, a relationship between social dysfunction and anger recognition was evident only for patients with naMCI. A significant association was found between burden and anger recognition in patients with aMCI. Impaired emotion recognition abilities impact MCI subtypes differentially. Interventions targeted at patients with MCI, and caregivers are warranted.

  10. Should we add visual acuity ratios to referral criteria for potential cerebral visual impairment?

    PubMed

    van der Zee, Ymie J; Stiers, Peter; Evenhuis, Heleen M

    To determine whether the assessment of visual acuity ratios might improve the referral of children with (sub)normal visual acuity but at risk of cerebral visual impairment. In an exploratory study, we assessed visual acuity, crowding ratio and the ratios between grating acuity (Teller Acuity Cards-II) and optotype acuity (Cambridge Crowding Cards) in 60 typically developing school children (mean age 5y8m±1y1m), 21 children with ocular abnormalities only (5y7m±1y9m) and 26 children with (suspected) brain damage (5y7m±1y11m). Sensitivities and specificities were calculated for targets and controls from the perspective of different groups of diagnosticians: youth health care professionals (target: children with any visual abnormalities), ophthalmologists and low vision experts (target: children at risk of cerebral visual impairment). For youth health care professionals subnormal visual acuity had the best sensitivity (76%) and specificity (70%). For ophthalmologists and low vision experts the crowding ratio had the best sensitivity (67%) and specificity (79 and 86%). Youth health care professionals best continue applying subnormal visual acuity for screening, whereas ophthalmologists and low vision experts best add the crowding ratio to their routine diagnostics, to distinguish children at risk of visual impairment in the context of brain damage from children with ocular pathology only. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  11. ALCOHOL AND DISTRACTION INTERACT TO IMPAIR DRIVING PERFORMANCE

    PubMed Central

    Harrison, Emily L. R.; Fillmore, Mark T.

    2011-01-01

    Background Recognition of the risks associated with alcohol intoxication and driver distraction has led to a wealth of simulated driving research aimed at studying the adverse effects of each of these factors. Research on driving has moved beyond the individual, separate examination of these factors to the examination of potential interactions between alcohol intoxication and driver distraction. In many driving situations, distractions are commonplace and might have little or no disruptive influence on primary driving functions. Yet, such distractions might become disruptive to a driver who is intoxicated. Methods The present study examined the interactive impairing effects of alcohol intoxication and driver distraction on simulated driving performance in 40 young adult drivers using a divided attention task as a distracter activity. The interactive influence of alcohol and distraction was tested by having drivers perform the driving task under four different conditions: 0.65 g/kg alcohol; 0.65 g/kg alcohol + divided attention; placebo; and placebo + divided attention. Results As hypothesized, divided attention had no impairing effect on driving performance in sober drivers. However, under alcohol, divided attention exacerbated the impairing effects of alcohol on driving precision. Conclusions Alcohol and distraction continue to be appropriate targets for research into ways to reduce the rates of driving-related fatalities and injuries. Greater consideration of how alcohol and distraction interact to impair aspects of driving performance can further efforts to create prevention and intervention measures to protect drivers, particularly young adults. PMID:21277119

  12. Alcohol and distraction interact to impair driving performance.

    PubMed

    Harrison, Emily L R; Fillmore, Mark T

    2011-08-01

    Recognition of the risks associated with alcohol intoxication and driver distraction has led to a wealth of simulated driving research aimed at studying the adverse effects of each of these factors. Research on driving has moved beyond the individual, separate examination of these factors to the examination of potential interactions between alcohol intoxication and driver distraction. In many driving situations, distractions are commonplace and might have little or no disruptive influence on primary driving functions. Yet, such distractions might become disruptive to a driver who is intoxicated. The present study examined the interactive impairing effects of alcohol intoxication and driver distraction on simulated driving performance in 40 young adult drivers using a divided attention task as a distracter activity. The interactive influence of alcohol and distraction was tested by having drivers perform the driving task under four different conditions: 0.65 g/kg alcohol; 0.65 g/kg alcohol+divided attention; placebo; and placebo+divided attention. As hypothesized, divided attention had no impairing effect on driving performance in sober drivers. However, under alcohol, divided attention exacerbated the impairing effects of alcohol on driving precision. Alcohol and distraction continue to be appropriate targets for research into ways to reduce the rates of driving-related fatalities and injuries. Greater consideration of how alcohol and distraction interact to impair aspects of driving performance can further efforts to create prevention and intervention measures to protect drivers, particularly young adults. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling.

    PubMed

    Liston, Adrian; Hardy, Kristine; Pittelkow, Yvonne; Wilson, Susan R; Makaroff, Lydia E; Fahrer, Aude M; Goodnow, Christopher C

    2007-01-01

    T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death.

  14. Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling

    PubMed Central

    Liston, Adrian; Hardy, Kristine; Pittelkow, Yvonne; Wilson, Susan R; Makaroff, Lydia E; Fahrer, Aude M; Goodnow, Christopher C

    2007-01-01

    Background T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain Results Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. Conclusion The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death. PMID:17239257

  15. Targeted Treatments in Autism and Fragile X Syndrome

    ERIC Educational Resources Information Center

    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…

  16. Causes of blindness and visual impairment in Pakistan. The Pakistan national blindness and visual impairment survey

    PubMed Central

    Dineen, B; Bourne, R R A; Jadoon, Z; Shah, S P; Khan, M A; Foster, A; Gilbert, C E; Khan, M D

    2007-01-01

    Objective To determine the causes of blindness and visual impairment in adults (⩾30 years old) in Pakistan, and to explore socio‐demographic variations in cause. Methods A multi‐stage, stratified, cluster random sampling survey was used to select a nationally representative sample of adults. Each subject was interviewed, had their visual acuity measured and underwent autorefraction and fundus/optic disc examination. Those with a visual acuity of <6/12 in either eye underwent a more detailed ophthalmic examination. Causes of visual impairment were classified according to the accepted World Health Organization (WHO) methodology. An exploration of demographic variables was conducted using regression modeling. Results A sample of 16 507 adults (95.5% of those enumerated) was examined. Cataract was the most common cause of blindness (51.5%; defined as <3/60 in the better eye on presentation) followed by corneal opacity (11.8%), uncorrected aphakia (8.6%) and glaucoma (7.1%). Posterior capsular opacification accounted for 3.6% of blindness. Among the moderately visually impaired (<6/18 to ⩾6/60), refractive error was the most common cause (43%), followed by cataract (42%). Refractive error as a cause of severe visual impairment/blindness was significantly higher in rural dwellers than in urban dwellers (odds ratio (OR) 3.5, 95% CI 1.1 to 11.7). Significant provincial differences were also identified. Overall we estimate that 85.5% of causes were avoidable and that 904 000 adults in Pakistan have cataract (<6/60) requiring surgical intervention. Conclusions This comprehensive survey provides reliable estimates of the causes of blindness and visual impairment in Pakistan. Despite expanded surgical services, cataract still accounts for over half of the cases of blindness in Pakistan. One in eight blind adults has visual loss from sequelae of cataract surgery. Services for refractive errors need to be further expanded and integrated into eye care services

  17. Endothelial progenitor cells dysfunction and impaired tissue reparation: The missed link in diabetes mellitus development.

    PubMed

    Berezin, Alexander E

    Diabetes mellitus (DM) is considered a leading cause of premature cardiovascular (CV) mortality and morbidity in general population and in individuals with known CV disease. Recent animal and clinical studies have shown that reduced number and weak function of endothelial progenitor cells (EPCs) may not only indicate to higher CV risk, but contribute to the impaired heart and vessels reparation in patients with DM. Moreover, EPCs having a protective impact on the vasculature may mediate the functioning of other organs and systems. Therefore, EPCs dysfunction is probably promising target for DM treatment strategy, while the role of restoring of EPCs number and functionality in CV risk diminish and reduce of DM-related complications is not fully clear. The aim of the review is summary of knowledge regarding EPCs dysfunction in DM patients. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  18. MicroRNA-Mediated Rescue of Fear Extinction Memory by miR-144-3p in Extinction-Impaired Mice.

    PubMed

    Murphy, Conor P; Li, Xiang; Maurer, Verena; Oberhauser, Michael; Gstir, Ronald; Wearick-Silva, Luis Eduardo; Viola, Thiago Wendt; Schafferer, Simon; Grassi-Oliveira, Rodrigo; Whittle, Nigel; Hüttenhofer, Alexander; Bredy, Timothy W; Singewald, Nicolas

    2017-06-15

    MicroRNA (miRNA)-mediated control of gene expression suggests that miRNAs are interesting targets and/or biomarkers in the treatment of anxiety- and trauma-related disorders, where often memory-associated gene expression is adversely affected. The role of miRNAs in the rescue of impaired fear extinction was assessed using the 129S1/SvlmJ (S1) mouse model of impaired fear extinction. miRNA microarray analysis, reverse transcription polymerase chain reaction, fluorescent in situ hybridization, lentiviral overexpression, and Luciferase reporter assays were used to gain insight into the mechanisms underlying miRNA-mediated normalization of deficient fear extinction. Rescuing impaired fear extinction via dietary zinc restriction was associated with differential expression of miRNAs in the amygdala. One candidate, miR-144-3p, robustly expressed in the basolateral amygdala, showed specific extinction-induced, but not fear-induced, increased expression in both extinction-rescued S1 mice and extinction-intact C57BL/6 (BL6) mice. miR-144-3p upregulation and effects on subsequent behavioral adaption was assessed in S1 and BL6 mice. miR-144-3p overexpression in the basolateral amygdala rescued impaired fear extinction in S1 mice, led to enhanced fear extinction acquisition in BL6 mice, and furthermore protected against fear renewal in BL6 mice. miR-144-3p targets a number of genes implicated in the control of plasticity-associated signaling cascades, including Pten, Spred1, and Notch1. In functional interaction studies, we revealed that the miR-144-3p target, PTEN, colocalized with miR-144-3p in the basolateral amygdala and showed functional downregulation following successful fear extinction in S1 mice. These findings identify a fundamental role of miR-144-3p in the rescue of impaired fear extinction and suggest this miRNA as a viable target in developing novel treatments for posttraumatic stress disorder and related disorders. Copyright © 2017 Society of Biological

  19. Making sense of mild cognitive impairment: a qualitative exploration of the patient's experience.

    PubMed

    Lingler, Jennifer Hagerty; Nightingale, Marcie C; Erlen, Judith A; Kane, April L; Reynolds, Charles F; Schulz, Richard; DeKosky, Steven T

    2006-12-01

    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 diagnosis. We recruited 12 older adults with amnestic or nonamnestic mild cognitive impairment from a university-based memory disorders clinic. We conducted in-home, semistructured interviews in order to elicit rich descriptions of the personal experience of having mild cognitive impairment. We used the qualitative method of grounded theory to analyze narrative data. Understanding and coming to terms with the syndrome, or assigning meaning, constituted a fundamental aspect of living with a diagnosis of mild cognitive impairment. This process comprised interrelated emotional and cognitive dimensions. Participants employed a range of positive, neutral, and negative phrasing in order to depict their emotional reactions to receiving a diagnosis. Cognitive representations of mild cognitive impairment included both prognosis-focused and face-value appraisals. Expectations of normal aging, personal experience with dementia, and concurrent health problems were key contextual factors that provided the backdrop against which participants assigned meaning to a diagnosis of mild cognitive impairment. Clinicians who disclose diagnoses of mild cognitive impairment need to be mindful of the potential for varying interpretations of the information that is conveyed. Future research needs to include systematic, longitudinal investigations of illness representation and its impact on health behaviors among individuals with mild cognitive impairment.

  20. Separation of cognitive impairments in attention-deficit/hyperactivity disorder into 2 familial factors.

    PubMed

    Kuntsi, Jonna; Wood, Alexis C; Rijsdijk, Frühling; Johnson, Katherine A; Andreou, Penelope; Albrecht, Björn; Arias-Vasquez, Alejandro; Buitelaar, Jan K; McLoughlin, Gráinne; Rommelse, Nanda N J; Sergeant, Joseph A; Sonuga-Barke, Edmund J; Uebel, Henrik; van der Meere, Jaap J; Banaschewski, Tobias; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V; Asherson, Philip

    2010-11-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. An ADHD and control sibling-pair design. Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform

  1. Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome.

    PubMed

    Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Belzberg, H; Wedel, S; Placko, R

    1985-09-01

    The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.

  2. Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model.

    PubMed

    Sharma, Anjali; Porterfield, Joshua E; Smith, Elizabeth; Sharma, Rishi; Kannan, Sujatha; Kannan, Rangaramanujam M

    2018-06-05

    Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer

  3. Multiple Learning Strategies Project. Medical Assistant. Visually Impaired. [Vol. 1.

    ERIC Educational Resources Information Center

    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,…

  4. Perception of Filtered Speech by Children with Developmental Dyslexia and Children with Specific Language Impairments

    PubMed Central

    Goswami, Usha; Cumming, Ruth; Chait, Maria; Huss, Martina; Mead, Natasha; Wilson, Angela M.; Barnes, Lisa; Fosker, Tim

    2016-01-01

    Here we use two filtered speech tasks to investigate children’s processing of slow (<4 Hz) versus faster (∼33 Hz) temporal modulations in speech. We compare groups of children with either developmental dyslexia (Experiment 1) or speech and language impairments (SLIs, Experiment 2) to groups of typically-developing (TD) children age-matched to each disorder group. Ten nursery rhymes were filtered so that their modulation frequencies were either low-pass filtered (<4 Hz) or band-pass filtered (22 – 40 Hz). Recognition of the filtered nursery rhymes was tested in a picture recognition multiple choice paradigm. Children with dyslexia aged 10 years showed equivalent recognition overall to TD controls for both the low-pass and band-pass filtered stimuli, but showed significantly impaired acoustic learning during the experiment from low-pass filtered targets. Children with oral SLIs aged 9 years showed significantly poorer recognition of band pass filtered targets compared to their TD controls, and showed comparable acoustic learning effects to TD children during the experiment. The SLI samples were also divided into children with and without phonological difficulties. The children with both SLI and phonological difficulties were impaired in recognizing both kinds of filtered speech. These data are suggestive of impaired temporal sampling of the speech signal at different modulation rates by children with different kinds of developmental language disorder. Both SLI and dyslexic samples showed impaired discrimination of amplitude rise times. Implications of these findings for a temporal sampling framework for understanding developmental language disorders are discussed. PMID:27303348

  5. Impaired cognition and decision-making in bipolar depression but no 'affective bias' evident.

    PubMed

    Rubinsztein, J S; Michael, A; Underwood, B R; Tempest, M; Sahakian, B J

    2006-05-01

    Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression. We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task). Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for 'sad' targets was not evident on the affective go/no-go task. We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments.

  6. Drug target identification in protozoan parasites.

    PubMed

    Müller, Joachim; Hemphill, Andrew

    2016-08-01

    Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

  7. Drug target identification in protozoan parasites

    PubMed Central

    Müller, Joachim; Hemphill, Andrew

    2016-01-01

    Introduction Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Areas covered Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Expert opinion Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses. PMID:27238605

  8. Accessible GPS: Reorientation and Target Location among Users with Visual Impairments

    ERIC Educational Resources Information Center

    Ponchillia, Paul E.; Rak, Eniko C.; Freeland, Amy L.; LaGrow, Steven J.

    2007-01-01

    This article presents the results of two single-subject experiments that were designed to determine consumers' ability to use a BrailleNote GPS. The participants decreased their mean orientation time from 6 minutes to 45 seconds and increased their target-location efficiency fourfold with BGPS than without BGPS. Additional results and implications…

  9. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

    PubMed

    Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael; Moriarty, Tara J

    2016-01-01

    Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

  10. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false If you become disabled by another impairment... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment...

  11. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false If you become disabled by another impairment... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment...

  12. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false If you become disabled by another impairment... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment...

  13. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false If you become disabled by another impairment... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment...

  14. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment...

  15. A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes.

    PubMed

    Xue, Shuai; Yin, Jianli; Shao, Jiawei; Yu, Yuanhuan; Yang, Linfeng; Wang, Yidan; Xie, Mingqi; Fussenegger, Martin; Ye, Haifeng

    2017-02-01

    Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  16. Bioinformatics and Microarray Analysis of miRNAs in Aged Female Mice Model Implied New Molecular Mechanisms for Impaired Fracture Healing

    PubMed Central

    He, Bing; Zhang, Zong-Kang; Liu, Jin; He, Yi-Xin; Tang, Tao; Li, Jie; Guo, Bao-Sheng; Lu, Ai-Ping; Zhang, Bao-Ting; Zhang, Ge

    2016-01-01

    Impaired fracture healing in aged females is still a challenge in clinics. MicroRNAs (miRNAs) play important roles in fracture healing. This study aims to identify the miRNAs that potentially contribute to the impaired fracture healing in aged females. Transverse femoral shaft fractures were created in adult and aged female mice. At post-fracture 0-, 2- and 4-week, the fracture sites were scanned by micro computed tomography to confirm that the fracture healing was impaired in aged female mice and the fracture calluses were collected for miRNA microarray analysis. A total of 53 significantly differentially expressed miRNAs and 5438 miRNA-target gene interactions involved in bone fracture healing were identified. A novel scoring system was designed to analyze the miRNA contribution to impaired fracture healing (RCIFH). Using this method, 11 novel miRNAs were identified to impair fracture healing at 2- or 4-week post-fracture. Thereafter, function analysis of target genes was performed for miRNAs with high RCIFH values. The results showed that high RCIFH miRNAs in aged female mice might impair fracture healing not only by down-regulating angiogenesis-, chondrogenesis-, and osteogenesis-related pathways, but also by up-regulating osteoclastogenesis-related pathway, which implied the essential roles of these high RCIFH miRNAs in impaired fracture healing in aged females, and might promote the discovery of novel therapeutic strategies. PMID:27527150

  17. Targeted mutagenesis in sea urchin embryos using TALENs.

    PubMed

    Hosoi, Sayaka; Sakuma, Tetsushi; Sakamoto, Naoaki; Yamamoto, Takashi

    2014-01-01

    Genome editing with engineered nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) has been reported in various animals. We previously described ZFN-mediated targeted mutagenesis and insertion of reporter genes in sea urchin embryos. In this study, we demonstrate that TALENs can induce mutagenesis at specific genomic loci of sea urchin embryos. Injection of TALEN mRNAs targeting the HpEts transcription factor into fertilized eggs resulted in the impairment of skeletogenesis. Sequence analyses of the mutations showed that deletions and/or insertions occurred at the HpEts target site in the TALEN mRNAs-injected embryos. The results suggest that targeted gene disruption using TALENs is feasible in sea urchin embryos. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  18. Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

    PubMed

    Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

    2018-05-03

    People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

  19. A new approach to data evaluation in the non-target screening of organic trace substances in water analysis.

    PubMed

    Müller, Alexander; Schulz, Wolfgang; Ruck, Wolfgang K L; Weber, Walter H

    2011-11-01

    Non-target screening via high performance liquid chromatography-mass spectrometry (HPLC-MS) has gained increasingly in importance for monitoring organic trace substances in water resources targeted for the production of drinking water. In this article a new approach for evaluating the data from non-target HPLC-MS screening in water is introduced and its advantages are demonstrated using the supply of drinking water as an example. The crucial difference between this and other approaches is the comparison of samples based on compounds (features) determined by their full scan data. In so doing, we take advantage of the temporal, spatial, or process-based relationships among the samples by applying the set operators, UNION, INTERSECT, and COMPLEMENT to the features of each sample. This approach regards all compounds, detectable by the used analytical method. That is the fundamental meaning of non-target screening, which includes all analytical information from the applied technique for further data evaluation. In the given example, in just one step, all detected features (1729) of a landfill leachate sample could be examined for their relevant influences on water purification respectively drinking water. This study shows that 1721 out of 1729 features were not relevant for the water purification. Only eight features could be determined in the untreated water and three of them were found in the final drinking water after ozonation. In so doing, it was possible to identify 1-adamantylamine as contamination of the landfill in the drinking water at a concentration in the range of 20 ng L(-1). To support the identification of relevant compounds and their transformation products, the DAIOS database (Database-Assisted Identification of Organic Substances) was used. This database concept includes some functions such as product ion search to increase the efficiency of the database query after the screening. To identify related transformation products the database function

  20. Targeting Virus-host Interactions of HIV Replication.

    PubMed

    Weydert, Caroline; De Rijck, Jan; Christ, Frauke; Debyser, Zeger

    2016-01-01

    Cellular proteins that are hijacked by HIV in order to complete its replication cycle, form attractive new targets for antiretroviral therapy. In particular, the protein-protein interactions between these cellular proteins (cofactors) and viral proteins are of great interest to develop new therapies. Research efforts have led to the validation of different cofactors and some successes in therapeutic applications. Maraviroc, the first cofactor inhibitor approved for human medicinal use, provided a proof of concept. Furthermore, compounds developed as Integrase-LEDGF/p75 interaction inhibitors (LEDGINs) have advanced to early clinical trials. Other compounds targeting cofactors and cofactor-viral protein interactions are currently under development. Likewise, interactions between cellular restriction factors and their counteracting HIV protein might serve as interesting targets in order to impair HIV replication. In this respect, compounds targeting the Vif-APOBEC3G interaction have been described. In this review, we focus on compounds targeting the Integrase- LEDGF/p75 interaction, the Tat-P-TEFb interaction and the Vif-APOBEC3G interaction. Additionally we give an overview of currently discovered compounds presumably targeting cellular cofactor-HIV protein interactions.

  1. Impaired memory updating associated with impaired recall of negative words in dysphoric rumination-Evidence for a removal deficit.

    PubMed

    Chang, Ee Pin; Ecker, Ullrich K H; Page, Andrew C

    2017-06-01

    We present evidence that dysphoric rumination involves a working memory (WM) updating deficit. Sixty-one undergraduates-pre-screened with rumination and depression scales-completed a novel task providing a specific measure of WM updating. This task involved the substitution of emotionally-valenced words, and provided an online measure of the time taken to remove outdated items from WM. Results showed that dysphoric ruminators spent less time removing outdated words from WM when the new to-be-remembered word was negative. This effect was (1) associated with impaired subsequent recall of negative words, arguably caused by interference from the insufficiently removed outdated words; and (2) correlated with participants' rumination scores. This is the first study to use the novel removal task to investigate the nature of WM-updating impairments in rumination. The findings are consistent with a negative attentional bias in rumination, and provide preliminary evidence that rumination is associated with a valence-generic removal deficit during WM updating. Reducing the attentional bias could thus be an intervention target in the treatment of dysphoric rumination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms

    PubMed Central

    Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

    2014-01-01

    Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference “Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms” convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants. PMID:24637519

  3. Focal Scn1a knockdown induces cognitive impairment without seizures

    PubMed Central

    Bender, Alex C.; Natola, Heather; Holmes, Gregory L.; Scott, Rod C.; Lenck-Santini, Pierre-Pascal

    2013-01-01

    Cognitive impairment is a common comorbidity in pediatric epilepsy that can severely affect quality of life. In many cases, antiepileptic treatments fail to improve cognition. Therefore, a fundamental question is whether underlying brain abnormalities may contribute to cognitive impairment through mechanisms independent of seizures. Here, we examined the possible effects on cognition of Nav1.1 down-regulation, a sodium channel principally involved in Dravet syndrome but also implicated in other cognitive disorders, including autism and Alzheimer’s disease. Using an siRNA approach to knockdown Nav1.1 selectively in the basal forebrain region, we were able to target a learning and memory network while avoiding the generation of spontaneous seizures. We show that reduction of Nav1.1 expression in the medial septum and diagonal band of Broca leads to a dysregulation of hippocampal oscillations in association with a spatial memory deficit. We propose that the underlying etiology responsible for Dravet syndrome may directly contribute to cognitive impairment in a manner that is independent from seizures. PMID:23318929

  4. Mechanistic Insights from Vascular and Cardiac Impairments in Rats Inhaling Diesel Exhaust Particles and Ozone

    EPA Science Inventory

    Although the causality has been established between air pollution and cardiovascular impairments, the molecular mechanisms are unknown. Moreover, cardiovascular effects of ozone have not been studied until recently. We hypothesize that vasculature and cardiac tissues are targets ...

  5. Effect of the entomopathogenic fungus Lecanicillium muscariumon the predatory mite Phytoseiulus persimilis as a non-target organism.

    PubMed

    Donka, András; Sermann, Helga; Büttner, Carmen

    2008-01-01

    In biological control, different benefit organisms have to combine for an effective management. If entomopathogenic fungi will be integrated, than it has to be considered also the effect on non-target organisms Like beneficial arthropods. Because of the high importance of predatory mite Phytoseiulus persimilis in biological control it was to determine side effects of Leconicillium muscarium on this species. In two standardised biotests in petri dish and on plants (P. vulgaris) individuals were dipped in suspension or set down on leafs after spraying with L. muscarium at different spore density. Results indicate pathogenicity for the predatory mite in principle. But the dimension of infection risk decrease, all the more conditions approach to practical sequence. Under practical conditions on plants and in practical relevant concentration of 10(6) and 10(7) sp./ml no risk is to expect on the plant.

  6. Impairment Rating Ambiguity in the United States: The Utah Impairment Guides for Calculating Workers' Compensation Impairments

    PubMed Central

    Hunter, Bradley; Bunkall, Larry D.; Holmes, Edward B.

    2009-01-01

    Since the implementation of workers' compensation, accurately and consistently rating impairment has been a concern for the employee and employer, as well as rating physicians. In an attempt to standardize and classify impairments, the American Medical Association (AMA) publishes the AMA Guides ("Guides"), and recently published its 6th edition of the AMA Guides. Common critiques of the AMA Guides 6th edition are that they are too complex, lacking in evidence-based methods, and rarely yield consistent ratings. Many states mandate use of some edition of the AMA Guides, but few states are adopting the current edition due to the increasing difficulty and frustration with their implementation. A clearer, simpler approach is needed. Some states have begun to develop their own supplemental guides to combat problems in complexity and validity. Likewise studies in Korea show that past methods for rating impairment are outdated and inconsistent, and call for measures to adapt current methods to Korea's specific needs. The Utah Supplemental Guides to the AMA Guides have been effective in increasing consistency in rating impairment. It is estimated that litigation of permanent impairment has fallen below 1% and Utah is now one of the least costly states for obtaining workers' compensation insurance, while maintaining a medical fee schedule above the national average. Utah's guides serve as a model for national or international impairment guides. PMID:19503678

  7. Chronic inflammation and impaired development of the preterm brain.

    PubMed

    Bennet, Laura; Dhillon, Simerdeep; Lear, Chris A; van den Heuij, Lotte; King, Victoria; Dean, Justin M; Wassink, Guido; Davidson, Joanne O; Gunn, Alistair Jan

    2018-02-01

    The preterm newborn is at significant risk of neural injury and impaired neurodevelopment. Infants with mild or no evidence of injury may also be at risk of altered brain development, with evidence impaired cell maturation. The underlying causes are multifactorial and include exposure of both the fetus and newborn to hypoxia-ischemia, inflammation (chorioamnionitis) and infection, adverse maternal lifestyle choices (smoking, drug and alcohol use, diet) and obesity, as well as the significant demand that adaptation to post-natal life places on immature organs. Further, many fetuses and infants may have combinations of these events, and repeated (multi-hit) events that may induce tolerance to injury or sensitize to greater injury. Currently there are no treatments to prevent preterm injury or impaired neurodevelopment. However, inflammation is a common pathway for many of these insults, and clinical and experimental evidence demonstrates that acute and chronic inflammation is associated with impaired brain development. This review examines our current knowledge about the relationship between inflammation and preterm brain development, and the potential for stem cell therapy to provide neuroprotection and neurorepair through reducing inflammation and release of trophic factors, which promote cell maturation and repair. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Electrohypersensitivity: a functional impairment due to an inaccessible environment.

    PubMed

    Johansson, Olle

    2015-01-01

    In Sweden, electrohypersensitivity is recognized as a functional impairment which implies only the environment as the culprit. The Swedish view provides persons with this impairment a maximal legal protection, it gives them the right to get accessibility measures for free, as well as governmental subsidies and municipality economic support, and to provide them with special Ombudsmen (at the municipality, the EU, and the UN level, respectively), the right and economic means to form disability organizations and allow these to be part of national and international counterparts, all with the simple and single aim to allow persons with the functional impairment electrohypersensitivity to live an equal life in a society based on equality. They are not seen as patients, the do not have an overriding medical diagnosis, but the 'patient' is only the inferior and potentially toxic environment. This does not mean that a subjective symptom of a functionally impaired can not be treated by a physician, as well as get sick-leave from their workplace as well as economic compensation, and already in the year 2000 such symptoms were identified in the Internal Code of Diagnoses, version 10 (ICD-10; R68.8/now W90), and have been since. But the underlying cause still remains only the environment.

  9. Learning Building Layouts with Non-geometric Visual Information: The Effects of Visual Impairment and Age

    PubMed Central

    Kalia, Amy A.; Legge, Gordon E.; Giudice, Nicholas A.

    2009-01-01

    Previous studies suggest that humans rely on geometric visual information (hallway structure) rather than non-geometric visual information (e.g., doors, signs and lighting) for acquiring cognitive maps of novel indoor layouts. This study asked whether visual impairment and age affect reliance on non-geometric visual information for layout learning. We tested three groups of participants—younger (< 50 years) normally sighted, older (50–70 years) normally sighted, and low vision (people with heterogeneous forms of visual impairment ranging in age from 18–67). Participants learned target locations in building layouts using four presentation modes: a desktop virtual environment (VE) displaying only geometric cues (Sparse VE), a VE displaying both geometric and non-geometric cues (Photorealistic VE), a Map, and a Real building. Layout knowledge was assessed by map drawing and by asking participants to walk to specified targets in the real space. Results indicate that low-vision and older normally-sighted participants relied on additional non-geometric information to accurately learn layouts. In conclusion, visual impairment and age may result in reduced perceptual and/or memory processing that makes it difficult to learn layouts without non-geometric visual information. PMID:19189732

  10. Pharyngeal cavity and the gills are the target organ for the repellent action of pardaxin in shark.

    PubMed

    Primor, N

    1985-05-15

    Pardaxin, an active principle of the repellent secretion of the Red Sea flatfish, Pardachirus marmoratus, elicited severe struggling, mouth paralysis, and transient increase in urea leakage from the gills only when administered to the medium bathing the shark's pharyngeal cavity and gills. An apparatus was constructed which prevents a mixing of the outflow from shark's gills with water bathing its surface skin. It is concluded that in sharks the gills and/or the pharyngeal cavity are the target organ for the repellent action of pardaxin.

  11. Telephone Crisis Support Workers' Intentions to Use Recommended Skills While Experiencing Functional Impairment.

    PubMed

    Kitchingman, Taneile A; Wilson, Coralie J; Woodward, Alan; Caputi, Peter; Wilson, Ian

    2018-05-01

    Empathic engagement with distressed others can lead to elevated symptoms of psychological distress and functional impairment, which preclude helping professionals' delivery of optimal patient care. Whether telephone crisis support workers are impacted in a similar way is not currently reported in the literature. This study examined the relationship between functional impairment and intentions to use recommended support skills in a representative national sample of 210 telephone crisis support workers. Participants completed an online survey including measures of functional impairment and intentions to use recommended telephone crisis support skills with callers reporting suicidal ideation, symptoms of depression, and anxiety. As a group, participants who experienced greater functional impairment during the past month reported significantly lower intentions to use recommended support skills with callers than those who reported lower functional impairment. Future research is needed to clarify the extent to which results generalize to telephone crisis support workers from other organizations. Results warrant further research to (a) identify determinants of telephone crisis support workers' functional impairment, and (b) for the deliberate management of telephone crisis support workers' functional impairment through developing and/or modifying existing service strategies to optimize workers' psychological well-being and delivery of support to callers.

  12. Visual target modulation of functional connectivity networks revealed by self-organizing group ICA.

    PubMed

    van de Ven, Vincent; Bledowski, Christoph; Prvulovic, David; Goebel, Rainer; Formisano, Elia; Di Salle, Francesco; Linden, David E J; Esposito, Fabrizio

    2008-12-01

    We applied a data-driven analysis based on self-organizing group independent component analysis (sogICA) to fMRI data from a three-stimulus visual oddball task. SogICA is particularly suited to the investigation of the underlying functional connectivity and does not rely on a predefined model of the experiment, which overcomes some of the limitations of hypothesis-driven analysis. Unlike most previous applications of ICA in functional imaging, our approach allows the analysis of the data at the group level, which is of particular interest in high order cognitive studies. SogICA is based on the hierarchical clustering of spatially similar independent components, derived from single subject decompositions. We identified four main clusters of components, centered on the posterior cingulate, bilateral insula, bilateral prefrontal cortex, and right posterior parietal and prefrontal cortex, consistently across all participants. Post hoc comparison of time courses revealed that insula, prefrontal cortex and right fronto-parietal components showed higher activity for targets than for distractors. Activation for distractors was higher in the posterior cingulate cortex, where deactivation was observed for targets. While our results conform to previous neuroimaging studies, they also complement conventional results by showing functional connectivity networks with unique contributions to the task that were consistent across subjects. SogICA can thus be used to probe functional networks of active cognitive tasks at the group-level and can provide additional insights to generate new hypotheses for further study. Copyright 2007 Wiley-Liss, Inc.

  13. How Do Children with Phonological Impairment Respond to Requests for Clarification Containing Polysyllables?

    ERIC Educational Resources Information Center

    Masso, Sarah; McCabe, Patricia; Baker, Elise

    2014-01-01

    Accurate production of polysyllables (words of three or more syllables) can be challenging for children with phonological impairment. Research with typically developing children has suggested that children can improve their polysyllable productions in response to requests for clarification containing an incorrect model of a target word (Gozzard et…

  14. Implementing SFAS No 121: Accounting for Impaired Assets.

    PubMed

    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.

  15. Internal shifting impairments in response to emotional information in dysphoric adolescents.

    PubMed

    Wante, Laura; Mueller, Sven C; Demeyer, Ineke; Naets, Tiffany; Braet, Caroline

    2017-12-01

    Previous studies have suggested that internal cognitive control impairments may play an important role in the development of depression. Despite a growing body of research in adults, the ability to shift internal attention between mental representations in working memory has received little attention in younger populations. This study investigated internal shifting capacity between emotional and non-emotional information in dysphoric and non-dysphoric adolescents. Twenty dysphoric and 34 non-dysphoric adolescents (10-17 years) completed an Internal Shifting Task, with pictures of angry and neutral faces, to measure the ability to shift attention between information held in working memory. Dysphoric adolescents showed specific shifting impairments when processing emotional material relative to non-dysphoric adolescents. Valence-specific analyses revealed that shifting was particularly impaired when shifting from negative to neutral information. By comparison, relative to non-dysphoric adolescents, dysphoric adolescents did not show shifting impairments when non-emotional features of the pictures had to be processed. The study is limited by the absence of a structured clinical interview as dysphoria was determined dimensionally. Furthermore, a comparison of the effects of different negative stimuli on shifting could not be made since sad stimuli were not included in the stimulus set. The results confirm the link between depressive symptoms and emotion-specific shifting impairments in adolescents and indicate that targeting shifting ability in response to emotional stimuli may be a promising avenue for prevention programs. Longitudinal research is needed to replicate results and to explore the role of internal shifting impairments in the etiology and maintenance of depression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Gender, depression and physical impairment: an epidemiologic perspective from Aleppo, Syria

    PubMed Central

    Rastam, Samer; Ward, Kenneth D.; Maziak, Wasim

    2010-01-01

    Objective Examine the association of physical impairment with gender, depression, and socio-demographics in the community in Aleppo, Syria. Method We conducted a cross-sectional, population-based study in Aleppo on adults aged 18–65 (N = 2,038). We used a computerized interviewer-administered structured questionnaire. Physical impairment was measured via an adapted 12-item World Health Organization, Health State Description Individual Questionnaire which includes both physical and emotional items. We used physical impairment items score to classify individuals into low, middle, and high physical impairment category. Self-report of physician-diagnosed depression and chronic diseases active in the past year and their current treatment status were obtained. Results Sample mean age (SD) was 35.3 (12.1) years, 55% were female, and 4.5% had depression. Female gender, low socioeconomic status (SES), and depression were associated with high physical impairment. Women had more impairment (OR = 3.35, 95% CI: 2.15–5.21) with little change after controlling for depression and chronic diseases, but significantly decreased after controlling for socio-demographics (OR = 1.51, 95% CI: 0.84–2.73). The association with low (vs. high) SES was prominent (OR = 2.48, 95% CI: 1.32–4.67) after controlling for all variables. Depression’s association (OR = 4.85, 95% CI: 1.93–12.15) lost significance after controlling for chronic diseases (OR = 2.81, 95% CI: 0.96–8.25), but further adjustment for socio-demographics had little effect. Conclusion Women and individuals of low SES appear more vulnerable to physical impairment in the community in Aleppo. Depression’s association with physical impairment may be mediated through co-existing chronic diseases. Public health planning regarding physical impairment in Syria should encompass these as putative risk factors. PMID:20195569

  17. Synthetic PAMAM-RGD conjugates target and bind to odontoblast-like MDPC 23 cells and the predentin in tooth organ cultures.

    PubMed

    Hill, Elliott; Shukla, Rameshwer; Park, Steve S; Baker, James R

    2007-01-01

    Screening techniques now allow for the identification of small peptides that bind specifically to molecules like cells. However, despite the enthusiasm for this approach, single peptides often lack the binding affinity to target in vivo and regulate cell function. We took peptides containing the Arg-Gly Asp(RGD) motif that bind to the alpha Vbeta 3 integrin and have shown potential as therapeutics. To improve their binding affinity, we synthesized polyamidoamine (PAMAM) dendrimer-RGD conjugates that that contain 12-13 copies of the peptide. When cultured with human dermal microvessel endothelial cells (HDMEC), human vascular endothelial cells (HUVEC), or odontoblast-like MDPC-23 cells, the PAMAM dendrimer conjugate targets this receptor in a manner that is both time- and dose-dependent. Finally, this conjugate selectively targets RGD binding sites in the predentin of human tooth organ cultures. Taken together, these studies provide proof of principle that synthetic PAMAM-RGD conjugates could prove useful as carriers for the tissue-specific delivery of integrin-targeted therapeutics or imaging agents and could be used to engineer tissue regeneration.

  18. A Computer Supported Teamwork Project for People with a Visual Impairment.

    ERIC Educational Resources Information Center

    Hale, Greg

    2000-01-01

    Discussion of the use of computer supported teamwork (CSTW) in team-based organizations focuses on problems that visually impaired people have reading graphical user interface software via screen reader software. Describes a project that successfully used email for CSTW, and suggests issues needing further research. (LRW)

  19. Edaravone attenuates intracerebroventricular streptozotocin-induced cognitive impairment in rats.

    PubMed

    Reeta, K H; Singh, Devendra; Gupta, Yogendra K

    2017-04-01

    Alzheimer's disease is a major cause of dementia worldwide. Edaravone, a potent free radical scavenger, is reported to be neuroprotective. The present study was designed to investigate the effect of chronic edaravone administration on intracerebroventricular-streptozotocin (ICV-STZ) induced cognitive impairment in male Wistar rats. Cognitive impairment was developed by single ICV-STZ (3 mg/kg) injection bilaterally on day 1. Edaravone (1, 3 and 10 mg/kg, orally, once daily) was administered for 28 days. Morris water maze and passive avoidance tests were used to assess cognitive functions at baseline and on days 14 and 28. ICV-STZ caused cognitive impairment as evidenced by increased escape latency and decreased time spent in target quadrant in the Morris water maze test and reduced retention latency in the passive avoidance test. STZ caused increase in oxidative stress, cholinesterases, inflammatory cytokines and protein expression of ROCK-II and decrease in protein expression of ChAT. Edaravone ameliorated the STZ-induced cognitive impairment. STZ-induced increase in oxidative stress and increased levels of pro-inflammatory cytokines (TNF-α, IL-1β) were mitigated by edaravone. Edaravone also prevented STZ-induced increased protein expression of ROCK-II. Moreover, edaravone significantly prevented STZ-induced increased activity of cholinesterases in the cortex and hippocampus. The decreased expression of ChAT caused by STZ was brought towards normal by edaravone in the hippocampus. The results thus show that edaravone is protective against STZ-induced cognitive impairment, oxidative stress, cholinergic dysfunction and altered protein expressions. This study thus suggests the potential of edaravone as an adjuvant in the treatment of Alzheimer's disease. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice.

    PubMed

    Hou, Yue; Xie, Guanbo; Liu, Xia; Li, Guoxun; Jia, Congcong; Xu, Jinghua; Wang, Bing

    2016-03-01

    The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown. This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice. Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines. Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group. Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.

  1. Potential of targeting TGF-β for organ transplant patients

    PubMed Central

    Iwashima, Makio; Love, Robert

    2015-01-01

    TGF-β was originally considered as an immunoregulatory cytokine, but accumulating data demonstrate that it also plays a critical role in development of effector immunity. Since TGF-β has a potent ability to alter immune responses, modulation of the TGF-β pathway for treatment of transplantation patients could be effective if carried out in a target selective manner. This review will focus on the role of TGF-β in T cell differentiation and discuss the prospect of TGF-β as the therapeutic target of lung transplantation acceptance. PMID:23464518

  2. First steps in designing an all-in-one ICT-based device for persons with cognitive impairment: evaluation of the first mock-up.

    PubMed

    Boman, Inga-Lill; Persson, Ann-Christine; Bartfai, Aniko

    2016-03-07

    This project Smart Assisted Living involving Informal careGivers++ (SALIG) intends to develop an ICT-based device for persons with cognitive impairment combined with remote support possibilities for significant others and formal caregivers. This paper presents the identification of the target groups' needs and requirements of such device and the evaluation of the first mock-up, demonstrated in a tablet. The inclusive design method that includes end-users in the design process was chosen. First, a scoping review was conducted in order to examine the target group's need of an ICT-based device, and to gather recommendations regarding its design and functionalities. In order to capture the users' requirements of the design and functionalities of the device three targeted focus groups were conducted. Based on the findings from the publications and the focus groups a user requirement specification was developed. After that a design concept and a first mock-up was developed in an iterative process. The mock-up was evaluated through interviews with persons with cognitive impairment, health care professionals and significant others. Data were analysed using content analysis. Several useful recommendations of the design and functionalities of the SALIG device for persons with cognitive impairment were identified. The main benefit of the mock-up was that it was a single device with a set of functionalities installed on a tablet and designed for persons with cognitive impairment. An additional benefit was that it could be used remotely by significant others and formal caregivers. The SALIG device has the potentials to facilitate everyday life for persons with cognitive impairment, their significant others and the work situation for formal caregivers. The results may provide guidance in the development of different types of technologies for the target population and for people with diverse disabilities. Further work will focus on developing a prototype to be empirically tested

  3. Neuroinflammatory Dynamics Underlie Memory Impairments after Repeated Social Defeat

    PubMed Central

    McKim, Daniel B.; Niraula, Anzela; Tarr, Andrew J.; Wohleb, Eric S.

    2016-01-01

    various cognitive and mood disorders that impair everyday functioning and overall quality of life. The brain, previously thought of as an immune-privileged organ, is now known to communicate extensively with the peripheral immune system. This brain–body communication plays a significant role in various stress-induced inflammatory conditions, also characterized by psychological impairments. Findings from this study implicate neuroimmune activation rather than impaired neurogenesis in stress-induced cognitive deficits. This idea opens up possibilities for novel immune interventions in the treatment of cognitive and mood disturbances, while also adding to the complexity surrounding the functional implications of adult neurogenesis. PMID:26937001

  4. Neuroinflammatory Dynamics Underlie Memory Impairments after Repeated Social Defeat.

    PubMed

    McKim, Daniel B; Niraula, Anzela; Tarr, Andrew J; Wohleb, Eric S; Sheridan, John F; Godbout, Jonathan P

    2016-03-02

    disorders that impair everyday functioning and overall quality of life. The brain, previously thought of as an immune-privileged organ, is now known to communicate extensively with the peripheral immune system. This brain-body communication plays a significant role in various stress-induced inflammatory conditions, also characterized by psychological impairments. Findings from this study implicate neuroimmune activation rather than impaired neurogenesis in stress-induced cognitive deficits. This idea opens up possibilities for novel immune interventions in the treatment of cognitive and mood disturbances, while also adding to the complexity surrounding the functional implications of adult neurogenesis. Copyright © 2016 the authors 0270-6474/16/362590-15$15.00/0.

  5. Pioneering topological methods for network-based drug-target prediction by exploiting a brain-network self-organization theory.

    PubMed

    Durán, Claudio; Daminelli, Simone; Thomas, Josephine M; Haupt, V Joachim; Schroeder, Michael; Cannistraci, Carlo Vittorio

    2017-04-26

    The bipartite network representation of the drug-target interactions (DTIs) in a biosystem enhances understanding of the drugs' multifaceted action modes, suggests therapeutic switching for approved drugs and unveils possible side effects. As experimental testing of DTIs is costly and time-consuming, computational predictors are of great aid. Here, for the first time, state-of-the-art DTI supervised predictors custom-made in network biology were compared-using standard and innovative validation frameworks-with unsupervised pure topological-based models designed for general-purpose link prediction in bipartite networks. Surprisingly, our results show that the bipartite topology alone, if adequately exploited by means of the recently proposed local-community-paradigm (LCP) theory-initially detected in brain-network topological self-organization and afterwards generalized to any complex network-is able to suggest highly reliable predictions, with comparable performance with the state-of-the-art-supervised methods that exploit additional (non-topological, for instance biochemical) DTI knowledge. Furthermore, a detailed analysis of the novel predictions revealed that each class of methods prioritizes distinct true interactions; hence, combining methodologies based on diverse principles represents a promising strategy to improve drug-target discovery. To conclude, this study promotes the power of bio-inspired computing, demonstrating that simple unsupervised rules inspired by principles of topological self-organization and adaptiveness arising during learning in living intelligent systems (like the brain) can efficiently equal perform complicated algorithms based on advanced, supervised and knowledge-based engineering. © The Author 2017. Published by Oxford University Press.

  6. Pragmatic Language Development in Language Impaired and Typically Developing Children: Incorrect Answers in Context

    ERIC Educational Resources Information Center

    Ryder, Nuala; Leinonen, Eeva

    2014-01-01

    This study focused on young children's incorrect answers to pragmatically demanding questions. Children with specific language impairment (SLI), including a subgroup with pragmatic language difficulties (PLD) and typically developing children answered questions targeting implicatures, based on a storybook and short verbal scenarios.…

  7. Visual Impairment

    MedlinePlus

    ... site Sitio para adolescentes Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Visual Impairment KidsHealth / For Teens / Visual Impairment What's in ...

  8. Different Patterns of Theory of Mind Impairment in Mild Cognitive Impairment.

    PubMed

    Moreau, Noémie; Rauzy, Stéphane; Bonnefoi, Bernadette; Renié, Laurent; Martinez-Almoyna, Laurent; Viallet, François; Champagne-Lavau, Maud

    2015-01-01

    Theory of Mind refers to the ability to infer other’s mental states, their beliefs, intentions, or knowledge. To date, only two studies have reported the presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the present study,we evaluated 20 MCI patients and compared them with 25 healthy control participants using two Theory of Mind tasks. The first task was a false belief paradigm as frequently used in the literature, and the second one was a referential communication task,assessing Theory of Mind in a real situation of interaction and which had never been used before in this population. The results showed that MCI patients presented difficulties inferring another person’s beliefs about reality and attributing knowledge to them in a situation of real-life interaction. Two different patterns of Theory of Mind emerged among the patients. In comparison with the control group, some MCI patients demonstrated impairment only in the interaction task and presented isolated episodicmemory impairment, while others were impaired in both Theory of Mind tasks and presented cognitive impairment impacting both episodic memory and executive functioning. Theory of Mind is thus altered in the very early stages of cognitive impairment even in real social interaction, which could impact precociously relationships in daily life.

  9. Food experiences and eating patterns of visually impaired and blind people.

    PubMed

    Bilyk, Marie Claire; Sontrop, Jessica M; Chapman, Gwen E; Barr, Susan I; Mamer, Linda

    2009-01-01

    The number of visually impaired and blind Canadians will rise dramatically as our population ages, and yet little is known about the impact of blindness on the experience of food and eating. In this qualitative study, the food experiences and eating patterns of visually impaired and blind people were examined. Influencing factors were also explored. In 2000, nine blind or severely visually impaired subjects were recruited through blindness-related organizations in British Columbia. Participants completed individual semi-structured, in-depth interviews. These were transcribed verbatim, coded, and analyzed to explicate participants' experiences. Participants experienced blindness-related obstacles when shopping for food, preparing food, and eating in restaurants. Inaccessible materials and environments left participants with a diet lacking in variety and limited access to physical activity. Seven participants were overweight or obese, a finding that may be related to limited physical activity and higher-than-average restaurant use. This is the first study in which the experience of food and eating is described from the perspective of visually impaired Canadians. Nutrition and blindness professionals must work together to reduce the food-related obstacles faced by visually impaired and blind people. Professionals must address both individual skill development and social and structural inequities.

  10. Ophthalmic Manifestations and Causes of Vision Impairment in Ebola Virus Disease Survivors in Monrovia, Liberia.

    PubMed

    Shantha, Jessica G; Crozier, Ian; Hayek, Brent R; Bruce, Beau B; Gargu, Catherine; Brown, Jerry; Fankhauser, John; Yeh, Steven

    2017-02-01

    To describe the ocular findings, visual impairment, and association of structural complications of uveitis with visual impairment in a cohort of survivors of Ebola virus disease (EVD) in Monrovia, Liberia. Retrospective, uncontrolled, cross-sectional study. Survivors of EVD who were evaluated in an ophthalmology clinic at Eternal Love Winning Africa (ELWA) Hospital in Monrovia, Liberia. A cohort of EVD survivors who underwent baseline ophthalmic evaluation at ELWA Hospital were retrospectively reviewed for demographic information, length of Ebola treatment unit (ETU) stay, visual acuity (VA), and ophthalmic examination findings. For patients with uveitis, disease activity (active vs. inactive) and grade of inflammation were recorded according to Standardization of Uveitis Nomenclature criteria. The level of VA impairment was categorized according to World Health Organization classification for VA impairment as follows: normal/mild, VA 20/70 or better; moderate, VA 20/70-20/200; severe, VA 20/200-20/400; blindness, VA <20/400. Visual acuity, length of ETU stay, and structural complications were compared between EVD survivors with and without uveitis. Structural complications associated with moderate VA impairment or poorer were analyzed. Frequency of ocular complications including uveitis and optic neuropathy in EVD survivors, level of VA impairment in EVD survivors with uveitis, and structural complications associated with VA impairment in EVD survivors. A total of 96 survivors of EVD were examined. A total of 21 patients developed an EVD-associated uveitis, and 3 patients developed an EVD-associated optic neuropathy. Visual acuity was blind (VA >20/400) in 38.5% of eyes with uveitis. Anatomic subtypes of uveitis included anterior, posterior, and panuveitis in 2, 13, and 6 patients, respectively. Examination findings associated with at least moderate visual impairment by World Health Organization criteria (VA <20/70) included keratic precipitates (P < 0

  11. Obesity Impairs Skeletal Muscle Regeneration Through Inhibition of AMPK.

    PubMed

    Fu, Xing; Zhu, Meijun; Zhang, Shuming; Foretz, Marc; Viollet, Benoit; Du, Min

    2016-01-01

    Obesity is increasing rapidly worldwide and is accompanied by many complications, including impaired muscle regeneration. The obese condition is known to inhibit AMPK activity in multiple tissues. We hypothesized that the loss of AMPK activity is a major reason for hampered muscle regeneration in obese subjects. We found that obesity inhibits AMPK activity in regenerating muscle, which was associated with impeded satellite cell activation and impaired muscle regeneration. To test the mediatory role of AMPKα1, we knocked out AMPKα1 and found that both proliferation and differentiation of satellite cells are reduced after injury and that muscle regeneration is severely impeded, reminiscent of hampered muscle regeneration seen in obese subjects. Transplanted satellite cells with AMPKα1 deficiency had severely impaired myogenic capacity in regenerating muscle fibers. We also found that attenuated muscle regeneration in obese mice is rescued by AICAR, a drug that specifically activates AMPK, but AICAR treatment failed to improve muscle regeneration in obese mice with satellite cell-specific AMPKα1 knockout, demonstrating the importance of AMPKα1 in satellite cell activation and muscle regeneration. In summary, AMPKα1 is a key mediator linking obesity and impaired muscle regeneration, providing a convenient drug target to facilitate muscle regeneration in obese populations. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.

    PubMed

    Feng, Xiaodong; Yang, Shanli; Liu, Jiao; Huang, Jia; Peng, Jun; Lin, Jiumao; Tao, Jing; Chen, Lidian

    2013-05-01

    Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.

  13. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    PubMed

    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.

  14. School Based Factors Affecting Learning of Kenyan Sign Language in Primary Schools for Hearing Impaired in Embu and Isiolo Counties, Kenya

    ERIC Educational Resources Information Center

    Rwaimba, Samuel Muthomi

    2016-01-01

    This was a descriptive survey study design which sought to establish the school based factors that affect the learning of Kenyan Sign Language in primary schools for learners with hearing impairment in Embu and Isiolo counties in Kenya. The target population was all teachers teaching in primary schools for learners with hearing impairment in the…

  15. Association between alcohol-impaired driving enforcement-related strategies and alcohol-impaired driving.

    PubMed

    Sanem, Julia R; Erickson, Darin J; Rutledge, Patricia C; Lenk, Kathleen M; Nelson, Toben F; Jones-Webb, Rhonda; Toomey, Traci L

    2015-05-01

    All states in the U.S. prohibit alcohol-impaired driving but active law enforcement is necessary for effectively reducing this behavior. Sobriety checkpoints, saturation patrols, open container laws, and media campaigns related to enforcement efforts are all enforcement-related strategies for reducing alcohol-impaired driving. We conducted surveys of all state patrol agencies and a representative sample of local law enforcement agencies to assess their use of alcohol-impaired driving enforcement-related strategies and to determine the relationship between these enforcement-related strategies and self-reported alcohol-impaired driving behavior obtained from the Behavioral Risk Factor Surveillance System. We found that sobriety checkpoints, saturation patrols, and enforcement of open container laws were associated with a lower prevalence of alcohol-impaired driving but, more importantly, a combination of enforcement-related strategies was associated with a greater decrease in alcohol-impaired driving than any individual enforcement-related activity. In addition, alcohol-impaired driving enforcement-related strategies were associated with decreased alcohol-impaired driving above and beyond their association with decreased binge drinking. Results suggest law enforcement agencies should give greater priority to using a combination of strategies rather than relying on any one individual enforcement activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Sports, Outdoor Recreation, and Games for Visually and Physically Impaired Individuals: Reference Circular No. 91-1.

    ERIC Educational Resources Information Center

    Library of Congress, Washington, DC. National Library Service for the Blind and Physically Handicapped.

    This resource guide lists and describes print materials, nonprint materials, and organizations dealing with sports, outdoor recreation, and games for visually and physically impaired individuals. Section I focuses on national organizations that sponsor athletic events on various levels and provide related services for children, youth, and adults…

  17. Fabrication of 14 different RNA nanoparticles for specific tumor targeting without accumulation in normal organs

    PubMed Central

    Shu, Yi; Haque, Farzin; Shu, Dan; Li, Wei; Zhu, Zhenqi; Kotb, Malak; Lyubchenko, Yuri; Guo, Peixuan

    2013-01-01

    Due to structural flexibility, RNase sensitivity, and serum instability, RNA nanoparticles with concrete shapes for in vivo application remain challenging to construct. Here we report the construction of 14 RNA nanoparticles with solid shapes for targeting cancers specifically. These RNA nanoparticles were resistant to RNase degradation, stable in serum for >36 h, and stable in vivo after systemic injection. By applying RNA nanotechnology and exemplifying with these 14 RNA nanoparticles, we have established the technology and developed “toolkits” utilizing a variety of principles to construct RNA architectures with diverse shapes and angles. The structure elements of phi29 motor pRNA were utilized for fabrication of dimers, twins, trimers, triplets, tetramers, quadruplets, pentamers, hexamers, heptamers, and other higher-order oligomers, as well as branched diverse architectures via hand-in-hand, foot-to-foot, and arm-on-arm interactions. These novel RNA nanostructures harbor resourceful functionalities for numerous applications in nanotechnology and medicine. It was found that all incorporated functional modules, such as siRNA, ribozymes, aptamers, and other functionalities, folded correctly and functioned independently within the nanoparticles. The incorporation of all functionalities was achieved prior, but not subsequent, to the assembly of the RNA nanoparticles, thus ensuring the production of homogeneous therapeutic nanoparticles. More importantly, upon systemic injection, these RNA nanoparticles targeted cancer exclusively in vivo without accumulation in normal organs and tissues. These findings open a new territory for cancer targeting and treatment. The versatility and diversity in structure and function derived from one biological RNA molecule implies immense potential concealed within the RNA nanotechnology field. PMID:23604636

  18. Emerging therapies for gait disability and balance impairment: promises and pitfalls.

    PubMed

    Maetzler, Walter; Nieuwhof, Freek; Hasmann, Sandra E; Bloem, Bastiaan R

    2013-09-15

    Therapeutic management of gait and balance impairment during aging and neurodegeneration has long been a neglected topic. This has changed considerably during recent years, for several reasons: (1) an increasing recognition that gait and balance deficits are among the most relevant determinants of an impaired quality of life and increased mortality for affected individuals; (2) the arrival of new technology, which has allowed for new insights into the anatomy and functional (dis)integrity of gait and balance circuits; and (3) based in part on these improved insights, the development of new, more specific treatment strategies in the field of pharmacotherapy, deep brain surgery, and physiotherapy. The initial experience with these emerging treatments is encouraging, although much work remains to be done. The objective of this narrative review is to discuss several promising developments in the field of gait and balance treatment. We also address several pitfalls that can potentially hinder a fast and efficient continuation of this vital progress. Important issues that should be considered in future research include a clear differentiation between gait and balance as two distinctive targets for treatment and recognition of compensatory mechanisms as a separate target for therapeutic intervention. © 2013 Movement Disorder Society.

  19. The Use of Microcomputers in the Treatment of Cognitive-Communicative Impairments.

    ERIC Educational Resources Information Center

    Story, Tamara B.; Sbordone, Robert J.

    1988-01-01

    The use of microcomputer-assisted therapy as part of the total rehabilitation plan for brain-injured individuals with cognitive-communicative impairments is addressed. Design of effective computer-assisted remediation requires a careful decision-making process. Specific types of software are suggested for dealing with deficits in organization,…

  20. Target Organ Damage and Target Systolic Blood Pressure in Clinical Practice: The Campania Salute Network.

    PubMed

    D'Amato, Andrea; Mancusi, Costantino; Losi, Maria Angela; Izzo, Raffaele; Arnone, Maria Immacolata; Canciello, Grazia; Senese, Salvatore; De Luca, Nicola; de Simone, Giovanni; Trimarco, Bruno

    2018-05-07

    Lowering systolic blood pressure (SBP) below the conventional threshold (140 mm Hg) reduces left ventricular (LV) hypertrophy and incident cardiovascular (CV) events. We assessed whether different thresholds of SBP as the average value during follow-up (FU) have different impact on changes in target organ damage (TOD). From the Campania Salute Network registry, we selected 4,148 hypertensive patients with average SBP-FU <140 mm Hg, and without history of prevalent CV or chronic kidney disease (i.e.,

  1. Robot services for elderly with cognitive impairment: testing usability of graphical user interfaces.

    PubMed

    Granata, C; Pino, M; Legouverneur, G; Vidal, J-S; Bidaud, P; Rigaud, A-S

    2013-01-01

    Socially assistive robotics for elderly care is a growing field. However, although robotics has the potential to support elderly in daily tasks by offering specific services, the development of usable interfaces is still a challenge. Since several factors such as age or disease-related changes in perceptual or cognitive abilities and familiarity with computer technologies influence technology use they must be considered when designing interfaces for these users. This paper presents findings from usability testing of two different services provided by a social assistive robot intended for elderly with cognitive impairment: a grocery shopping list and an agenda application. The main goal of this study is to identify the usability problems of the robot interface for target end-users as well as to isolate the human factors that affect the use of the technology by elderly. Socio-demographic characteristics and computer experience were examined as factors that could have an influence on task performance. A group of 11 elderly persons with Mild Cognitive Impairment and a group of 11 cognitively healthy elderly individuals took part in this study. Performance measures (task completion time and number of errors) were collected. Cognitive profile, age and computer experience were found to impact task performance. Participants with cognitive impairment achieved the tasks committing more errors than cognitively healthy elderly. Instead younger participants and those with previous computer experience were faster at completing the tasks confirming previous findings in the literature. The overall results suggested that interfaces and contents of the services assessed were usable by older adults with cognitive impairment. However, some usability problems were identified and should be addressed to better meet the needs and capacities of target end-users.

  2. Electric crosstalk impairs spatial resolution of multi-electrode arrays in retinal implants

    NASA Astrophysics Data System (ADS)

    Wilke, R. G. H.; Khalili Moghadam, G.; Lovell, N. H.; Suaning, G. J.; Dokos, S.

    2011-08-01

    Active multi-electrode arrays are used in vision prostheses, including optic nerve cuffs and cortical and retinal implants for stimulation of neural tissue. For retinal implants, arrays with up to 1500 electrodes are used in clinical trials. The ability to convey information with high spatial resolution is critical for these applications. To assess the extent to which spatial resolution is impaired by electric crosstalk, finite-element simulation of electric field distribution in a simplified passive tissue model of the retina is performed. The effects of electrode size, electrode spacing, distance to target cells, and electrode return configuration (monopolar, tripolar, hexagonal) on spatial resolution is investigated in the form of a mathematical model of electric field distribution. Results show that spatial resolution is impaired with increased distance from the electrode array to the target cells. This effect can be partly compensated by non-monopolar electrode configurations and larger electrode diameters, albeit at the expense of lower pixel densities due to larger covering areas by each stimulation electrode. In applications where multi-electrode arrays can be brought into close proximity to target cells, as presumably with epiretinal implants, smaller electrodes in monopolar configuration can provide the highest spatial resolution. However, if the implantation site is further from the target cells, as is the case in suprachoroidal approaches, hexagonally guarded electrode return configurations can convey higher spatial resolution. This paper was originally submitted for the special issue containing contributions from the Sixth Biennial Research Congress of The Eye and the Chip.

  3. Natural products from marine organisms with neuroprotective activity in the experimental models of Alzheimer's disease, Parkinson's disease and ischemic brain stroke: their molecular targets and action mechanisms.

    PubMed

    Choi, Dong-Young; Choi, Hyukjae

    2015-02-01

    Continuous increases in the incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and brain stroke demand the urgent development of therapeutics. Marine organisms are well-known producers of natural products with diverse structures and pharmacological activities. Therefore, researchers have endeavored to identify marine natural products with neuroprotective effects. In this regard, this review summarizes therapeutic targets for AD, PD, and ischemic brain stroke and marine natural products with pharmacological activities on the targets according to taxonomies of marine organisms. Furthermore, several marine natural products on the clinical trials for the treatment of neurological disorders are discussed.

  4. Artificial organs: recent progress in artificial hearing and vision.

    PubMed

    Ifukube, Tohru

    2009-01-01

    Artificial sensory organs are a prosthetic means of sending visual or auditory information to the brain by electrical stimulation of the optic or auditory nerves to assist visually impaired or hearing-impaired people. However, clinical application of artificial sensory organs, except for cochlear implants, is still a trial-and-error process. This is because how and where the information transmitted to the brain is processed is still unknown, and also because changes in brain function (plasticity) remain unknown, even though brain plasticity plays an important role in meaningful interpretation of new sensory stimuli. This article discusses some basic unresolved issues and potential solutions in the development of artificial sensory organs such as cochlear implants, brainstem implants, artificial vision, and artificial retinas.

  5. 20 CFR 404.1525 - Listing of Impairments in appendix 1.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Impairments (the listings) is in appendix 1 of this subpart. It describes for each of the major body systems..., regardless of his or her age, education, or work experience. (b) How is appendix 1 organized? There are two... relationship with their counterparts in part A. (c) How do we use the listings? (1) Each body system section in...

  6. Renal toxicity of anticancer agents targeting HER2 and EGFR.

    PubMed

    Cosmai, Laura; Gallieni, Maurizio; Porta, Camillo

    2015-12-01

    EGFR and HER2 are found overexpressed and/or activated in many different human malignancies (e.g. breast and colon cancer), and a number of drugs specifically targeting these two tyrosine kinases have been developed over the years as anticancer agents. In the present review, the renal safety profile of presently available agents targeting either HER2 or EGFR will be discussed, together with the peculiarities related to their clinical use in patients with impaired renal function, or even in dialysis. Indeed, even though renal toxicity is not so common with these agents, it may nevertheless happen, especially when these agents are combined with traditional chemotherapeutic agents. As a whole, kidney impairment or dialysis should not be regarded per se as reasons not to administer or to stop an active anti-HER or anti-EGFR anticancer treatment, especially given the possibility of significantly improving the life expectancy of many cancer patients with the use of these agents.

  7. A CAI System for Visually Impaired Children to Improve Abilities of Orientation and Mobility

    NASA Astrophysics Data System (ADS)

    Yoneda, Takahiro; Kudo, Hiroaki; Minagawa, Hiroki; Ohnishi, Noboru; Matsubara, Shizuya

    Some visually impaired children have difficulty in simple locomotion, and need orientation and mobility training. We developed a computer assisted instruction system which assists this training. A user realizes a task given by a tactile map and synthesized speech. The user walks around a room according to the task. The system gives the gap of walk path from its target path via both auditory and tactile feedback after the end of a task. Then the user can understand how well the user walked. We describe the detail of the proposed system and task, and the experimental result with three visually impaired children.

  8. Dystypia: isolated typing impairment without aphasia, apraxia or visuospatial impairment.

    PubMed

    Otsuki, Mika; Soma, Yoshiaki; Arihiro, Shoji; Watanabe, Yoshimasa; Moriwaki, Hiroshi; Naritomi, Hiroaki

    2002-01-01

    We report a 60-year-old right-handed Japanese man who showed an isolated persistent typing impairment without aphasia, agraphia, apraxia or any other neuropsychological deficit. We coined the term 'dystypia' for this peculiar neuropsychological manifestation. The symptom was caused by an infarction in the left frontal lobe involving the foot of the second frontal convolution and the frontal operculum. The patient's typing impairment was not attributable to a disturbance of the linguistic process, since he had no aphasia or agraphia. The impairment was not attributable to the impairment of the motor execution process either, since he had no apraxia. Thus, his typing impairment was deduced to be based on a disturbance of the intermediate process where the linguistic phonological information is converted into the corresponding performance. We hypothesized that there is a specific process for typing which branches from the motor programming process presented in neurolinguistic models. The foot of the left second frontal convolution and the operculum may play an important role in the manifestation of 'dystypia'. Copyright 2002 S. Karger AG, Basel

  9. Trajectories of Nutritional Status and Cognitive Impairment among Older Taiwanese with Hip Fracture.

    PubMed

    Wang, H P; Liang, J; Kuo, L M; Chen, C Y; Shyu, Y I L

    2017-01-01

    This paper describes the trajectories of nutritional status and cognitive impairment and their correlation among older Taiwanese over 1 year after hip-fracture surgery. Secondary analysis of data from a clinical trial evaluating the effects of three types of post-discharge care for 292 older hip-fracture patients (age >60 years). Nutritional status was assessed by the Mini Nutritional Assessment before and 1, 3, 6, 12 months after hospital discharge. Cognitive function was measured by the Mini-Mental State Examination before surgery, at hospital discharge, 6 and 12 months after discharge. Trajectories of nutritional status and cognitive impairment were depicted by latent class growth modeling, whereas linkages between nutritional-status and cognitive-impairment trajectories were assessed by multinomial logistic regression. Nutritional status in general improved significantly, particularly during the first 3 months after discharge. We identified three trajectories of nutritional status: malnourished (15.4%), at risk for malnutrition (38.9%), and well-nourished (45.7%). In contrast, cognitive changes followed four largely linear but distinct trajectories: moderately impaired (12.2%), mildly impaired (27.8%), borderline impaired (21.8%), and cognitively intact (38.2%). Trajectories of nutritional status were significantly associated with cognitive-function trajectories. For instance, relative to malnourished patients, well-nourished patients were 95% less likely (OR=0.05, CI =0.01-0.24) to be moderately cognitively impaired. A good nutritional-status trajectory after hip fracture was associated with better cognitive function. To treat and care for elderly hip-fractured patients, specific interventions need to target those who are malnourished or at risk of malnutrition to decrease their risk for cognitive impairment.

  10. Evaluation of the biological activity of the molluscicidal fraction of Solanum sisymbriifolium against non target organisms.

    PubMed

    Bagalwa, Jean-Jacques M; Voutquenne-Nazabadioko, Laurence; Sayagh, Charlotte; Bashwira, Augustin S

    2010-10-01

    The evaluation of the biocidal activity of the fruit of Solanum sisymbriifolium involving non target organisms such as aquatic insects, fish and snails lead to the isolation of the steroidal alkaloids, solamargine and β-solamarine, from the active fractions. The fractions A3 and C, with biological activity against fish, snail and aquatic insect and larvae, are able to affect the good functioning of ecosystem found on alimentary chain. The fraction B seems to be less toxic to fish and aquatic insect and larvae. The fraction B could thus be used as molluscicide in the future. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Spatial short-term memory in children with nonverbal learning disabilities: impairment in encoding spatial configuration.

    PubMed

    Narimoto, Tadamasa; Matsuura, Naomi; Takezawa, Tomohiro; Mitsuhashi, Yoshinori; Hiratani, Michio

    2013-01-01

    The authors investigated whether impaired spatial short-term memory exhibited by children with nonverbal learning disabilities is due to a problem in the encoding process. Children with or without nonverbal learning disabilities performed a simple spatial test that required them to remember 3, 5, or 7 spatial items presented simultaneously in random positions (i.e., spatial configuration) and to decide if a target item was changed or all items including the target were in the same position. The results showed that, even when the spatial positions in the encoding and probe phases were similar, the mean proportion correct of children with nonverbal learning disabilities was 0.58 while that of children without nonverbal learning disabilities was 0.84. The authors argue with the results that children with nonverbal learning disabilities have difficulty encoding relational information between spatial items, and that this difficulty is responsible for their impaired spatial short-term memory.

  12. Impaired Verb Fluency: A Sign of Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Ostberg, Per; Fernaeus, Sven-Erik; Hellstrom, Ake; Bogdanovic, Nenad; Wahlund, Lars Olof

    2005-01-01

    We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive…

  13. 3 CFR 9065 - Proclamation 9065 of November 29, 2013. National Impaired Driving Prevention Month, 2013

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... of impaired driving, improving screening methods, and ensuring law enforcement has the tools and... and community organizations. Together, we can teach young people, friends, and fellow citizens how to...

  14. Psychiatric comorbidity and psychosocial impairment among patients with vertigo and dizziness.

    PubMed

    Lahmann, Claas; Henningsen, Peter; Brandt, Thomas; Strupp, Michael; Jahn, Klaus; Dieterich, Marianne; Eckhardt-Henn, Annegret; Feuerecker, Regina; Dinkel, Andreas; Schmid, Gabriele

    2015-03-01

    Vertigo and dizziness are often not fully explained by an organic illness, but instead are related to psychiatric disorders. This study aimed to evaluate psychiatric comorbidity and assess psychosocial impairment in a large sample of patients with a wide range of unselected organic and non-organic (ie, medically unexplained) vertigo/dizziness syndromes. This cross-sectional study involved a sample of 547 patients recruited from a specialised interdisciplinary treatment centre for vertigo/dizziness. Diagnostic evaluation included standardised neurological examinations, structured clinical interview for major mental disorders (SCID-I) and self-report questionnaires regarding dizziness, depression, anxiety, somatisation and quality of life. Neurological diagnostic workup revealed organic and non-organic vertigo/dizziness in 80.8% and 19.2% of patients, respectively. In 48.8% of patients, SCID-I led to the diagnosis of a current psychiatric disorder, most frequently anxiety/phobic, somatoform and affective disorders. In the organic vertigo/dizziness group, 42.5% of patients, particularly those with vestibular paroxysmia or vestibular migraine, had a current psychiatric comorbidity. Patients with psychiatric comorbidity reported more vertigo-related handicaps, more depressive, anxiety and somatisation symptoms, and lower psychological quality of life compared with patients without psychiatric comorbidity. Almost half of patients with vertigo/dizziness suffer from a psychiatric comorbidity. These patients show more severe psychosocial impairment compared with patients without psychiatric disorders. The worst combination, in terms of vertigo-related handicaps, is having non-organic vertigo/dizziness and psychiatric comorbidity. This phenomenon should be considered when diagnosing and treating vertigo/dizziness in the early stages of the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  15. Dizziness: relating the severity of vertigo to the degree of handicap by measuring vestibular impairment.

    PubMed

    Pérez, Nicolás; Martin, Eduardo; Garcia-Tapia, Rafael

    2003-03-01

    We sought to correlate the severity of vertigo and handicap in patients with vestibular pathology according to measures of impairment. We conducted a prospective assessment of patients with dizziness by means of caloric, rotatory test, and computerized dynamic posturography to estimate impairment. Handicap and severity of vertigo were determined with specific questionnaires (Dizziness Handicap Inventory and UCLA-DQ). A fair relationship were found between severity of dizziness and vestibular handicap. When impairment was taken into consideration, values were still fair and only moderate for a group of patients with an abnormal caloric test as the only pathologic finding. The composite score from the sensory organization test portion of the computerized dynamic posturography is fairly correlated to severity of vertigo and handicap in the whole population of patients, but no correlation was found when they were assigned to groups of vestibular impairment. To assess vestibular impairment, the results from several tests must be taken into account. However, vestibular handicap is not solely explained with measurements of impairment and/or severity.

  16. Control of Sand Flies with Attractive Toxic Sugar Baits (ATSB) and Potential Impact on Non-Target Organisms in Morocco

    DTIC Science & Technology

    2015-02-08

    dinotefuran has successful con- trolled Culex and Aedes spp. in similar field sites in Morocco [22]. However, this if the first report of the use of...et al. Control of Aedes abopttus with attractive toxic sugar baits (A TSB) and potential Impact on non target organisms In St. Augustine, Florida...of Anopheles sergenti and Aedes CO!Pk.JS populations following presentation of attractive toxic (splnosad) sugar bait stations In an oasis. J Am

  17. Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis?

    PubMed

    Gaberel, Thomas; Gakuba, Clement; Goulay, Romain; Martinez De Lizarrondo, Sara; Hanouz, Jean-Luc; Emery, Evelyne; Touze, Emmanuel; Vivien, Denis; Gauberti, Maxime

    2014-10-01

    The aim of the present study was to investigate the impact of different stroke subtypes on the glymphatic system using MRI. We first improved and characterized an in vivo protocol to measure the perfusion of the glymphatic system using MRI after minimally invasive injection of a gadolinium chelate within the cisterna magna. Then, the integrity of the glymphatic system was evaluated in 4 stroke models in mice including subarachnoid hemorrhage (SAH), intracerebral hemorrhage, carotid ligature, and embolic ischemic stroke. We were able to reliably evaluate the glymphatic system function using MRI. Moreover, we provided evidence that the glymphatic system was severely impaired after SAH and in the acute phase of ischemic stroke, but was not altered after carotid ligature or in case of intracerebral hemorrhage. Notably, this alteration in glymphatic perfusion reduced brain clearance rate of low-molecular-weight compounds. Interestingly, glymphatic perfusion after SAH can be improved by intracerebroventricular injection of tissue-type plasminogen activator. Moreover, spontaneous arterial recanalization was associated with restoration of the glymphatic function after embolic ischemic stroke. SAH and acute ischemic stroke significantly impair the glymphatic system perfusion. In these contexts, injection of tissue-type plasminogen activator either intracerebroventricularly to clear perivascular spaces (for SAH) or intravenously to restore arterial patency (for ischemic stroke) may improve glymphatic function. © 2014 American Heart Association, Inc.

  18. Helping Children with Visual and Motor Impairments Make the Most of Their Visual Abilities.

    ERIC Educational Resources Information Center

    Amerson, Marie J.

    1999-01-01

    Lists strategies for promoting functional vision use in children with visual and motor impairments, including providing postural stability, presenting visual attention tasks when energy level is the highest, using a slanted work surface, placing target items in varied locations within reach, and determining the most effective visual adaptations.…

  19. Eye gaze performance for children with severe physical impairments using gaze-based assistive technology-A longitudinal study.

    PubMed

    Borgestig, Maria; Sandqvist, Jan; Parsons, Richard; Falkmer, Torbjörn; Hemmingsson, Helena

    2016-01-01

    Gaze-based assistive technology (gaze-based AT) has the potential to provide children affected by severe physical impairments with opportunities for communication and activities. This study aimed to examine changes in eye gaze performance over time (time on task and accuracy) in children with severe physical impairments, without speaking ability, using gaze-based AT. A longitudinal study with a before and after design was conducted on 10 children (aged 1-15 years) with severe physical impairments, who were beginners to gaze-based AT at baseline. Thereafter, all children used the gaze-based AT in daily activities over the course of the study. Compass computer software was used to measure time on task and accuracy with eye selection of targets on screen, and tests were performed with the children at baseline, after 5 months, 9-11 months, and after 15-20 months. Findings showed that the children improved in time on task after 5 months and became more accurate in selecting targets after 15-20 months. This study indicates that these children with severe physical impairments, who were unable to speak, could improve in eye gaze performance. However, the children needed time to practice on a long-term basis to acquire skills needed to develop fast and accurate eye gaze performance.

  20. Perceptual training yields rapid improvements in visually impaired youth.

    PubMed

    Nyquist, Jeffrey B; Lappin, Joseph S; Zhang, Ruyuan; Tadin, Duje

    2016-11-30

    Visual function demands coordinated responses to information over a wide field of view, involving both central and peripheral vision. Visually impaired individuals often seem to underutilize peripheral vision, even in absence of obvious peripheral deficits. Motivated by perceptual training studies with typically sighted adults, we examined the effectiveness of perceptual training in improving peripheral perception of visually impaired youth. Here, we evaluated the effectiveness of three training regimens: (1) an action video game, (2) a psychophysical task that combined attentional tracking with a spatially and temporally unpredictable motion discrimination task, and (3) a control video game. Training with both the action video game and modified attentional tracking yielded improvements in visual performance. Training effects were generally larger in the far periphery and appear to be stable 12 months after training. These results indicate that peripheral perception might be under-utilized by visually impaired youth and that this underutilization can be improved with only ~8 hours of perceptual training. Moreover, the similarity of improvements following attentional tracking and action video-game training suggest that well-documented effects of action video-game training might be due to the sustained deployment of attention to multiple dynamic targets while concurrently requiring rapid attending and perception of unpredictable events.

  1. Perceptual training yields rapid improvements in visually impaired youth

    PubMed Central

    Nyquist, Jeffrey B.; Lappin, Joseph S.; Zhang, Ruyuan; Tadin, Duje

    2016-01-01

    Visual function demands coordinated responses to information over a wide field of view, involving both central and peripheral vision. Visually impaired individuals often seem to underutilize peripheral vision, even in absence of obvious peripheral deficits. Motivated by perceptual training studies with typically sighted adults, we examined the effectiveness of perceptual training in improving peripheral perception of visually impaired youth. Here, we evaluated the effectiveness of three training regimens: (1) an action video game, (2) a psychophysical task that combined attentional tracking with a spatially and temporally unpredictable motion discrimination task, and (3) a control video game. Training with both the action video game and modified attentional tracking yielded improvements in visual performance. Training effects were generally larger in the far periphery and appear to be stable 12 months after training. These results indicate that peripheral perception might be under-utilized by visually impaired youth and that this underutilization can be improved with only ~8 hours of perceptual training. Moreover, the similarity of improvements following attentional tracking and action video-game training suggest that well-documented effects of action video-game training might be due to the sustained deployment of attention to multiple dynamic targets while concurrently requiring rapid attending and perception of unpredictable events. PMID:27901026

  2. Development of a total maximum daily load (TMDL) for acid-impaired lakes in the Adirondack region of New York

    NASA Astrophysics Data System (ADS)

    Fakhraei, Habibollah; Driscoll, Charles T.; Selvendiran, Pranesh; DePinto, Joseph V.; Bloomfield, Jay; Quinn, Scott; Rowell, H. Chandler

    2014-10-01

    Acidic deposition has impaired acid-sensitive surface waters in the Adirondack region of New York by decreasing pH and acid neutralizing capacity (ANC). In spite of air quality programs over past decades, 128 lakes in the Adirondacks were classified as “impaired” under Section 303(d) of the Clean Water Act in 2010 due to elevated acidity. The biogeochemical model, PnET-BGC, was used to relate decreases in atmospheric sulfur (S) and nitrogen (N) deposition to changes in lake water chemistry. The model was calibrated and confirmed using observed soil and lake water chemistry data and then was applied to calculate the maximum atmospheric deposition that the impaired lakes can receive while still achieving ANC targets. Two targets of ANC were used to characterize the recovery of acid-impaired lakes: 11 and 20 μeq L-1. Of the 128 acid-impaired lakes, 97 currently have ANC values below the target value of 20 μeq L-1 and 83 are below 11 μeq L-1. This study indicates that a moderate control scenario (i.e., 60% decrease from the current atmospheric S load) is projected to recover the ANC of lakes at a mean rate of 0.18 and 0.05 μeq L-1 yr-1 during the periods 2022-2050 and 2050-2200, respectively. The total maximum daily load (TMDL) of acidity corresponding to this moderate control scenario was estimated to be 7.9 meq S m-2 yr-1 which includes a 10% margin of safety.

  3. Articulation generalization of voiced-voiceless sounds in hearing-impaired children.

    PubMed

    McReynolds, L V; Jetzke, E

    1986-11-01

    Eight hearing-impaired children participated in a study exploring the effect of training (+) or (-) voicing on generalization to cognates. In an experimental multiple baseline study across behaviors, children were trained on pairs of voiced and voiceless target sounds that they had previously omitted in final position. The pairs consisted of the /t/ and /g/ and the /d/ and /k/. When /t/ was trained, generalization was tested to (a) untrained words with the /t/ in the final position and (b) untrained words containing /d/ (the cognate) of the /t/. In like manner, when /d/ was trained, generalization was tested to both the /d/ and /t/ words. The /g/ and /k/ received identical treatment. A contrast procedure was used to teach the children to produce the final consonants. When training criterion was reached, generalization was tested. Results showed that 6 of the 8 children generalized both the voiced and unvoiced target sounds to 50% or more of the target sound probe items. Results also indicated that more generalization occurred to the voiceless cognate from voiced target sound training than occurred to voiced cognates from voiceless target sound training.

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

    PubMed

    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.

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

    PubMed

    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 <130/<80 mm Hg. 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 (<55 years), the mutually independent effect sizes associated with 1 SD increases in 24-hour systolic/diastolic 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 (P<0.001/0.54) for pulse wave velocity. In older participants, these estimates were +3.58/+0.30 g/m(2) (P=0.045/0.88), +1.23/+1.05 mg/mmol (P=0.002/0.54), and +0.76/-0.49 m/s (P<0.001/<0.001), respectively. In conclusion, 24-hour systolic blood 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.

  6. Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ni, Cheng; Li, Zhengqian; Qian, Min

    Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased andmore » peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.« less

  7. Impact of Pediatric Vision Impairment on Daily Life: Results of Focus Groups

    PubMed Central

    DeCarlo, Dawn K.; McGwin, Gerald; Bixler, Martha L.; Wallander, Jan; Owsley, Cynthia

    2012-01-01

    Purpose To identify through focus groups of visually impaired children and their parents, relevant content for a vision-targeted health-related quality of life questionnaire designed for children ages 6-12. Methods Six focus groups of children with vision impairment ages 6 -12 and six focus groups of their parents were conducted by trained facilitators using a guided script. Sessions were recorded, transcribed and coded per a standardized protocol for content analysis. Comments were placed in thematic categories and each coded as positive, negative or neutral. Results Twenty-four children (mean age 9.4 years) with vision impairment from a variety of causes and 23 parents participated. The child focus groups generated 1,163 comments, of which 52% (n=599) were negative, 12% (n=138) were neutral and 37% (n=426) were positive. The three most common topical areas among children were: glasses and adaptive equipment (18%), psychosocial (14%) and school (14%). The parent focus groups generated 1,952 comments of which 46% (n=895) were negative, 16% (n=323) were neutral and 38% (n=734) were positive. The three most common topical areas among parents were: school (21%), expectations or frustrations (14%) and psychosocial (13%). Conclusions Pediatric vision impairment has significant effects on health related quality of life, as reported by children with vision impairment and their parents in their own words. These findings will provide the content to guide construction of a survey instrument to assess vision-specific, health-related quality of life in children with vision impairment. PMID:22863790

  8. Insomnia in shift work disorder relates to occupational and neurophysiological impairment.

    PubMed

    Belcher, Ren; Gumenyuk, Valentina; Roth, Thomas

    2015-04-15

    To determine whether occupational and neurophysiological decrements within shift work disorder (SWD) are differentially related to its two diagnostic symptoms, insomnia and excessive sleepiness. Thirty-four permanent night workers participated in an overnight lab protocol including a multiple sleep latency test (MSLT) and an event-related brain potential (ERP) task testing auditory target detection (P3a and P3b). At 16:00, each subject completed an Endicott Work Productivity Scale (EWPS), two Insomnia Severity Indices (ISI-Day, ISI-Night), and an Epworth Sleepiness Scale (ESS). Subjects were grouped by ISI and ESS scores into clinical phenotypes. This study compared EWPS and ERP results between alert insomniacs ("AI," reporting insomnia without sleepiness), sleepy insomniacs ("SI," reporting both insomnia and sleepiness), and controls. The AI group was most impaired on the EWPS, significantly more impaired than controls (25.8 ± 14.8 vs. 12.3 ± 9.4, p < 0.05). SI were not statistically different from controls (19.5 ± 8.7 vs. 12.3 ± 9.4, p > 0.05). Compared to controls, AI showed significantly attenuated P3a response (Fcz, Czp, Cpz, mean difference [MD] 1.62-1.77, p < 0.05) and target-detection P3b response (Fcz, Czp, Cpz, MD 1.28-1.64, p < 0.05). P3b in SI was not different from controls (p > 0.10), and P3a was only different at one electrode site (Cpz, MD 1.43, p < 0.01). Neither the MSLT nor the ESS correlated with EWPS scores or ERP (P3a/P3b) amplitudes (p > 0.10). However, the mean of the ISI measurements correlated with the EWPS (r = 0.409, p < 0.01) and the attention-to-novelty P3a (r = -0.410, p < 0.01). Among shift work disorder patients, insomnia is linked to functional and cognitive impairments. Insomniacs with normal sleepiness showed more severe impairments than insomniacs who also reported excessive sleepiness. © 2015 American Academy of Sleep Medicine.

  9. The relationship between impaired driving crashes and beliefs about impaired driving: do residents in high crash rate counties have greater concerns about impaired driving?

    PubMed

    Beck, Kenneth H; Yan, Alice F; Wang, Min Qi; Kerns, Timothy J; Burch, Cynthia A

    2009-04-01

    The purpose of this investigation was to examine the relationship between impaired driving crashes and public beliefs and concerns about impaired driving across each of Maryland's twenty-four counties (including Baltimore City). It was hypothesized that residents of counties that experience higher impaired driving crashes would express more concerns about impaired driving and perceive more risks about driving impaired than residents of counties that have lower rates of impaired driving. Data for alcohol impaired driving crashes were obtained for the years 2004-2006. These data were compared to public opinion data that was obtained annually by random-digit-dial telephone surveys from 2004 to 2007. Concerns about drunk driving as well as perceptions of the likelihood of being stopped by the police if one were to drive after having too much to drink were related to counties with higher serious impaired driving crash rates, as were perceptions that the police and the legal system were too lenient. Perceptions about the likelihood of being stopped by the police were higher in those counties with more impaired driving enforcement activity. Perceptions of concern appear to be shaped more by crash exposure than enforcement activity. Campaigns that address impaired driving prevention should substantially increase enforcement, strengthen the adjudication process of impaired drivers, and emphasize the potential seriousness of drinking-driving crashes in their promotional activities.

  10. [Employed with a hearing impairment in Saxony, Saxony-Anhalt, and Thuringia : Regional results of the GINKO study].

    PubMed

    Weber, A; Weber, U

    2016-10-01

    Hearing impairments and hearing loss cause deficits in communication ability and represent relevant participation restrictions according to the International Classification of Functioning, Disability and Health (ICF). In order to counteract these participation restrictions, particularly in the workplace, several acts have been passed in Germany including SGB IX and UN-BRK. The implementation of these laws in the federal states Saxony, Saxony-Anhalt, and Thuringia is presented from the perspective of hearing-impaired employees. In the GINKO study, conducted in cooperation with self-help organizations, a standardized written questionnaire with items about the workplace was administered to employed persons with hearing impairments. The questionnaire was also available online with sign language. Overall, 3189 severely disabled hearing-impaired working persons responded to the GINKO survey, of whom n = 260 (8.3 %) were from Saxony, n = 53 (1.7 %) from Saxony-Anhalt, and n = 62 (1.9 %) from Thuringia. The majority of participants reported that they did not (yet) have an accessible workplace and that assistive services were not available to all hearing-impaired employees. This was true overall and in the three individual states. There are still considerable deficits in the implementation of legally required possibilities. No statistically significant differences exist between the three federal states in terms of utilization of legally required assistive services in the workplace or the accessibility of the workplace to hearing-impaired employees. Causes for this might be found in insufficient information regarding legal possibilities available to hearing-impaired employees. Therefore, information about state-wide self-help organizations is important to encourage participation in working life in accordance with ICF after successful medical treatment.

  11. The prevalence and causes of visual impairment in seven-year-old children.

    PubMed

    Ghaderi, Soraya; Hashemi, Hassan; Jafarzadehpur, Ebrahim; Yekta, Abbasali; Ostadimoghaddam, Hadi; Mirzajani, Ali; Khabazkhoob, Mehdi

    2018-05-01

    To report the prevalence and causes of visual impairment in seven-year-old children in Iran and its relationship with socio-economic conditions. In a cross-sectional population-based study, first-grade students in the primary schools of eight cities in the country were randomly selected from different geographic locations using multistage cluster sampling. The examinations included visual acuity measurement, ocular motility evaluation, and cycloplegic and non-cycloplegic refraction. Using the definitions of the World Health Organization (presenting visual acuity less than or equal to 6/18 in the better eye) to estimate the prevalence of vision impairment, the present study reported presenting visual impairment in seven-year-old children. Of 4,614 selected students, 4,106 students participated in the study (response rate 89 per cent), of whom 2,127 (51.8 per cent) were male. The prevalence of visual impairment according to a visual acuity of 6/18 was 0.341 per cent (95 per cent confidence interval 0.187-0.571); 1.34 per cent (95 per cent confidence interval 1.011-1.74) of children had visual impairment according to a visual acuity of 6/18 in at least one eye. Sixty-six (1.6 per cent) and 23 (0.24 per cent) children had visual impairment according to a visual acuity of 6/12 in the worse and better eye, respectively. The most common causes of visual impairment were refractive errors (81.8 per cent) and amblyopia (14.5 per cent). Among different types of refractive errors, astigmatism was the main refractive error leading to visual impairment. According to the concentration index, the distribution of visual impairment in children from low-income families was higher. This study revealed a high prevalence of visual impairment in a representative sample of seven-year-old Iranian children. Astigmatism and amblyopia were the most common causes of visual impairment. The distribution of visual impairment was higher in children from low-income families. Cost

  12. The effects of impairments on employment and wages: estimates from the 1984 and 1990 SIPP.

    PubMed

    Baldwin, M L

    1999-01-01

    Unlike the minority groups covered by civil rights laws in the past, the disabled population is a heterogeneous group. Because of differences in the nature and onset of health conditions, it is important to study the labor market experiences of different impairment groups separately, rather than treating "disabled workers" as a single group. This article uses data from the 1984 and the 1990 panels of the Survey of Income and Program Participation to analyze trends in the employment and wages of six impairment groups in the years immediately preceding the ADA. The results confirm the diversity of labor market experiences within the disabled population and suggest that policies designed to improve labor market outcomes for workers with disabilities in response to the ADA should be targeted to the different needs of different impairment groups.

  13. Target and non-target toxicity of fern extracts against mosquito vectors and beneficial aquatic organisms.

    PubMed

    Kamaraj, Chinnaperumal; Deepak, Paramasivam; Balasubramani, Govindasamy; Karthi, Sengodan; Arul, Dhayalan; Aiswarya, Dilipkumar; Amutha, Vadivel; Vimalkumar, Elangovan; Mathivanan, Damodaran; Suseem, Sundaram Renjitham; Muthu-Pandian, Chanthini Kanagaraj; Senthil-Nathan, Sengottayan; Perumal, Pachiappan

    2018-06-06

    Dengue and malaria are significant mosquito-borne diseases that are rapidly spread worldwide, mainly in temperate countries. Pteridophytes were identified to be a significant source of novel mosquitocidal agents. The present research was to explore the eco-friendly larvicides from methanol extracts of ferns, viz., Actiniopteris radiata, Adiantum caudatum, Cheilanthes swartzii, Hemionitis arifolia and Lycopodium clavatum. The larvicidal potential of the extracts screened using larvae of dengue vector Aedes aegypti (III and IV instar) and malarial vector Anopheles stephensi (III and IV instar), showed 10-100% mortality rates. Biosafety assessment was made on embryos of Danio rerio and Artemia nauplii. The phyto-constituents of the methanol extract of A. radiata leaves were identified through gas chromatography-mass spectrometry (GC-MS). Methanolic leaf extracts of A. radiata, A. caudatum and C. swartzii exhibited larvicidal activity against III and IV instar larvae of Ae. aegypti (LC 50 : 37.47, 74.51 and 152.38 and 67.58, 95.89 and 271.46 ppm) and An. stephensi (LC 50 : 70.35, 112.12 and 301.05 and 113.83, 175.30 and 315.19 ppm), respectively. The GC-MS of the methanol extract of A. radiata leaves revealed the presence of 7 phyto-components among which, Carbamic acid, phenyl-, (2-Nitrophenyl) methyl ester (1), Benzoic acid, 3- methylbenzoate (2) and 4-(benzylimino)- 1,4-dihydro-1-(p-toluoylmethyl) pyridine (3) were dominant. Biosafety assessment of methanol extract of A. radiata leaves on embryos of Danio rerio (Zebra fish) and Artemia nauplii (micro crustacean) revealed that there were no destructive or teratogenic effects. To conclude, the larvicidal activity and insignificant toxicity to non-target aquatic organisms of A. radiata leaves makes it a potential and environment safe biocontrol agent against dengue and malarial vectors. Copyright © 2018. Published by Elsevier Inc.

  14. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s). An...

  15. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s). An...

  16. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s). An...

  17. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s). An...

  18. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s). An...

  19. REM Sleep Behavior Disorder and Cognitive Impairment in Parkinson's Disease.

    PubMed

    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.

  20. Antigen-Specific Immune Modulation Targets mTORC1 Function To Drive Chemokine Receptor-Mediated T Cell Tolerance.

    PubMed

    Chen, Weirong; Wan, Xiaoxiao; Ukah, Tobechukwu K; Miller, Mindy M; Barik, Subhasis; Cattin-Roy, Alexis N; Zaghouani, Habib

    2016-11-01

    To contain autoimmunity, pathogenic T cells must be eliminated or diverted from reaching the target organ. Recently, we defined a novel form of T cell tolerance whereby treatment with Ag downregulates expression of the chemokine receptor CXCR3 and prevents diabetogenic Th1 cells from reaching the pancreas, leading to suppression of type 1 diabetes (T1D). This report defines the signaling events underlying Ag-induced chemokine receptor-mediated tolerance. Specifically, we show that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells. Indeed, Ag administration induces upregulation of programmed death-ligand 1 on dendritic cells in a T cell-dependent manner. In return, programmed death-ligand 1 interacts with the constitutively expressed programmed death-1 on the target T cells and stimulates docking of Src homology 2 domain-containing tyrosine phosphatase 2 phosphatase to the cytoplasmic tail of programmed death-1. Active Src homology 2 domain-containing tyrosine phosphatase 2 impairs the signaling function of the PI3K/protein kinase B (AKT) pathway, leading to functional defect of mTORC1, downregulation of CXCR3 expression, and suppression of T1D. Thus, mTORC1 component of the metabolic pathway serves as a target for chemokine receptor-mediated T cell tolerance and suppression of T1D. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Mild Cognitive Impairment: Diagnosis, Longitudinal Course, and Emerging Treatments

    PubMed Central

    Vega, Jennifer N.; Newhouse, Paul A.

    2014-01-01

    Mild cognitive impairment (MCI) is widely regarded as the intermediate stage of cognitive impairment between the changes seen in normal cognitive aging and those associated with dementia. Elderly patients with MCI constitute a high-risk population for developing dementia, in particular Alzheimer’s disease (AD). Although the core clinical criteria for MCI have remained largely unchanged, the operational definition of MCI has undergone several revisions over the course of the last decade and remains an evolving diagnosis. Prognostic implications of this diagnosis are becoming clearer with regard to the risk of progressive cognitive deterioration. Although patients with MCI may represent an optimal target population for pharmacological and non-pharmacological interventions, results from clinical trials have been mixed and a definitive effective treatment remains elusive. This article provides a brief overview of the evolution of the concept of MCI and reviews current diagnostic criteria, the longitudinal course of the disorder, and current and emerging treatments for MCI. PMID:25160795

  2. Mild cognitive impairment affects motor control and skill learning.

    PubMed

    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. Temporal organization as a therapeutic target

    PubMed Central

    Wirz-Justice, Anna

    2012-01-01

    Biological functions occur at many different frequencies, and each has its healthy and pathological ranges, patterns, and properties. Physiology, biochemistry, and behavior are not only organized at the morphological level in cells and organs, but separated or coordinated in time for minimal interference and optimal function. One of the most important temporal frameworks is that of the 24-hour day-night cycle, and its change in day length with season. Robust circadian rhythms are important for mental and physical well-being. Though rhythms have been long neglected as irrelevant (in spite of the high prevalence of sleep disorders in nearly every psychiatric illness), we now have tools to document rhythm disruption and, through better understanding of underlying molecular and physiological mechanisms, to develop therapeutic applications. Light as the major synchronizing agent of the biological clock is becoming a treatment option not only for winter depression but other, nonseasonal forms, as well as an adjunct in optimizing sleep-wake cycles, daytime alertness, cognition, and mood in many neuropsychiatric illnesses. Melatonin is the signal of darkness and promotes sleep onset. Manipulation of sleep (wake therapy, phase advance) has yielded the most rapid, nonpharmacological antidepressant effect known, and combinations (with light, medication) provide long-lasting response. Thus, by analogy, new molecules to augment synchronization or mimic changes occuring during night-time wakefulness may yield novel treatments. This issue on biological rhythms contains articles on a variety of different frequencies not included in the usual definition of chronobiology, but which open up interesting approaches to time and illness. PMID:23393412

  4. Physical Education Lessons and Activity Status of Visually Impaired and Sighted Adolescents.

    PubMed

    Demirturk, Funda; Kaya, Mustafa

    2015-11-15

    BACKGROUND This study investigated participation in physical education and sports lessons of visually impaired adolescents and their sighted peers and compared their physical activity levels. MATERIAL AND METHODS A total of 22 visually impaired children of mean age 13.59±1.14 years and 31 sighted children aged 13.61±0.50 years participated in the study. A questionnaire prepared for this study was used to investigate participation of visually impaired adolescents and their sighted peers in physical education and sports lessons at school and the problems they encounter while doing sports. The Turkish version of the International Physical Activity Questionnaire - short-form (IPAQ-SF) was used to evaluate the physical activity level of the subjects. RESULTS The results of our study suggest that physical activity levels of visually impaired children and their sighted children were similar (p>0.05). Totally blind children had lower IPAQ scores than those with low vision (p<0.05), and girls were less active physically than boys (p<0.05). There were few differences in physical education lessons of the groups, in taking part in sports-related organizations, and future plans. CONCLUSIONS Children in secondary school, especially visually impaired children, need to be more motivated and more encouraged to take part in various sports or physical activities.

  5. Organ donor screening practices for Strongyloides stercoralis infection among US organ procurement organizations.

    PubMed

    Abanyie, Francisca A; Valice, Emily; Delli Carpini, Kristin W; Gray, Elizabeth B; McAuliffe, Isabel; Chin-Hong, Peter V; Handali, Sukwan; Montgomery, Susan P; Huprikar, Shirish

    2018-03-07

    Targeted donor screening for strongyloidiasis performed at the time of organ procurement can prevent this life-threatening donor-derived infection. The Association of Organ Procurement Organizations surveyed members to determine the number of US organ procurement organizations (OPOs) performing donor screening for Strongyloides infection and their screening practices. All 58 OPOs responded to the survey. Only 6 (10%) currently screen donors for strongyloidiasis; most OPOs started 6-36 months before the survey and one started 6 years prior. All used risk-based criteria to determine which donors to screen, though the criteria varied among OPOs. A median of 56 donors have been screened at each OPO since initiating their screening programs, with a median of 2 infected donors (range 0-13) identified. Overall, 53 organs have been transplanted from 22 infected donors, including hearts, lungs, kidneys, and livers. Of 52 OPOs not currently screening, 20 had considered screening and one plans to start screening in the near future. Of those considering risk-based screening, most had not decided on the criteria. Uncertainty about the benefits of and guidelines for screening and misconceptions about the interpretation of test results were concerns shared by non-screening OPOs. Continued education and advocacy on the importance of targeted donor screening are needed. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

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

    PubMed

    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.

  7. The combined effect of visual impairment and cognitive impairment on disability in older people.

    PubMed

    Whitson, Heather E; Cousins, Scott W; Burchett, Bruce M; Hybels, Celia F; Pieper, Carl F; Cohen, Harvey J

    2007-06-01

    To determine the risk of disability in individuals with coexisting visual and cognitive impairment and to compare the magnitude of risk associated with visual impairment, cognitive impairment, or the multimorbidity. Prospective cohort. North Carolina. Three thousand eight hundred seventy-eight participants in the North Carolina Established Populations for the Epidemiologic Studies of the Elderly with nonmissing visual status, cognitive status, and disability status data at baseline Short Portable Mental Status Questionnaire (cognitive impairment defined as > or =4 errors), self reported visual acuity (visual impairment defined as inability to see well enough to recognize a friend across the street or to read newspaper print), demographic and health-related variables, disability status (activities of daily living (ADLs), instrumental activities of daily living (IADLs), mobility), death, and time to nursing home placement. Participants with coexisting visual and cognitive impairment were at greater risk of IADL disability (odds ratio (OR)=6.50, 95% confidence interval (CI)=4.34-9.75), mobility disability (OR=4.04, 95% CI=2.49-6.54), ADL disability (OR=2.84, 95% CI=1.87-4.32), and incident ADL disability (OR=3.66, 95%, CI=2.36-5.65). In each case, the estimated OR associated with the multimorbidity was greater than the estimated OR associated with visual or cognitive impairment alone, a pattern that was not observed for other adverse outcomes assessed. No significant interactions were observed between cognitive impairment and visual impairment as predictors of disability status. Individuals with coexisting visual impairment and cognitive impairment are at high risk of disability, with each condition contributing additively to disability risk. Further study is needed to improve functional trajectories in patients with this prevalent multimorbidity. When visual or cognitive impairment is present, efforts to maximize the other function may be beneficial.

  8. Extent and neural basis of semantic memory impairment in mild cognitive impairment.

    PubMed

    Barbeau, Emmanuel J; Didic, Mira; Joubert, Sven; Guedj, Eric; Koric, Lejla; Felician, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick; Ceccaldi, Mathieu

    2012-01-01

    An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.

  9. High mobility high efficiency organic films based on pure organic materials

    DOEpatents

    Salzman, Rhonda F [Ann Arbor, MI; Forrest, Stephen R [Ann Arbor, MI

    2009-01-27

    A method of purifying small molecule organic material, performed as a series of operations beginning with a first sample of the organic small molecule material. The first step is to purify the organic small molecule material by thermal gradient sublimation. The second step is to test the purity of at least one sample from the purified organic small molecule material by spectroscopy. The third step is to repeat the first through third steps on the purified small molecule material if the spectroscopic testing reveals any peaks exceeding a threshold percentage of a magnitude of a characteristic peak of a target organic small molecule. The steps are performed at least twice. The threshold percentage is at most 10%. Preferably the threshold percentage is 5% and more preferably 2%. The threshold percentage may be selected based on the spectra of past samples that achieved target performance characteristics in finished devices.

  10. Multiple Learning Strategies Project. Building Maintenance & Engineering. Educable Mentally Impaired. [Vol. 3.

    ERIC Educational Resources Information Center

    Steinberg, Alan; And Others

    This instructional package is one of three designed for educable mentally impaired students in the vocational area of building maintenance and engineering. The thirty-one learning modules are organized into nine units: grounds; sanitation; boiler maintenance and operation; power and hand tools; cabinet construction; repair of damaged furniture;…

  11. Gender differences and demographic influences in perceived concern for driver safety and support for impaired driving countermeasures.

    PubMed

    Butters, Jennifer; Mann, Robert E; Wickens, Christine M; Boase, Paul

    2012-12-01

    Driving safety, impaired driving, and legislation to address these concerns remain important issues. It is imperative countermeasures be targeted toward the most appropriate groups. This paper explores the potential relationship between gender and driving attitudes toward safety issues and impaired-driving countermeasures. The data are from the 2007 Impaired Driving Survey commissioned by Transport Canada and Mothers Against Drunk Driving (MADD) Canada. The survey is a, stratified by region, telephone survey of 1,514 Canadian drivers 18years of age and older with a valid driver's license who had driven within the past 30days. The findings illustrate a consistent impact of gender on these issues. Other variables were also identified as relevant factors although less consistently. Current findings suggest that strategies for building support for interventions, or for changing risk perception/concern for risky driving behaviors should be tailored by gender to maximize the potential for behavior change. This information may assist program and policy developers through the identification of more or less receptive target groups. Future research directions are also presented. Copyright © 2012 National Safety Council and Elsevier Ltd. All rights reserved.

  12. Open-target sparse sensing of biological agents using DNA microarray

    PubMed Central

    2011-01-01

    Background Current biosensors are designed to target and react to specific nucleic acid sequences or structural epitopes. These 'target-specific' platforms require creation of new physical capture reagents when new organisms are targeted. An 'open-target' approach to DNA microarray biosensing is proposed and substantiated using laboratory generated data. The microarray consisted of 12,900 25 bp oligonucleotide capture probes derived from a statistical model trained on randomly selected genomic segments of pathogenic prokaryotic organisms. Open-target detection of organisms was accomplished using a reference library of hybridization patterns for three test organisms whose DNA sequences were not included in the design of the microarray probes. Results A multivariate mathematical model based on the partial least squares regression (PLSR) was developed to detect the presence of three test organisms in mixed samples. When all 12,900 probes were used, the model correctly detected the signature of three test organisms in all mixed samples (mean(R2)) = 0.76, CI = 0.95), with a 6% false positive rate. A sampling algorithm was then developed to sparsely sample the probe space for a minimal number of probes required to capture the hybridization imprints of the test organisms. The PLSR detection model was capable of correctly identifying the presence of the three test organisms in all mixed samples using only 47 probes (mean(R2)) = 0.77, CI = 0.95) with nearly 100% specificity. Conclusions We conceived an 'open-target' approach to biosensing, and hypothesized that a relatively small, non-specifically designed, DNA microarray is capable of identifying the presence of multiple organisms in mixed samples. Coupled with a mathematical model applied to laboratory generated data, and sparse sampling of capture probes, the prototype microarray platform was able to capture the signature of each organism in all mixed samples with high sensitivity and specificity. It was demonstrated

  13. Effects of carvedilol or amlodipine on target organ damage in L-NAME hypertensive rats: their relationship with blood pressure variability.

    PubMed

    Del Mauro, Julieta S; Prince, Paula D; Donato, Martín; Fernandez Machulsky, Nahuel; Morettón, Marcela A; González, Germán E; Bertera, Facundo M; Carranza, Andrea; Gorzalczany, Susana B; Chiappetta, Diego A; Berg, Gabriela; Morales, Celina; Gelpi, Ricardo J; Taira, Carlos A; Höcht, Christian

    2017-04-01

    The aim of the study was to compare the effects of chronic oral treatment with carvedilol or amlodipine on blood pressure, blood pressure variability and target organ damage in N-nitro-l-arginine methyl ester (L-NAME) hypertensive rats. Wistar rats were treated with L-NAME administered in the drinking water for 8 weeks together with oral administration of carvedilol 30 mg/kg (n = 6), amlodipine 10 mg/kg (n = 6), or vehicle (n = 6). At the end of the treatment, echocardiographic evaluation, blood pressure, and short-term variability measurements were performed. Left ventricular and thoracic aortas were removed to assess activity of metalloproteinase 2 and 9 and expression levels of transforming growth factor β, tumor necrosis factor α, and interleukin 6. Histological samples were prepared from both tissues. Carvedilol and amlodipine induced a comparable reduction of systolic and mean arterial pressure and its short-term variability in L-NAME rats. The expression of transforming growth factor β, tumor necrosis factor α, and interleukin 6 decreased in both organs after carvedilol or amlodipine treatment and the activity of metalloproteinase was reduced in aortic tissue. Treatment with carvedilol or amlodipine completely prevented left ventricular collagen deposition and morphometric alterations in aorta. Oral chronic treatment with carvedilol or amlodipine significantly attenuates blood pressure variability and reduces target organ damage and biomarkers of tissue fibrosis and inflammation in L-NAME hypertensive rats. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  14. The Impaired Social Worker.

    ERIC Educational Resources Information Center

    Reamer, Frederic G.

    1992-01-01

    Discusses concept of the impaired professional; reviews research on various types of impairment (personality disorders, depression and other emotional problems, marital problems, and physical illness), prevalence and causes of impairment, and responses to it; and outlines model assessment and action plan for social workers who encounter an…

  15. The global burden of disabling hearing impairment: a call to action

    PubMed Central

    Neumann, Katrin J; Saunders, James E

    2014-01-01

    Abstract At any age, disabling hearing impairment has a profound impact on interpersonal communication, psychosocial well-being, quality of life and economic independence. According to the World Health Organization’s estimates, the number of people with such impairment increased from 42 million in 1985 to about 360 million in 2011. This last figure includes 7.5 million children less than 5 years of age. In 1995, a “roadmap” for curtailing the burden posed by disabling hearing impairment was outlined in a resolution of the World Health Assembly. While the underlying principle of this roadmap remains valid and relevant, some updating is required to reflect the prevailing epidemiologic transition. We examine the traditional concept and grades of disabling hearing impairment – within the context of the International Classification of Functioning, Disability and Health – as well as the modifications to grading that have recently been proposed by a panel of international experts. The opportunity offered by the emerging global and high-level interest in promoting disability-inclusive post-2015 development goals and disability-free child survival is also discussed. Since the costs of rehabilitative services are so high as to be prohibitive in low- and middle-income countries, the critical role of primary prevention is emphasized. If the goals outlined in the World Health Assembly’s 1995 resolution on the prevention of hearing impairment are to be reached by Member States, several effective country-level initiatives – including the development of public–private partnerships, strong leadership and measurable time-bound targets – will have to be implemented without further delay. PMID:24839326

  16. First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia.

    PubMed

    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

  17. Determining foot and ankle impairments by the AMA fifth edition guides.

    PubMed

    Harper, Jay D

    2002-06-01

    The fifth edition of the Guides has been criticized for its failure to provide a comprehensive, valid, reliable, unbiased, and evidenced-based system for rating impairments and the way in which workers' compensation systems use the ratings, resulting in inappropriate compensation [8]. The lower extremity chapter utilizes numerous functional and anatomic methods of assessment, as well as diagnosis-based estimates. Though this process of using multiple approaches to measure impairment increases the chances that an underlying physical impairment may be detected, it is time-consuming and may increase rating variability [9]. McCarthy et al studied the correlation between measures of impairment for patients with fractures of the lower extremity. They found that the anatomic approach of evaluation was better correlated than functional and diagnostic methods with measures of task performance based on direct observations as well as the patient's own assessment of activity limitation and disability. Also, muscle strength assessment as described in the Guides was a more sensitive measure of impairment than range of motion [9]. The most elusive part of the foot and ankle evaluation is the inability to capture the added impairment burden caused by pain. The assessment of pain is the most problematic part of any evaluation. Pain is considered and incorporated into the impairment ratings found in the foot and ankle section, as well as the other individual chapters. Chronic pain is often not adequately accounted for, however, and the examiner must evaluate permanent impairment from chronic pain separately. The examiner has the ability to increase the percentage of organ system impairment from 1% to 3% if there is pain-related impairment that increases the burden of illness slightly. If there is significant pain-related impairment, a formal pain assessment is performed. Chapter 18 provides guidance in making these determinations. Impairments for Complex Regional Pain syndrome (CRPS

  18. Physical Impairment

    NASA Astrophysics Data System (ADS)

    Trewin, Shari

    Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

  19. Drugs and Targets in Fibrosis

    PubMed Central

    Li, Xiaoyi; Zhu, Lixin; Wang, Beibei; Yuan, Meifei; Zhu, Ruixin

    2017-01-01

    Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed. PMID:29218009

  20. Deprescribing Benzodiazepines in Older Patients: Impact of Interventions Targeting Physicians, Pharmacists, and Patients.

    PubMed

    Ng, Brendan J; Le Couteur, David G; Hilmer, Sarah N

    2018-04-28

    Benzodiazepines (BZDs; including the related Z-drugs) are frequently targets for deprescribing; long-term use in older people is harmful and often not beneficial. BZDs can result in significant harms, including falls, fractures, cognitive impairment, car crashes and a significant financial and legal burden to society. Deprescribing BZDs is problematic due to a complex interaction of drug, patient, physician and systematic barriers, including concern about a potentially distressing but rarely fatal withdrawal syndrome. Multiple studies have trialled interventions to deprescribe BZDs in older people and are discussed in this narrative review. Reported success rates of deprescribing BZD interventions range between 27 and 80%, and this variability can be attributed to heterogeneity of methodological approaches and limited generalisability to cognitively impaired patients. Interventions targeting the patient and/or carer include raising awareness (direct-to-consumer education, minimal interventions, and 'one-off' geriatrician counselling) and resourcing the patient (gradual dose reduction [GDR] with or without cognitive behavioural therapy, teaching relaxation techniques, and sleep hygiene). These are effective if the patient is motivated to cease and is not significantly cognitively impaired. Interventions targeted to physicians include prescribing interventions by audit, algorithm or medication review, and providing supervised GDR in combination with medication substitution. Pharmacists have less frequently been the targets for studies, but have key roles in several multifaceted interventions. Interventions are evaluated according to the Behaviour Change Wheel. Research supports trialling a stepwise approach in the cognitively intact older person, but having a low threshold to use less-consultative methods in patients with dementia. Several resources are available to support deprescribing of BZDs in clinical practice, including online protocols.

  1. The Use of Robotics to Promote Computing to Pre-College Students with Visual Impairments

    ERIC Educational Resources Information Center

    Ludi, Stephanie; Reichlmayr, Tom

    2011-01-01

    This article describes an outreach program to broaden participation in computing to include more students with visual impairments. The precollege workshops target students in grades 7-12 and engage students with robotics programming. The use of robotics at the precollege level has become popular in part due to the availability of Lego Mindstorm…

  2. Intrinsic motivation as a mediator between metacognition deficits and impaired functioning in psychosis.

    PubMed

    Luther, Lauren; Firmin, Ruth L; Vohs, Jenifer L; Buck, Kelly D; Rand, Kevin L; Lysaker, Paul H

    2016-09-01

    Poor functioning has long been observed in individuals with psychosis. Recent studies have identified metacognition - one's ability to form complex ideas about oneself and others and to use that information to respond to psychological and social challenges-as being an important determinant of functioning. However, the exact process by which deficits in metacognition lead to impaired functioning remains unclear. This study first examined whether low intrinsic motivation, or the tendency to pursue novel experiences and to engage in self-improvement, mediates the relationship between deficits in metacognition and impaired functioning. We then examined whether intrinsic motivation significantly mediated the relationship when controlling for age, education, symptoms, executive functioning, and social cognition. Mediation models were examined in a cross-sectional data set. One hundred and seventy-five individuals with a psychotic disorder completed interview-based measures of metacognition, intrinsic motivation, symptoms, and functioning and performance-based measures of executive functioning and social cognition. Analyses revealed that intrinsic motivation mediated the relationship between metacognition deficits and impaired functioning (95% CI of indirect effect [0.12-0.43]), even after controlling for the aforesaid variables (95% CI of indirect effect [0.04-0.29]). Results suggest that intrinsic motivation may be a mechanism that underlies the link between deficits in metacognition and impaired functioning and indicate that metacognition and intrinsic motivation may be important treatment targets to improve functioning in individuals with psychosis. The findings of this study suggest that deficits in metacognition may indirectly lead to impaired functioning through their effect on intrinsic motivation in individuals with psychosis. Psychological treatments that target deficits in both metacognition and intrinsic motivation may help to alleviate impaired functioning in

  3. A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth

    NASA Astrophysics Data System (ADS)

    Holmgren, Lars; Ambrosino, Elena; Birot, Olivier; Tullus, Carl; Veitonmäki, Niina; Levchenko, Tetyana; Carlson, Lena-Maria; Musiani, Piero; Iezzi, Manuela; Curcio, Claudia; Forni, Guido; Cavallo, Federica; Kiessling, Rolf

    2006-06-01

    Endogenous angiogenesis inhibitors have shown promise in preclinical trials, but clinical use has been hindered by low half-life in circulation and high production costs. Here, we describe a strategy that targets the angiostatin receptor angiomotin (Amot) by DNA vaccination. The vaccination procedure generated antibodies that detected Amot on the endothelial cell surface. Purified Ig bound to the endothelial cell membrane and inhibited endothelial cell migration. In vivo, DNA vaccination blocked angiogenesis in the matrigel plug assay and prevented growth of transplanted tumors for up to 150 days. We further demonstrate that a combination of DNA vaccines encoding Amot and the extracellular and transmembrane domains of the human EGF receptor 2 (Her-2)/neu oncogene inhibited breast cancer progression and impaired tumor vascularization in Her-2/neu transgenic mice. No toxicity or impairment of normal blood vessels could be detected. This work shows that DNA vaccination targeting Amot may be used to mimic the effect of angiostatin. cancer vaccines | neoplasia | neovascularization | breast cancer | angiostatin

  4. Functional imaging correlates of impaired distractor suppression following sleep deprivation.

    PubMed

    Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

    2012-05-15

    Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

    PubMed

    Sato, Tomohiro; Tamada, Tsutomu; Watanabe, Shigeru; Nishimura, Hirotake; Kanki, Akihiko; Noda, Yasufumi; Higaki, Atsushi; Yamamoto, Akira; Ito, Katsuyoshi

    2015-06-01

    This study was undertaken to quantify tissue gadolinium (Gd) deposition in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution among major organs as possible triggers for nephrogenic systemic fibrosis. Five hepatorenally impaired rats (5/6-nephrectomized, with carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA. Histological assessment was conducted and Gd content of the skin, liver, kidneys, lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In addition, five renally impaired rats were injected with Gd-EOB-DTPA and the degree of tissue Gd deposition was compared with that in the hepatorenally impaired rats. ICP-MS analysis revealed significantly higher Gd deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the hepatorenally impaired group (42.6 ± 20.1, 17.2 ± 6.1, 8.4 ± 3.2 μg/g, respectively) than in the renally impaired group (17.2 ± 7.7, 5.4 ± 2.1, 2.8 ± 0.7 μg/g, respectively); no significant difference was found for other organs. In the hepatorenally impaired group, Gd was predominantly deposited in the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and femoral muscle. Histopathological investigation revealed hepatic fibrosis in the hepatorenally impaired group. Compared with renally impaired rats, tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was significantly increased in the kidneys, spleen, and liver, probably due to the impairment of the dual excretion pathways of the urinary and biliary systems.

  6. Persistent non-verbal memory impairment in remitted major depression - caused by encoding deficits?

    PubMed

    Behnken, Andreas; Schöning, Sonja; Gerss, Joachim; Konrad, Carsten; de Jong-Meyer, Renate; Zwanzger, Peter; Arolt, Volker

    2010-04-01

    While neuropsychological impairments are well described in acute phases of major depressive disorders (MDD), little is known about the neuropsychological profile in remission. There is evidence for episodic memory impairments in both acute depressed and remitted patients with MDD. Learning and memory depend on individuals' ability to organize information during learning. This study investigates non-verbal memory functions in remitted MDD and whether nonverbal memory performance is mediated by organizational strategies whilst learning. 30 well-characterized fully remitted individuals with unipolar MDD and 30 healthy controls matching in age, sex and education were investigated. Non-verbal learning and memory were measured by the Rey-Osterrieth-Complex-Figure-Test (RCFT). The RCFT provides measures of planning, organizational skills, perceptual and non-verbal memory functions. For assessing the mediating effects of organizational strategies, we used the Savage Organizational Score. Compared to healthy controls, participants with remitted MDD showed more deficits in their non-verbal memory function. Moreover, participants with remitted MDD demonstrated difficulties in organizing non-verbal information appropriately during learning. In contrast, no impairments regarding visual-spatial functions in remitted MDD were observed. Except for one patient, all the others were taking psychopharmacological medication. The neuropsychological function was solely investigated in the remitted phase of MDD. Individuals with MDD in remission showed persistent non-verbal memory impairments, modulated by a deficient use of organizational strategies during encoding. Therefore, our results strongly argue for additional therapeutic interventions in order to improve these remaining deficits in cognitive function. Copyright 2009 Elsevier B.V. All rights reserved.

  7. [What is impaired consciousness? Revisiting impaired consciousness as psychiatric concept].

    PubMed

    Kanemoto, Kousuke

    2004-01-01

    For decades, psychiatrists have considered that concepts of impaired consciousness in the study of psychiatry were inconsistent with those applied in the field of neurology, in which the usefulness of the concept of consciousness has long been seriously doubted. Gloor concluded that the concept of consciousness does not further the understanding of seizure mechanisms or brain function, which is the current representative opinion of most epileptologists. Loss of consciousness tends to be reduced to aggregates of individual impairments of higher cognitive functions, and the concept of consciousness is preferably avoided by neurologists by assigning various behavioral disturbances during disturbed consciousness to particular neuropsychological centers. In contrast, psychiatrists, especially those in Europe, are more likely to include phenomena involving problems related to phenomenological intentionality in impaired consciousness. For the present study, we first divided consciousness into vigilance and recursive consciousness, and then attempted to determine what kind of impaired consciousness would be an ideal candidate to represent pure disturbance of recursive consciousness. Then, 4 patients, 1 each with pure amnestic states followed immediately by complex partial seizures, an akinetic mutistic state caused by absence status, and mental diplopia as a manifestation of postictal psychosis, as well as a patient with Alzheimer's disease who gracefully performed Japanese tea ceremony, were studied. Based on our findings, we concluded that impaired consciousness as a generic term in general medicine does not indicate any unitary entity corresponding to some well-demarcated physiological function or constitute a base from which recursive consciousness emerges as a superstructure. From that, we stressed that a pure form of impairment of recursive consciousness could occur without the impaired consciousness named generically in general medicine. Second, following

  8. Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila.

    PubMed

    Drago, Ilaria; Davis, Ronald L

    2016-09-06

    The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn)-a brain region critical for olfactory memory formation-causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Adapting for Impaired Patrons.

    ERIC Educational Resources Information Center

    Schuyler, Michael

    1999-01-01

    Describes how a library, with an MCI Corporation grant, approached the process of setting up computers for the visually impaired. Discusses preparations, which included hiring a visually-impaired user as a consultant and contacting the VIP (Visually Impaired Persons) group; equipment; problems with the graphical user interface; and training.…

  10. Impaired Therapeutic Capacity of Autologous Stem Cells in a Model of Type 2 Diabetes

    PubMed Central

    Shin, Laura

    2012-01-01

    Endogenous stem cells in the bone marrow respond to environmental cues and contribute to tissue maintenance and repair. In type 2 diabetes, a multifaceted metabolic disease characterized by insulin resistance and hyperglycemia, major complications are seen in multiple organ systems. To evaluate the effects of this disease on the endogenous stem cell population, we used a type 2 diabetic mouse model (db/db), which recapitulates these diabetic phenotypes. Bone marrow-derived mesenchymal stem cells (MSCs) from db/db mice were characterized in vitro using flow cytometric cell population analysis, differentiation, gene expression, and proliferation assays. Diabetic MSCs were evaluated for their therapeutic potential in vivo using an excisional splint wound model in both nondiabetic wild-type and diabetic mice. Diabetic animals possessed fewer MSCs, which were proliferation and survival impaired in vitro. Examination of the recruitment response of stem and progenitor cells after wounding revealed that significantly fewer endogenous MSCs homed to the site of injury in diabetic subjects. Although direct engraftment of healthy MSCs accelerated wound closure in both healthy and diabetic subjects, diabetic MSC engraftment produced limited improvement in the diabetic subjects and could not produce the same therapeutic outcomes as in their nondiabetic counterparts in vivo. Our data reveal stem cell impairment as a major complication of type 2 diabetes in mice and suggest that the disease may stably alter endogenous MSCs. These results have implications for the efficiency of autologous therapies in diabetic patients and identify endogenous MSCs as a potential therapeutic target. PMID:23197759

  11. IGF2BP1 enhances an aggressive tumor cell phenotype by impairing miRNA-directed downregulation of oncogenic factors.

    PubMed

    Müller, Simon; Bley, Nadine; Glaß, Markus; Busch, Bianca; Rousseau, Vanessa; Misiak, Danny; Fuchs, Tommy; Lederer, Marcell; Hüttelmaier, Stefan

    2018-04-12

    The oncofetal IGF2 mRNA binding proteins (IGF2BPs) are upregulated in most cancers but their paralogue-specific roles in tumor cells remain poorly understood. In a panel of five cancer-derived cell lines, IGF2BP1 shows highly conserved oncogenic potential. Consistently, the deletion of IGF2BP1 impairs the growth and metastasis of ovarian cancer-derived cells in nude mice. Gene expression analyses in ovarian cancer-derived cells reveal that the knockdown of IGF2BPs is associated with the downregulation of mRNAs that are prone to miRNA regulation. All three IGF2BPs preferentially associate upstream of miRNA binding sites (MBSs) in the 3'UTR of mRNAs. The downregulation of mRNAs co-regulated by miRNAs and IGF2BP1 is abrogated at low miRNA abundance or when miRNAs are depleted. IGF2BP1 associates with these target mRNAs in RISC-free complexes and its deletion enhances their association with AGO2. The knockdown of most miRNA-regulated target mRNAs of IGF2BP1 impairs tumor cell properties. In four primary cancers, elevated synthesis of these target mRNAs is largely associated with upregulated IGF2BP1 mRNA levels. In ovarian cancer, the enhanced expression of IGF2BP1 and most of its miRNA-controlled target mRNAs is associated with poor prognosis. In conclusion, these findings indicate that IGF2BP1 enhances an aggressive tumor cell phenotype by antagonizing miRNA-impaired gene expression.

  12. Sensor-Based Assistive Devices for Visually-Impaired People: Current Status, Challenges, and Future Directions

    PubMed Central

    Elmannai, Wafa; Elleithy, Khaled

    2017-01-01

    The World Health Organization (WHO) reported that there are 285 million visually-impaired people worldwide. Among these individuals, there are 39 million who are totally blind. There have been several systems designed to support visually-impaired people and to improve the quality of their lives. Unfortunately, most of these systems are limited in their capabilities. In this paper, we present a comparative survey of the wearable and portable assistive devices for visually-impaired people in order to show the progress in assistive technology for this group of people. Thus, the contribution of this literature survey is to discuss in detail the most significant devices that are presented in the literature to assist this population and highlight the improvements, advantages, disadvantages, and accuracy. Our aim is to address and present most of the issues of these systems to pave the way for other researchers to design devices that ensure safety and independent mobility to visually-impaired people. PMID:28287451

  13. 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.

    PubMed

    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.

  14. 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

    PubMed Central

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

    2016-01-01

    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. PMID:26834549

  15. Amino acids in a targeted versus a non-targeted metabolomics LC-MS/MS assay. Are the results consistent?

    PubMed

    Klepacki, Jacek; Klawitter, Jost; Klawitter, Jelena; Karimpour-Fard, Anis; Thurman, Joshua; Ingle, Gordon; Patel, Dharmesh; Christians, Uwe

    2016-09-01

    The results of plasma amino acid patterns in samples from kidney transplant patients with good and impaired renal function using a targeted LC-MS/MS amino acid assay and a non-targeted metabolomics assay were compared. EDTA plasma samples were prospectively collected at baseline, 1, 2, 4 and 6months post-transplant (n=116 patients, n=398 samples). Each sample was analyzed using both a commercial amino acid LC-MS/MS assay and a non-targeted metabolomics assay also based on MS/MS ion transitions. The results of both assays were independently statistically analyzed to identify amino acids associated with estimated glomerular filtration rates using correlation and partial least squares-discriminant analysis. Although there was overlap between the results of the targeted and non-targeted metabolomics assays (tryptophan, 1-methyl histidine), there were also substantial inconsistencies, with the non-targeted assay resulting in more "hits" than the targeted assay. Without further verification of the hits detected by the non-targeted discovery assay, this would have led to different interpretation of the results. There were also false negative results when the non-targeted assay was used (hydroxy proline). Several of said discrepancies could be explained by loss of sensitivity during analytical runs for selected amino acids (serine and threonine), retention time shifts, signals above the range of linear detector response and integration of peaks not separated from background and interferences (aspartate) when the non-targeted metabolomics assay was used. Whenever assessment of a specific pathway such as amino acids is the focus of interest, a targeted seems preferable to a non-targeted metabolomics assay. Copyright © 2016. Published by Elsevier Inc.

  16. Aquatic organism passage at road-stream crossings—synthesis and guidelines for effectiveness monitoring

    USGS Publications Warehouse

    Hoffman, Robert L.; Dunham, Jason B.; Hansen, Bruce P.

    2012-01-01

    Restoration and maintenance of passage for aquatic organisms at road-stream crossings represents a major management priority, involving an investment of hundreds of millions of dollars (for example, U.S. Government Accounting Office, 2001). In recent years, passage at hundreds of crossings has been restored, primarily by replacing barrier road culverts with bridges or stream simulation culverts designed to pass all species and all life stages of aquatic life and simulate natural hydro-geomorphic processes (U.S. Forest Service, 2008). The current situation has motivated two general questions: 1. Are current design standards for stream simulation culverts adequately re-establishing passage for aquatic biota? and 2. How do we monitor and evaluate effectiveness of passage restoration? To address the latter question, a national workshop was held in March 2010, in Portland, Oregon. The workshop included experts on aquatic organism passage from across the nation (see table of participants, APPENDIX) who addressed four classes of methods for monitoring effectiveness of aquatic organism passage—individual movement, occupancy, demography, and genetics. This report has been written, in part, for field biologists who will be undertaking and evaluating the effectiveness of aquatic organism passage restoration projects at road-stream crossings. The report outlines basic methods for evaluating road-stream crossing passage impairment and restoration and discusses under what circumstances and conditions each method will be useful; what questions each method can potentially answer; how to design and implement an evaluation study; and points out the fundamental reality that most evaluation projects will require special funding and partnerships among researchers and resource managers. The report is organized into the following sections, which can be read independently: 1. Historical context: In this section, we provide a brief history of events leading up to the present situation

  17. Selective Detection of Target Volatile Organic Compounds in Contaminated Humid Air Using a Sensor Array with Principal Component Analysis

    PubMed Central

    Itoh, Toshio; Akamatsu, Takafumi; Tsuruta, Akihiro; Shin, Woosuck

    2017-01-01

    We investigated selective detection of the target volatile organic compounds (VOCs) nonanal, n-decane, and acetoin for lung cancer-related VOCs, and acetone and methyl i-butyl ketone for diabetes-related VOCs, in humid air with simulated VOC contamination (total concentration: 300 μg/m3). We used six “grain boundary-response type” sensors, including four commercially available sensors (TGS 2600, 2610, 2610, and 2620) and two Pt, Pd, and Au-loaded SnO2 sensors (Pt, Pd, Au/SnO2), and two “bulk-response type” sensors, including Zr-doped CeO2 (CeZr10), i.e., eight sensors in total. We then analyzed their sensor signals using principal component analysis (PCA). Although the six “grain boundary-response type” sensors were found to be insufficient for selective detection of the target gases in humid air, the addition of two “bulk-response type” sensors improved the selectivity, even with simulated VOC contamination. To further improve the discrimination, we selected appropriate sensors from the eight sensors based on the PCA results. The selectivity to each target gas was maintained and was not affected by contamination. PMID:28753948

  18. Hearing impairment and retirement.

    PubMed

    Fischer, Mary E; Cruickshanks, Karen J; Pinto, Alex; Klein, Barbara E K; Klein, Ronald; Dalton, Dayna S

    2014-02-01

    Many factors influence the decision to retire including age, insurance, and pension availability along with physical and mental health. Hearing impairment may be one such factor. The purpose of this study was to compare the 15 yr retirement rate among subjects with and without hearing impairment. Prospective, population-based study. Subjects were participants in the Epidemiology of Hearing Loss Study (EHLS), a longitudinal investigation of age-related hearing loss. Participants who were working full- or part-time in 1993-1995 were included (n = 1410, mean age = 57.8 yr). Data from four EHLS phases (1993-1995, 1998-2000, 2003-2005, and 2009-2010) were analyzed in 2010-2012. Hearing impairment was defined as a pure tone threshold average (at 0.5, 1, 2, and 4 kHz) greater than 25 dB HL in the worse ear. Employment status was determined at each of the four phases. Kaplan-Meier estimates of the cumulative incidence of retirement were calculated, and Cox discrete-time modeling was used to determine the effect of hearing impairment on the rate of retirement. The cumulative incidence of retirement was significantly (p < 0.02) higher in those with a hearing impairment (77%) compared to those without a hearing impairment (74%). After adjustment for age, gender, self-reported health, and history of chronic disease, there was no significant difference in the rate of retirement between those with and without a hearing impairment (hazard ratio [HR] = 0.9, 95% confidence interval (CI) = 0.7, 1.1). Similar results were observed when hearing aid users were excluded, when hearing impairment was based on the better ear thresholds, and when analyses were restricted to those under 65 yr of age and working full-time at baseline. Participants with a hearing impairment were less likely to state that the main reason for retirement was that the time seemed right. Hearing impairment was found to be associated with a higher rate of retirement, but the association was not independent of the

  19. Smoking, drinking, and incident cognitive impairment: a cohort community based study included in the Gospel Oak project

    PubMed Central

    Cervilla, J; Prince, M.; Mann, A.

    2000-01-01

    OBJECTIVES—Recent longitudinal studies have reported that smoking increases risk for cognitive impairment and that moderate alcohol intake could be preventive.The association between both cigarette smoking and alcohol drinking and incident cognitive impairment was studied in a representative population.
METHODS—This is a 1 year prospective population based cohort sudy of all residents aged 65 or over in the electoral ward of Gospel Oak in London, UK (n=889). Cognitive impairment was assessed at baseline and 1 year later using the organic brain syndrome (OBS) cognitive impairment scale from the short CARE structured assessment. Subjects who were cognitively impaired at baseline were excluded from this analysis.
RESULTS—The prevalence of OBS cognitive impairment was 10.4% at index assessment and the 1 year cumulative incidence of cognitive impairment was 5.7%. Cognitive impairment was not associated with use of alcohol, although there was a non-significant association in the direction of a protective effect against onset of cognitive impairment for moderate drinkers compared with non-drinkers and heavy drinkers. Current smoking status predicted cognitive impairment (risk ratio (RR) 3.7; (95% confidence interval (95% CI)=1.1-12.3) independently from sex, age, alcohol, occupational class, education, handicap, depression, and baseline cognitive function.
CONCLUSIONS—Smoking seems to be a prospective risk factor for incident cognitive impairment; thus encouragement of older people to stop smoking could be considered as part of a strategy to reduce the incidence of cognitive impairment.

 PMID:10766894

  20. Impact of age on the association between 24-h ambulatory blood pressure measurements and target organ damage.

    PubMed

    Olesen, Thomas B; Pareek, Manan; Stidsen, Jacob V; Blicher, Marie K; Rasmussen, Susanne; Vishram-Nielsen, Julie K K; Kjaer-Hansen, Kathrine; Olsen, Michael H

    2018-05-17

    The aim of this study was to evaluate the impact of age on the associations between hemodynamic components derived from 24-h ambulatory blood pressure (24-h ABPM) and target organ damage, in apparently healthy, nonmedicated individuals. Twenty-four-hour ABPM and target organ damage (left ventricular mass index, pulse wave velocity, urine albumin : creatinine ratio and carotid atherosclerotic plaques) were evaluated in 1408 individuals. Associations were examined in regression models, stratified for age [middle-aged (41 or 51 years) or elderly (61 or 71 years)], and adjusted for sex, smoking status, and total-cholesterol. In middle-aged individuals, an increase of 10 mmHg in 24-h SBP was independently associated with an increase of 3.8 (2.7-4.8) g/m in LVMI. The effect was nearly doubled in the elderly subgroup, where the same increase resulted in an increase in LVMI of 6.3 (5.0-7.6) g/m (P for interaction <0.01). An increase of 10 mmHg of 24-h SBP was associated with a 6.7% increase in pulse wave velocity in middle-aged individuals and with an 9.1% increase in elderly individuals (P for interaction <0.01). An independent association between 24-h ABPM and urine albumin : creatinine ratio was only observed in the elderly subgroup. Associations between the presence of atherosclerotic plaques and components from 24-h ABPM except 24-h DBP were not modified by age (all P for interaction >0.26). Age enhances the associations between hemodynamic components obtained from 24-h ABPM and measures of arterial stiffness, microvascular damage, and cardiac structure, but not atherosclerosis.

  1. Health-Promoting Nature Access for People with Mobility Impairments: A Systematic Review.

    PubMed

    Zhang, Gaochao; Poulsen, Dorthe V; Lygum, Victoria L; Corazon, Sus S; Gramkow, Marie C; Stigsdotter, Ulrika K

    2017-06-29

    This study systematically evaluated the scientific evidence for health benefits of natural environments for people with mobility impairments. Literature searches based on five categories of terms-target group, nature type, health-related impacts, nature-related activities and accessibility issues-were conducted in four databases (Web of Science, Scopus, CAB ABSTRACT and Medline). Twenty-seven articles from 4196 hits were included in the systematic reviews. We concluded that people with mobility disabilities could gain different health benefits, including physical health benefits, mental health benefits and social health benefits from nature in different kinds of nature contacts ranging from passive contact, active involvement to rehabilitative interventions. Several issues related to the accessibility and use of nature for people with mobility impairments need attention from professionals such as landscape architects, rehabilitative therapists, caregivers and policy makers. The overall quality of methodology of the included studies is not high based on assessment of the Mixed Methods Appraisal Tool (MMAT). Moreover, more randomized controlled trials and longitudinal studies that focus specifically on evidence-based health design of nature for people with mobility impairments in the future are needed.

  2. Core hydrophobicity tuning of a self-assembled particle results in efficient lipid reduction and favorable organ distribution.

    PubMed

    Banik, Bhabatosh; Wen, Ru; Marrache, Sean; Kumar, Anil; Kolishetti, Nagesh; Howerth, Elizabeth W; Dhar, Shanta

    2017-12-21

    Atherosclerosis, the deadliest disease in the United States, arises due to the build up of plaques in the arteries as a result of excessive cholesterol deposition and an impaired cholesterol removal process. High density lipoproteins (HDL), popularly known as "good cholesterol", are naturally occurring nano-sized particles that, along with apolipoproteins, are deployed to maintain cholesterol homeostasis in the body. Both cholesterol efflux, from the fat-laden macrophages in the arteries, and intracellular lipid transport, to deliver cholesterol to the mitochondria of liver cells for metabolism, hold key responsibilities to maintain healthy lipid levels inside the body. We designed a library of nine mitochondria targeted polymer-lipid hybrid nanoparticles (NPs), comprised of completely synthetic yet biodegradable components, that are capable of performing HDL-like functions. Using this library, we optimized a superior mitochondria targeted NP candidate, which can show favourable organ distribution, therapeutic potential, and non-toxic properties. Two targeted NP formulations with optimum NP size, zeta potential, and cholesterol binding and release properties were identified. Lipid reduction and anti-oxidative properties of these two NPs demonstrated cholesterol removal ability. In vivo therapeutic evaluation of the targeted-NP formulations in apolipoprotein E knockout (apoE - / - ) mice indicated lipid reduction and anti-inflammatory properties compared to non-targeted NPs. This synthetic targeted NP with potential abilities to participate in both extra- and intracellular cholesterol transport might potentiate therapeutic interventions for heart diseases.

  3. Targeted polypeptide degradation

    DOEpatents

    Church, George M [Brookline, MA; Janse, Daniel M [Brookline, MA

    2008-05-13

    This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

  4. Aspects of studies on the functional impairment electrohypersensitivity

    NASA Astrophysics Data System (ADS)

    Johansson, Olle

    2010-04-01

    Persons, claiming to suffer from exposure to electromagnetic fields, have been described in the literature. In Sweden, electrohypersensitivity (EHS) is an officially fully recognized functional impairment (i.e., it is not regarded as a disease). Survey studies show that somewhere between 230,000 - 290,000 Swedish men and women - out of a population of 9,000,000 - report a variety of symptoms when being in contact with electromagnetic field (EMF) sources. Swedish electrohypersensitive people have their own handicap organization, The Swedish Association for the Electrohypersensitive, which has its own website in both Swedish and English. This organization is included in the Swedish Disability Federation (Handikappförbundens SamarbetsOrgan; HSO). One aim of our studies has been to investigate possible alterations, in the cellular and neuronal systems of these persons' skin. In summary, it is evident from our preliminary data that various alterations are present in the electrohypersensitive persons' skin that are not indicated in the skin of normal healthy volunteers.

  5. LXR-dependent regulation of macrophage-specific reverse cholesterol transport is impaired in a model of genetic diabesity.

    PubMed

    Errico, Teresa L; Méndez-Lara, Karen Alejandra; Santos, David; Cabrerizo, Núria; Baila-Rueda, Lucía; Metso, Jari; Cenarro, Ana; Pardina, Eva; Lecube, Albert; Jauhiainen, Matti; Peinado-Onsurbe, Julia; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco; Julve, Josep

    2017-08-01

    Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice. This was associated with a significant downregulation of the hepatic LXR targets, including Abcg5/g8. Pharmacologic induction of LXR promoted the delivery of total tracer output into feces in db/db mice, partly due to increased liver and small intestine Abcg5/Abcg8 gene expression. Notably, a favorable upregulation of the hepatic levels of ABCG5/G8 and NR1H3 was also observed postoperatively in morbidly obese patients, suggesting a similar LXR impairment in these patients. In conclusion, our data show that downregulation of the LXR axis impairs cholesterol transfer from macrophages to feces in db/db mice, whereas the induction of the LXR axis partly restores impaired m-RCT by elevating the liver and small intestine expressions of Abcg5/g8. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Can Sediment Total Organic Carbon and Grain Size Be Used to Diagnose Organic Enrichment in Estuaries

    EPA Science Inventory

    Eutrophication (i.e., nutrient enrichment, organic enrichment and oxygen depletion) is one of the most common sources of impairment in 303(d) listed waters in the United States. While eutrophication can eventually cause adverse effects to the benthos, it may be hard to diagnose....

  7. [Complex diagnostic of cognitive impairment].

    PubMed

    Emelin, A Yu; Lobzin, V Yu

    2017-01-01

    In this article, the authors discussed the various aspects of pre-dementia stages of cognitive impairment, predominantly of neurodegenerative etiology. The modern conception of the pathophysiology of initial stages of cognitive impairment, the potential for lifetime pathological markers of amyloidosis and neurodegeneration are discussed. The authors proposed to use the concept of 'early signs of cognitive impairment'. The algorithm of the complex early diagnosis of cognitive impairment as well as the opportunities and prospects of clinical, neuropsychological, neuroimaging and laboratory examination methods are presented. The data on main diseases characterized by cognitive impairment and prospects for the use of new highly informative methods for early and differential diagnosis of Alzheimer's disease and vascular cognitive impairment are discussed.

  8. Distance- and near-visual impairment in rural Chinese adults in Kailu, Inner Mongolia.

    PubMed

    Cheng, Fang; Shan, Li; Song, Wulian; Fan, Pan; Yuan, Huiping

    2016-06-01

    To investigate the prevalence and causes of distance-visual impairment and near-vision impairment in a rural Chinese population in Inner Mongolia. A population-based, cross-sectional study design was used to identify visual impairment in the Chinese aged 40 years and older living in Kailu County, Inner Mongolia. Low vision, blindness and near-visual impairment (NVI) were defined according to World Health Organization (WHO) criteria. The overall prevalence of blindness and visual impairment based on the presenting visual acuity (VA) was 2.2% (95% CI: 1.8-2.6) and 9.8% (95% CI: 8.9-10.6), respectively, and was adjusted to 0.9% (95% CI: 0.6-1.2) and 4.7% (95% CI: 4.1-5.3) using best-corrected visual acuity (BCVA), respectively. Taking the presenting VA into consideration, the leading cause of visual impairment and blindness was cataract (40.3%, 40.9%), followed by uncorrected refractive error (26.6%, 28.2%). According to the BCVA, the main cause of visual impairment and blindness was cataract (48.3%, 41.3%) followed by glaucoma (19.0%, 23.9%). Among the examined subjects, 80.3% had NVI, and 51.7% had presbyopia. Major barriers reported by NVI persons without near correction were lack of money to purchase prescription glasses and poor quality of the available ones (43.2%). Visual impairment is a serious public health problem, and the main causes leading to visual impairment are treatable and preventable in the rural Chinese population in Inner Mongolia. Presbyopia, together with the low rate of spectacles and lack of appropriate refractive and presbyopia spectacles, is highly prevalent in rural China. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Foucault on targets.

    PubMed

    Lynch, John

    2004-01-01

    This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict.

  10. Prefrontal activity and impaired memory encoding strategies in schizophrenia.

    PubMed

    Guimond, Synthia; Hawco, Colin; Lepage, Martin

    2017-08-01

    Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome. Copyright © 2017. Published by Elsevier Ltd.

  11. Toxoplasma gondii impairs memory in infected seniors.

    PubMed

    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.

  12. Synthesis of a biofuel target through conventional organic chemistry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Page, Jordan P.; Robinson, Joshua W.; Albrecht, Karl O.

    In this work, the biofuel target compound 2-ethyl-5,5-dimethylcyclopenta-1,3-diene (1) and its exo isomers (9a and 9b), were successfully synthesized via two different pathways from the common intermediate 4,4-dimethylcyclopent-2-ene-1-one (2). The first pathway produced the endocyclic product as a pure isomer via a triflate intermediate obtained from the ketone 2 in 60% yield, followed by copper catalyzed coupling with ethyl magnesium bromide in 63% yield. The second pathway employed a Grignard reaction with ketone 2, which generated an alcohol that was immediately subjected to mild acid catalyzed elimination upon workup of the previous step to yield a primarily a mixture ofmore » exo diastereomers 9a and 9b in 77% yield. These targets had their fuel properties characterized in a separate study.« less

  13. Physical Education Lessons and Activity Status of Visually Impaired and Sighted Adolescents

    PubMed Central

    Demirturk, Funda; Kaya, Mustafa

    2015-01-01

    Background This study investigated participation in physical education and sports lessons of visually impaired adolescents and their sighted peers and compared their physical activity levels. Material/Methods A total of 22 visually impaired children of mean age 13.59±1.14 years and 31 sighted children aged 13.61±0.50 years participated in the study. A questionnaire prepared for this study was used to investigate participation of visually impaired adolescents and their sighted peers in physical education and sports lessons at school and the problems they encounter while doing sports. The Turkish version of the International Physical Activity Questionnaire – short-form (IPAQ-SF) was used to evaluate the physical activity level of the subjects. Results The results of our study suggest that physical activity levels of visually impaired children and their sighted children were similar (p>0.05). Totally blind children had lower IPAQ scores than those with low vision (p<0.05), and girls were less active physically than boys (p<0.05). There were few differences in physical education lessons of the groups, in taking part in sports-related organizations, and future plans. Conclusions Children in secondary school, especially visually impaired children, need to be more motivated and more encouraged to take part in various sports or physical activities. PMID:26568173

  14. Long-Term Effects of CBT on Social Impairment in Adolescents with ASD.

    PubMed

    Maddox, Brenna B; Miyazaki, Yasuo; White, Susan W

    2017-12-01

    Anxiety interventions involving social skills training and CBT for youth with ASD have shown promise, but few studies have examined the effects on social functioning or the maintenance of treatment gains. This study evaluated change in social skills during a randomized controlled trial of CBT and during the 1-year follow-up for 25 adolescents with ASD and anxiety. We examined the effect of pretreatment social anxiety and loneliness on treatment response. Social impairment improved during treatment and continued to improve through the 3-month follow-up. Although adolescents with higher social anxiety had greater pretreatment social impairment, they showed steeper improvement in social skills during treatment. Loneliness was not a significant predictor of change during treatment. CBT targeting social skills and anxiety can lead to long-term improvements in social functioning.

  15. The head-centered meridian effect: auditory attention orienting in conditions of impaired visuo-spatial information.

    PubMed

    Olivetti Belardinelli, Marta; Santangelo, Valerio

    2005-07-08

    This paper examines the characteristics of spatial attention orienting in situations of visual impairment. Two groups of subjects, respectively schizophrenic and blind, with different degrees of visual spatial information impairment, were tested. In Experiment 1, the schizophrenic subjects were instructed to detect an auditory target, which was preceded by a visual cue. The cue could appear in the same location as the target, separated from it respectively by the vertical visual meridian (VM), the vertical head-centered meridian (HCM) or another meridian. Similarly to normal subjects tested with the same paradigm (Ferlazzo, Couyoumdjian, Padovani, and Olivetti Belardinelli, 2002), schizophrenic subjects showed slower reactions times (RTs) when cued, and when the target locations were on the opposite sides of the HCM. This HCM effect strengthens the assumption that different auditory and visual spatial maps underlie the representation of attention orienting mechanisms. In Experiment 2, blind subjects were asked to detect an auditory target, which had been preceded by an auditory cue, while staring at an imaginary point. The point was located either to the left or to the right, in order to control for ocular movements and maintain the dissociation between the HCM and the VM. Differences between crossing and no-crossing conditions of HCM were not found. Therefore it is possible to consider the HCM effect as a consequence of the interaction between visual and auditory modalities. Related theoretical issues are also discussed.

  16. Evidence for impairments in using static line drawings of eye gaze cues to orient visual-spatial attention in children with high functioning autism.

    PubMed

    Goldberg, Melissa C; Mostow, Allison J; Vecera, Shaun P; Larson, Jennifer C Gidley; Mostofsky, Stewart H; Mahone, E Mark; Denckla, Martha B

    2008-09-01

    We examined the ability to use static line drawings of eye gaze cues to orient visual-spatial attention in children with high functioning autism (HFA) compared to typically developing children (TD). The task was organized such that on valid trials, gaze cues were directed toward the same spatial location as the appearance of an upcoming target, while on invalid trials gaze cues were directed to an opposite location. Unlike TD children, children with HFA showed no advantage in reaction time (RT) on valid trials compared to invalid trials (i.e., no significant validity effect). The two stimulus onset asynchronies (200 ms, 700 ms) did not differentially affect these findings. The results suggest that children with HFA show impairments in utilizing static line drawings of gaze cues to orient visual-spatial attention.

  17. Visual impairment among 10-14-year school children in Puducherry: A cross-sectional study.

    PubMed

    Vishnuprasad, R; Bazroy, Joy; Madhanraj, K; Prashanth, Hannah Ranjee; Singh, Zile; Samuel, Abel K; Muthukumar, T

    2017-01-01

    According to the 2010 estimates by the World Health Organization, nearly 285 million (4.24% of total population) people of all ages worldwide are visually impaired. Almost 18.9 million children under 15 years of age are visually impaired globally. In developing countries, 7%-31% of childhood blindness and visual impairment is avoidable. The study was conducted as a cross-sectional study among 1884 school students in Puducherry, in the age group of 10-14 years. A child with presenting maximum vision ≤6/12 Snellen equivalent in the better eye is considered visually impaired. Data were entered in Microsoft Excel 2013 and analyzed using the statistical software SPSS version 21.0. Chi-square test was applied for testing difference in proportion and a P < 0.05 was considered statistically significant. The overall prevalence of visual impairment (vision ≤6/12) among the study participants was 6.37% (95% confidence interval = 5.27-7.47). The prevalence of visual impairment increased with age and it was found to be high among male students (6.6%) when compared to female students (6%). Presenting vision of 6/6 was observed in 79.8% of the children while with pinhole correction, the proportion increased to 94.6%. The prevalence of visual impairment in our study population was found to be 6.37% and the prevalence was even higher among children who belonged to schools of urban region or private schools. Children with a positive family history of spectacle use were more likely to have visual impairment.

  18. Flying under the radar: figurative language impairments in focal lesion patients

    PubMed Central

    Ianni, Geena R.; Cardillo, Eileen R.; McQuire, Marguerite; Chatterjee, Anjan

    2014-01-01

    Despite the prevalent and natural use of metaphor in everyday language, the neural basis of this powerful communication device remains poorly understood. Early studies of brain-injured patients suggested the right hemisphere plays a critical role in metaphor comprehension, but more recent patient and neuroimaging studies do not consistently support this hypothesis. One explanation for this discrepancy is the challenge in designing optimal tasks for brain-injured populations. As traditional aphasia assessments do not assess figurative language comprehension, we designed a new metaphor comprehension task to consider whether impaired metaphor processing is missed by standard clinical assessments. Stimuli consisted of 60 pairs of moderately familiar metaphors and closely matched literal sentences. Sentences were presented visually in a randomized order, followed by four adjective-noun answer choices (target + three foil types). Participants were instructed to select the phrase that best matched the meaning of the sentence. We report the performance of three focal lesion patients and a group of 12 healthy, older controls. Controls performed near ceiling in both conditions, with slightly more accurate performance on literal than metaphoric sentences. While the Western Aphasia Battery (Kertesz, 1982) and the objects and actions naming battery (Druks and Masterson, 2000) indicated minimal to no language difficulty, our metaphor comprehension task indicated three different profiles of metaphor comprehension impairment in the patients’ performance. Single case statistics revealed comparable impairment on metaphoric and literal sentences, disproportionately greater impairment on metaphors than literal sentences, and selective impairment on metaphors. We conclude our task reveals that patients can have selective metaphor comprehension deficits. These deficits are not captured by traditional neuropsychological language assessments, suggesting overlooked communication

  19. USGS aerial resolution targets.

    USGS Publications Warehouse

    Salamonowicz, P.H.

    1982-01-01

    It is necessary to measure the achievable resolution of any airborne sensor that is to be used for metric purposes. Laboratory calibration facilities may be inadequate or inappropriate for determining the resolution of non-photographic sensors such as optical-mechanical scanners, television imaging tubes, and linear arrays. However, large target arrays imaged in the field can be used in testing such systems. The USGS has constructed an array of resolution targets in order to permit field testing of a variety of airborne sensing systems. The target array permits any interested organization with an airborne sensing system to accurately determine the operational resolution of its system. -from Author

  20. Hearing Impairment and Retirement

    PubMed Central

    Fischer, Mary E; Cruickshanks, Karen J; Pinto, Alex; Klein, Barbara E K; Klein, Ronald; Dalton, Dayna S

    2013-01-01

    BACKGROUND Many factors influence the decision to retire including age, insurance and pension availability along with physical and mental health. Hearing impairment may be one such factor. PURPOSE The purpose of this study was to compare the 15 year retirement rate among subjects with and without hearing impairment. RESEARCH DESIGN Prospective, population-based study STUDY SAMPLE Subjects were participants in the Epidemiology of Hearing Loss Study (EHLS), a longitudinal investigation of age-related hearing loss. Participants who were working full- or part-time in 1993–1995 were included (n=1410, mean age=57.8 years). DATA COLLECTION AND ANALYSIS Data from four EHLS phases (1993–1995, 1998–2000, 2003–2005, and 2009–2010) were analyzed in 2010–2012. Hearing impairment was defined as a pure tone threshold average (at 0.5,1,2 and 4 kHz) greater than 25 dB HL in the worse ear. Employment status was determined at each of the four phases. Kaplan-Meier estimates of the cumulative incidence of retirement were calculated and Cox discrete-time modeling was used to determine the effect of hearing impairment on the rate of retirement. RESULTS The cumulative incidence of retirement was significantly (p < 0.02) higher in those with a hearing impairment (77%) compared to those without a hearing impairment (74%). After adjustment for age, gender, self-reported health, and history of chronic disease, there was no significant difference in the rate of retirement between those with and without a hearing impairment (Hazard Ratio (HR) = 0.9, 95% Confidence Interval (CI) = 0.7, 1.1). Similar results were observed when hearing aid users were excluded, when hearing impairment was based on the better ear thresholds, and when analyses were restricted to those less than 65 years of age and working full-time at baseline. Participants with a hearing impairment were less likely to state that the main reason for retirement was that the time seemed right. CONCLUSIONS Hearing impairment

  1. Cognitive Impairment and Tramadol Dependence.

    PubMed

    Bassiony, Medhat M; Youssef, Usama M; Hassan, Mervat S; Salah El-Deen, Ghada M; El-Gohari, Hayam; Abdelghani, Mohamed; Abdalla, Ahmed; Ibrahim, Dalia H

    2017-02-01

    Cognitive impairment is one of the consequences of substance abuse. Tramadol abuse is a public health problem in Egypt. The objective of this study was to estimate the prevalence and correlates of cognitive impairment among tramadol-abuse patients and control subjects. This study included 100 patients with tramadol abuse and 100 control subjects (matched for age, sex, and education) who were recruited from Zagazig University Hospital, Egypt. Patients were divided into 2 groups: patients who used tramadol only (tramadol-alone group) and patients who used tramadol and other substances (polysubstance group). The participants were interviewed using Montreal Cognitive Assessment test and had urine screening for drugs. Twenty-four percent of the cases used tramadol alone, whereas the remaining used tramadol and other substances, mainly cannabis (66%) and benzodiazepines (27%). Tramadol-abuse patients were about 3 times more likely to have cognitive impairment than control subjects (81% vs 28%). Tramadol-alone patients were more than 2 times more likely to have cognitive impairment than control subjects (67% vs 28%). Cognitive impairment was significantly associated with polysubstance abuse. There was no association between cognitive impairment and sociodemographic or clinical factors. Cognitive impairment occurs commonly among tramadol-abuse patients. Memory impairment is the most common cognitive domain to be affected. There is a significant association between cognitive impairment and polysubstance abuse.

  2. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

    PubMed

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-02-01

    Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

  3. Relationships: Marriage and Family Life of Hearing-Impaired People Living in the Mainstream.

    ERIC Educational Resources Information Center

    Rice, Daisy N.

    1984-01-01

    The development of relationships among families of hearing impaired persons is traced through the cycles of the marriage, parent-child relationship, and child and peer interaction. Impact of environment (home vs. residential school), society, economic stability, and social organization and lifestyle is analyzed, and stages in personal development…

  4. Psychogenic and organic amnesia: a multidimensional assessment of clinical, neuroradiological, neuropsychological and psychopathological features.

    PubMed

    Serra, Laura; Fadda, Lucia; Buccione, Ivana; Caltagirone, Carlo; Carlesimo, Giovanni A

    2007-01-01

    Psychogenic amnesia is a complex disorder characterised by a wide variety of symptoms. Consequently, in a number of cases it is difficult distinguish it from organic memory impairment. The present study reports a new case of global psychogenic amnesia compared with two patients with amnesia underlain by organic brain damage. Our aim was to identify features useful for distinguishing between psychogenic and organic forms of memory impairment. The findings show the usefulness of a multidimensional evaluation of clinical, neuroradiological, neuropsychological and psychopathological aspects, to provide convergent findings useful for differentiating the two forms of memory disorder.

  5. Indirect interception actions by blind and visually impaired perceivers: echolocation for interceptive actions.

    PubMed

    Vernat, Jean-Philippe; Gordon, Michael S

    2010-02-01

    This research examined the acoustic information used to support interceptive actions by the blind. Congenitally blind and severely visually impaired participants (all wearing an opaque, black eye-mask) were asked to listen to a target ball rolling down a track. In response, participants rolled their own ball along a perpendicular path to intercept the target. To better understand what information was used the echoic conditions and rolling dynamics of the target were varied across test sessions. In addition the rolling speed of the target and the distance of the participant from the target were varied across trials. Results demonstrated that participants tended to perform most accurately at moderate speeds and distances, overestimating the target's arrival at the fastest speed, and underestimating it at the slowest speed. However, changes to the target's dynamics, that is, the amount of deceleration it underwent on approach, did not strongly influence performance. Echoic conditions were found to affect performance, as participants were slightly more accurate in conditions with faster, higher-intensity echoes. Based on these results blind individuals in this research seemed to be using spatial and temporal cues to coordinate their interceptive actions.

  6. Neonatal agonism of ERβ impairs male reproductive behavior and attractiveness

    PubMed Central

    Sullivan, Alana W.; Hamilton, Peter; Patisaul, Heather B.

    2011-01-01

    The organization of the developing male rodent brain is profoundly influenced by endogenous steroids, most notably estrogen. This process may be disrupted by estrogenic endocrine disrupting compounds (EDCs) resulting in altered sex behavior and the capacity to attract a mate in adulthood. To better understand the relative role each estrogen receptor (ER) subtype (ERα and ERβ) plays in mediating these effects, we exposed male Long Evans rats to estradiol benzoate (EB, 10 μg), vehicle, or agonists specific for ERβ (DPN, 1 mg/kg) or ERα (PPT, 1 mg/kg) daily for the first four days of life, and then assessed adult male reproductive behavior and attractiveness via a partner preference paradigm. DPN had a greater adverse impact than PPT on reproductive behavior, suggesting a functional role for ERβ in the organization of these male-specific behaviors. Therefore the impact of neonatal ERβ agonism was further investigated by repeating the experiment using vehicle, EB and additional DPN doses (0.5 mg/kg, 1 mg/kg, and 2 mg/kg bw). Exposure to DPN suppressed male reproductive behavior and attractiveness in a dose dependent manner. Finally, males were exposed to EB or an environmentally relevant dose of genistein (GEN, 10 mg/kg), a naturally occurring xenoestrogen, which has a higher relative binding affinity for ERβ than ERα. Sexual performance was impaired by GEN but not attractiveness. In addition to suppressing reproductive behavior and attractiveness, EB exposure significantly lowered the testis to body weight ratio, and circulating testosterone levels. DPN and GEN exposure only impaired behavior, suggesting that disrupted androgen secretion does not underlie the impairment. PMID:21554883

  7. Investigating an organ-targeting platform based on hydroxyapatite nanoparticles using a novel in situ method of radioactive ¹²⁵Iodine labeling.

    PubMed

    Ignjatović, Nenad; Vranješ Djurić, Sanja; Mitić, Zarko; Janković, Drina; Uskoković, Dragan

    2014-10-01

    In this study, we have investigated the synthesis of nanoparticles of hydroxyapatite (HAp) and hydroxyapatite coated with chitosan (HAp/Ch) and the chitosan-poly-d,l-lactide-co-glycolide polymer blend (HAp/Ch-PLGA) as an organ-targeting system. We have examined and defined the final destination, as well as the dynamics and the pathways of the synthesized particles following intravenous administration in vivo. The XRD, ZP, FT-IR and SEM analyses have confirmed that the hydroxyapatite nanoparticles with d50=72 nm are coated with polymers. Radioactive 125-Iodine ((125)I), a low energy gamma emitter, was used to develop a novel in situ method for the radiolabeling of particles and investigation of their biodistribution. (125)I-labeled particles exhibited high stability in saline and serum over the second day, which justified their use in the following in vivo studies. The biodistribution of (125)I-labeled particles after intravenous injection in rats differed significantly: HAp particles mostly targeted the liver, HAp/Ch the spleen and the liver, while HAp/Ch-PLGA targeted the lungs. Twenty-four hours post injection, HAp particles were excreted completely, while both (125)I-HAp/Ch and (125)I-HAp/Ch-PLGA were retained in the body for a prolonged period of time with more than 20% of radioactivity still found in different organs. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Physical activity and physical fitness of nursing home residents with cognitive impairment: A pilot study.

    PubMed

    Marmeleira, José; Ferreira, Soraia; Raimundo, Armando

    2017-12-15

    Physical activity and physical fitness are important for health, functional mobility and performance of everyday activities. To date, little attention has been given to physical activity and physical fitness among nursing home residents with cognitive impairment. Therefore, the main aim of this study was to examine physical activity behavior and physical fitness of institutionalized older adults with cognitive impairment and to investigate their interrelations. Forty-eight older adults with cognitive impairment (83.9±7.7years; 72.9% women) and 22 without cognitive impairment (82.2±8.8years; 54.5% women) participated. Physical activity was objectively assessed with accelerometers and physical fitness components (muscular strength, flexibility, balance, body composition and reaction time) were evaluated with physical fitness field tests. Nursing home residents with cognitive impairment spent only ~1min per day in moderate physical activity and ~89min in light physical activity. In average they accumulated 863 (±599) steps per day and spent 87.2% of the accelerometer wear time in sedentary behavior. Participants' physical fitness components were markedly low and according to the cut-offs used for interpreting the results a great number of nursing home residents had an increased risk of associated health problems, functional impairment and of falling. The performance in some physical fitness tests was positively associated with physical activity. Participants without cognitive impairment had higher levels of physical activity and physical fitness than their counterparts with cognitive impairment. These results indicate that nursing home residents, especially those with cognitive impairment, have low levels of physical activity, spent a high proportion of daytime in sedentary behavior and have low physical fitness. Nursing homes should implement health promotion strategies targeting physical activity and physical fitness of their residents. Copyright © 2017 Elsevier

  9. Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation.

    PubMed

    Nilsson, Jonas A; Keller, Ulrich B; Baudino, Troy A; Yang, Chunying; Norton, Sara; Old, Jennifer A; Nilsson, Lisa M; Neale, Geoffrey; Kramer, Debora L; Porter, Carl W; Cleveland, John L

    2005-05-01

    Checkpoints that control Myc-mediated proliferation and apoptosis are bypassed during tumorigenesis. Genes encoding polyamine biosynthetic enzymes are overexpressed in B cells from E mu-Myc transgenic mice. Here, we report that disabling one of these Myc targets, Ornithine decarboxylase (Odc), abolishes Myc-induced suppression of the Cdk inhibitors p21(Cip1) and p27(Kip1), thereby impairing Myc's proliferative, but not apoptotic, response. Moreover, lymphoma development was markedly delayed in E mu-Myc;Odc(+/-) transgenic mice and in E mu-Myc mice treated with the Odc inhibitor difluoromethylornithine (DFMO). Strikingly, tumors ultimately arising in E mu-Myc;Odc(+/-) transgenics lacked deletions of Arf, suggesting that targeting Odc forces other routes of transformation. Therefore, Odc is a critical Myc transcription target that regulates checkpoints that guard against tumorigenesis and is an effective target for cancer chemoprevention.

  10. The Development of the Navigation System for Visually Impaired Persons

    DTIC Science & Technology

    2001-10-25

    method) is used in our system. In this papaer , we re- fer to the developed methods which are the positioning method without DGPS and the method of the...University Kanagawa, Japan Performing Organization Report Number Sponsoring/Monitoring Agency Name(s) and Address(es) US Army Research , Development...impaired. ACKNOWLEDGMENT This research was partially supported by the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scienti c

  11. 20 CFR 220.104 - Multiple impairments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... physical or mental impairment or impairments are of a sufficient medical severity that such impairment or... throughout the disability evaluation process. If a medically severe combination of impairments is not found...

  12. The Process of Auditory Distraction: Disrupted Attention and Impaired Recall in a Simulated Lecture Environment

    ERIC Educational Resources Information Center

    Zeamer, Charlotte; Fox Tree, Jean E.

    2013-01-01

    Literature on auditory distraction has generally focused on the effects of particular kinds of sounds on attention to target stimuli. In support of extensive previous findings that have demonstrated the special role of language as an auditory distractor, we found that a concurrent speech stream impaired recall of a short lecture, especially for…

  13. Increased homocysteine levels impair reference memory and reduce cortical levels of acetylcholine in a mouse model of vascular cognitive impairment.

    PubMed

    Dam, Kevin; Füchtemeier, Martina; Farr, Tracy D; Boehm-Sturm, Philipp; Foddis, Marco; Dirnagl, Ulrich; Malysheva, Olga; Caudill, Marie A; Jadavji, Nafisa M

    2017-03-15

    Folates are B-vitamins that are vital for normal brain function. Deficiencies in folates either genetic (methylenetetrahydrofolate reductase, MTHFR) or dietary intake of folic acid result in elevated levels of homocysteine. Clinical studies have shown that elevated levels of homocysteine (Hcy) may be associated with the development of dementia, however this link remains unclear. The purpose of this study was to evaluate the impact of increased Hcy levels on a mouse model of vascular cognitive impairment (VCI) produced by chronic hypoperfusion. Male and female Mthfr +/+ and Mthfr +/- mice were placed on either control (CD) or folic acid deficient (FADD) diets after which all animals underwent microcoil implantation around each common carotid artery or a sham procedure. Post-operatively animals were tested on the Morris water maze (MWM), y-maze, and rotarod. Animals had no motor impairments on the rotarod, y-maze, and could learn the location of the platform on the MWM. However, on day 8 of testing of MWM testing during the probe trial, Mthfr +/- FADD microcoil mice spent significantly less time in the target quadrant when compared to Mthfr +/- CD sham mice, suggesting impaired reference memory. All FADD mice had elevated levels of plasma homocysteine. MRI analysis revealed arterial remodeling was present in Mthfr +/- microcoil mice not Mthfr +/+ mice. Acetylcholine and related metabolites were reduced in cortical tissue because of microcoil implantation and elevated levels of homocysteine. Deficiencies in folate metabolism resulting in increased Hcy levels yield a metabolic profile that increases susceptibility to neurodegeneration in a mouse model of VCI. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Manneristic behaviors of visually impaired children.

    PubMed

    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

  15. Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis.

    PubMed

    Hughes, Abbey J; Parmenter, Brett A; Haselkorn, Jodie K; Lovera, Jesus F; Bourdette, Dennis; Boudreau, Eilis; Cameron, Michelle H; Turner, Aaron P

    2017-08-01

    Problems with sleep and cognitive impairment are common among people with multiple sclerosis (MS). The present study examined the relationship between self-reported sleep and both objective and perceived cognitive impairment in MS. Data were obtained from the baseline assessment of a multi-centre intervention trial (NCT00841321). Participants were 121 individuals with MS. Nearly half (49%) of participants met the criteria for objective cognitive impairment; however, cognitively impaired and unimpaired participants did not differ on any self-reported sleep measures. Nearly two-thirds (65%) of participants met the criteria for 'poor' sleep, and poorer sleep was significantly associated with greater levels of perceived cognitive impairment. Moreover, the relationships between self-reported sleep and perceived cognitive impairment were significant beyond the influence of clinical and demographic factors known to influence sleep and cognitive functioning (e.g. age, sex, education level, disability severity, type of MS, disease duration, depression and fatigue). However, self-reported sleep was not associated with any measures of objective cognitive impairment. Among different types of perceived cognitive impairment, poor self-reported sleep was most commonly related to worse perceived executive function (e.g. planning/organization) and prospective memory. Results from the present study emphasize that self-reported sleep is significantly and independently related to perceived cognitive impairment in MS. In terms of clinical implications, interventions focused on improving sleep may help improve perceived cognitive function and quality of life in this population; however, the impact of improved sleep on objective cognitive function requires further investigation. © 2017 European Sleep Research Society.

  16. NF-κB activation impairs somatic cell reprogramming in ageing.

    PubMed

    Soria-Valles, Clara; Osorio, Fernando G; Gutiérrez-Fernández, Ana; De Los Angeles, Alejandro; Bueno, Clara; Menéndez, Pablo; Martín-Subero, José I; Daley, George Q; Freije, José M P; López-Otín, Carlos

    2015-08-01

    Ageing constitutes a critical impediment to somatic cell reprogramming. We have explored the regulatory mechanisms that constitute age-associated barriers, through derivation of induced pluripotent stem cells (iPSCs) from individuals with premature or physiological ageing. We demonstrate that NF-κB activation blocks the generation of iPSCs in ageing. We also show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs the generation of iPSCs by eliciting the reprogramming repressor DOT1L, which reinforces senescence signals and downregulates pluripotency genes. Genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo progeria syndrome and Hutchinson-Gilford progeria syndrome patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo extends lifespan and ameliorates the accelerated ageing phenotype of progeroid mice, supporting the interest of studying age-associated molecular impairments to identify targets of rejuvenation strategies.

  17. Formulation of multifunctional oil-in-water nanosized emulsions for active and passive targeting of drugs to otherwise inaccessible internal organs of the human body.

    PubMed

    Tamilvanan, Shunmugaperumal

    2009-10-20

    Oil-in-water (o/w) type nanosized emulsions (NE) have been widely investigated as vehicles/carrier for the formulation and delivery of drugs with a broad range of applications. A comprehensive summary is presented on how to formulate the multifunctional o/w NE for active and passive targeting of drugs to otherwise inaccessible internal organs of the human body. The NE is classified into three generations based on its development over the last couple of decades to make ultimately a better colloidal carrier for a target site within the internal and external organs/parts of the body, thus allowing site-specific drug delivery and/or enhanced drug absorption. The third generation NE has tremendous application for drug absorption enhancement and for 'ferrying' compounds across cell membranes in comparison to its first and second generation counterparts. Furthermore, the third generation NE provides an interesting opportunity for use as drug delivery vehicles for numerous therapeutics that can range in size from small molecules to macromolecules.

  18. [Functional impairment associated with cognitive impairment in hospitalised elderly].

    PubMed

    Ocampo-Chaparro, José Mauricio; Mosquera-Jiménez, José Ignacio; Davis, Annabelle S; Reyes-Ortiz, Carlos A

    The aim of this study was to analyse the effect of cognitive impairment on functional decline in hospitalised patients aged ≥60 years. Measurements at admission included demographic data, Charlson's comorbidity index, and cognitive impairment (according to education level). Data were also collected on hospital length of stay, depression, and delirium developed during hospitalisation. The outcome, Barthel Index (BI), was measured at admission, discharge, and 1-month post-discharge. Patients with BI≤75 at admission (n=54) or with a missing BI value were excluded (n=1). Multivariate logistic regression analyses were conducted to explore predictive factors with functional decline (BI≤75) from admission to discharge, and 1-month later. Of the 133 patients included, 24.8% and 19.6% had a BI≤75 at discharge and at 1-month, respectively. Compared with men, women had more than double risk for functional decline at discharge and 1-month (P<.05). Compared with those without delirium and without cognitive impairment, those with delirium and cognitive impairment had an increased risk for functional decline (BI≤75) at discharge (OR 5.15, 95% CI; 1.94-13.67), and at 1-month (OR 6.26, 95% CI; 2.30-17.03). Similarly, those with comorbidity (≥2) had increased functional decline at discharge (OR 2.36, 95% CI; 1.14-4.87), and at 1-month after discharge (OR 2.71, 95% CI; 1.25-5.89). Delirium during hospitalisation, together with cognitive impairment on admission, was a strong predictor of functional decline. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Radar Imaging for Moving Targets

    DTIC Science & Technology

    2009-06-01

    MOVING TARGETS by Teo Beng Koon William June 2009 Thesis Advisor: Brett H. Borden Second Reader: Donald L. Walters THIS PAGE...Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project...TITLE AND SUBTITLE Radar Imaging for Moving Targets 6. AUTHOR(S) Teo Beng Koon William 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S

  20. Prevalence and Causes of Visual Impairment and Blindness in Shanxi Province, China.

    PubMed

    Li, Tong; Du, Liping; Du, Lingzhen

    2015-01-01

    To estimate the prevalence and causes of visual impairment and blindness in Shanxi Province, China. Data were obtained from the Second National Sampling Survey of Disability conducted in 2006. Blindness and visual impairment were defined as best corrected visual acuity <3/60 and <6/18, respectively, in the better-seeing eye. Standardized ophthalmologic examinations were administered to participants aged 0-80 years in 2006. Visual acuity (VA) was measured using a Standard Logarithmic Visual Acuity E chart (Snellen) for subjects aged 7 years and older. Participants younger than 7 years were examined using special experiments or the Childhood Graphical Visual Chart. The prevalence of visual impairment and blindness in Shanxi was estimated to be 0.6% (466/75,016) among persons up to 80 years old. The prevalence in rural areas (0.7%; 351/48,137) was significantly higher than that in urban areas (0.4%; 115/26,879) and was higher in females (0.8%; 298/36,933) than in males (0.4%; 168/38,083). The most common cause of visual impairment and blindness was cataract (44.9%), followed by retinopathy and choroidopathy (12.5%), hereditary and developmental disorders (10.3%), corneal disease (5.2%), and refractive error (4.9%). Prevalences of visual impairment and blindness in women and in rural areas were higher than in men and urban areas, and increased with age. Cataract was the most prevalent cause of visual impairment and blindness. Based on the findings from this study, we suggest that provision of support and welfare services should be organized.