WorldWideScience

Sample records for improved long-term expression

  1. Memory effect in expressed emotions during long term group interactions

    NARCIS (Netherlands)

    Gorbunov, R.; Barakova, E.I.; Rauterberg, M.; Ferrández Vicente, J.M.; Álvarez-Sánchez, J.R.; de la Paz López, F.; Toledo Moreo, J.; Adeli, H.

    2017-01-01

    Long-term interactions in groups can be monitored through games in which the participants need to show their social preferences by making choice to help or to use egoistic game strategy. In this paper we analyse the facial expressions of a group of isolated individuals (astronauts) during repeated

  2. Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino.

    Science.gov (United States)

    Wu, Bo; Lu, Peijuan; Cloer, Caryn; Shaban, Mona; Grewal, Snimar; Milazi, Stephanie; Shah, Sapana N; Moulton, Hong M; Lu, Qi Long

    2012-08-01

    Exon skipping is capable of correcting frameshift and nonsense mutations in Duchenne muscular dystrophy. Phase 2 clinical trials in the United Kingdom and the Netherlands have reported induction of dystrophin expression in muscle of Duchenne muscular dystrophy patients by systemic administration of both phosphorodiamidate morpholino oligomers (PMO) and 2'-O-methyl phosphorothioate. Peptide-conjugated phosphorodiamidate morpholino offers significantly higher efficiency than phosphorodiamidate morpholino, with the ability to induce near-normal levels of dystrophin, and restores function in both skeletal and cardiac muscle. We examined 1-year systemic efficacy of peptide-conjugated phosphorodiamidate morpholino targeting exon 23 in dystrophic mdx mice. The LD(50) of peptide-conjugated phosphorodiamidate morpholino was determined to be approximately 85 mg/kg. The half-life of dystrophin expression was approximately 2 months in skeletal muscle, but shorter in cardiac muscle. Biweekly injection of 6 mg/kg peptide-conjugated phosphorodiamidate morpholino produced >20% dystrophin expression in all skeletal muscles and ≤5% in cardiac muscle, with improvement in muscle function and pathology and reduction in levels of serum creatine kinase. Monthly injections of 30 mg/kg peptide-conjugated phosphorodiamidate morpholino restored dystrophin to >50% normal levels in skeletal muscle, and 15% in cardiac muscle. This was associated with greatly reduced serum creatine kinase levels, near-normal histology, and functional improvement of skeletal muscle. Our results demonstrate for the first time that regular 1-year administration of peptide-conjugated phosphorodiamidate morpholino can be safely applied to achieve significant therapeutic effects in an animal model. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. On improving the NPP construction long-term planning

    International Nuclear Information System (INIS)

    Solov'ev, M.M.

    1980-01-01

    General approaches to solving the problems of long-term planning of the construction-mounting work volume and introduction of power capacities at different paces of power unit commission and norms of construction time are considered. Problems associated with location and development of subsidiary industries providing NPP construction are discussed. It is shown that decrease of WWER-1000 reactor type NPP construction time from 24 to 12 months results in reduction of required high-skilled engineers, managerial staff, unique construction mechanisms and engines as well as in improvement of conditions for conducting measures on work arrangement during preparation of construction industry and mounting of the first assemblies

  4. Improving students' long-term knowledge retention through personalized review.

    Science.gov (United States)

    Lindsey, Robert V; Shroyer, Jeffery D; Pashler, Harold; Mozer, Michael C

    2014-03-01

    Human memory is imperfect; thus, periodic review is required for the long-term preservation of knowledge and skills. However, students at every educational level are challenged by an ever-growing amount of material to review and an ongoing imperative to master new material. We developed a method for efficient, systematic, personalized review that combines statistical techniques for inferring individual differences with a psychological theory of memory. The method was integrated into a semester-long middle-school foreign-language course via retrieval-practice software. Using a cumulative exam administered after the semester's end, we compared time-matched review strategies and found that personalized review yielded a 16.5% boost in course retention over current educational practice (massed study) and a 10.0% improvement over a one-size-fits-all strategy for spaced study.

  5. ComfortPower - System improvements and long-term evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Silversand, Fredrik [Catator AB, Lund (Sweden)

    2011-11-15

    Catator has previously developed a novel heating system abbreviated ComfortPower in a RandD-programme supported by Catator, Swedish Gas Centre (SGC), Swedish Defence Materiel Administration (FMV), Skanska, Nibe and Alfa Laval. The ComfortPower unit comprises a multi fuel reformer system tied to a high-temperature polymer electrolyte fuel cell (HT-PEM) and a heat pump system. Since the residual heat from the fuel cell system can be utilized in a very effective way, it is possible to reach high thermal efficiencies. Indeed, the thermal efficiency in the unit has previously been shown to reach values as high as 175 - 200 % based on the lower heating value of the fuel. In addition to heat, ComfortPower can supply comfort cooling and surplus electricity. This project phase has focused on the following elements: 1. System improvements to further enhance the efficiency with existing fuel cell (HT-PEM). 2. System simplifications (e.g. DC-compressor system) to manage issues with start-up currents. 3. Tests with biogas qualities (various levels of CO{sub 2}) and biogas/air. 4. Long-term test with biogas quality (upgraded biogas). 5. Additional tests with liquid fuels (alcohols and diesel). 6. Map the need for cooling and heating in various applications. 7. Investigate how ComfortPower can reduce the primary energy consumption and reduce the environmental impact. 8. Study the possibility with a SOFC-based system with internal reforming. It was found that the Optiformer technology can be used to derive a suitable reformate gas for the HT-PEM unit from a wide range of fuels. Even if operation with fuel gases is the natural choice in most cases, it is possible also to use alcohols and other liquid fuels (e.g. in Campus applications). The heat pump system was equipped with a 24 V DC-compressor provided by Nibe. The compressor could be directly powered by the accumulator system and start-up currents, harmful to the inverter, could be avoided. Some improvements were made on the

  6. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*

    Science.gov (United States)

    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert

    2016-01-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

  7. Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation.

    Science.gov (United States)

    Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert; Michaelevski, Izhak

    2016-02-01

    Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein

  8. Long-term expression of glomerular genes in diabetic nephropathy.

    Science.gov (United States)

    Chittka, Dominik; Banas, Bernhard; Lennartz, Laura; Putz, Franz Josef; Eidenschink, Kathrin; Beck, Sebastian; Stempfl, Thomas; Moehle, Christoph; Reichelt-Wurm, Simone; Banas, Miriam C

    2018-01-11

    Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney

  9. Retention of gene expression in porcine islets after agarose encapsulation and long-term culture

    Energy Technology Data Exchange (ETDEWEB)

    Dumpala, Pradeep R., E-mail: pdumpala@rixd.org [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States); Holdcraft, Robert W.; Martis, Prithy C.; Laramore, Melissa A. [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States); Parker, Thomas S.; Levine, Daniel M. [The Rogosin Institute, 505 East 70th Street, New York, NY 10021 (United States); Smith, Barry H. [The Rogosin Institute, 505 East 70th Street, New York, NY 10021 (United States); NewYork-Presbyterian Hospital, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021 (United States); Gazda, Lawrence S. [The Rogosin Institute – Xenia Division, 740 Birch Road, Xenia, OH 45385 (United States)

    2016-08-05

    Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. - Highlights: • Effect of agarose encapsulation and 8 week culture on porcine islets was analyzed. • Transcriptome analysis revealed no significant change in a majority (98%) of genes. • Agarose encapsulation allows for long-term culture of porcine islets. • Islet culture allows for functional and microbial testing prior to clinical use.

  10. Retention of gene expression in porcine islets after agarose encapsulation and long-term culture

    International Nuclear Information System (INIS)

    Dumpala, Pradeep R.; Holdcraft, Robert W.; Martis, Prithy C.; Laramore, Melissa A.; Parker, Thomas S.; Levine, Daniel M.; Smith, Barry H.; Gazda, Lawrence S.

    2016-01-01

    Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. - Highlights: • Effect of agarose encapsulation and 8 week culture on porcine islets was analyzed. • Transcriptome analysis revealed no significant change in a majority (98%) of genes. • Agarose encapsulation allows for long-term culture of porcine islets. • Islet culture allows for functional and microbial testing prior to clinical use.

  11. Improving the physical health in long-term psychiatric inpatients

    DEFF Research Database (Denmark)

    Hjorth, Peter; Davidsen, A.S.; Killian, R.

    2014-01-01

    programme to improve physical health is effective. METHODS: An extension of the European Network for Promoting the Health of Residents in Psychiatric and Social Care Institutions (HELPS) project further developed as a 12-month controlled cluster-randomized intervention study in the Danish centre. Waist......, but not significant, reduction in waist circumference, while participants in the control group showed a significant increase in waist circumference. CONCLUSIONS: The intervention had a positive effect on the physical health of the patients measured by a reduction in the increase of waist circumference....

  12. Splenectomy Does Not Improve Long-Term Outcome After Stroke.

    Science.gov (United States)

    Zierath, Dannielle; Shen, Angela; Stults, Astiana; Olmstead, Theresa; Becker, Kyra J

    2017-02-01

    Immune responses to brain antigens after stroke contribute to poor outcome. We hypothesized that splenectomy would lessen the development of such responses and improve outcome. Male Lewis rats (275-350 g) underwent 2-hour middle cerebral artery occlusion immediately after splenectomy or sham splenectomy. Animals were survived to 4 weeks (672 hrs), and immune responses to myelin basic protein determined at euthanasia. Infarct volume was determined in a subset of animals euthanized at 72 hours. Behavioral outcomes were assessed to 672 hours. Splenectomy was associated with worse neurological scores early after stroke, but infarct size at 72 hours was similar in both groups. Behavioral outcomes and immune responses to myelin basic protein were also similar among splenectomized and sham-operated animals 672 hours after middle cerebral artery occlusion. Splenectomy did not alter the immune responses to brain antigens or improve outcome after stroke. Differences between this study and other studies of splenectomy and stroke are examined. © 2017 American Heart Association, Inc.

  13. Long-Term Heating to Improve Receiver Performance

    Energy Technology Data Exchange (ETDEWEB)

    Glatzmaier, Greg C.; Cable, Robert; Newmarker, Marc

    2017-06-27

    The buildup of hydrogen in the heat transfer fluid (HTF) that circulates through components of parabolic trough power plants decreases receiver thermal efficiency, and ultimately, it decreases plant performance and electricity output. The generation and occurrence of hydrogen in the HTF provides the driving force for hydrogen to permeate from the HTF through the absorber tube wall and into the receiver annulus. Getters adsorb hydrogen from the annulus volume until they saturate and are no longer able to maintain low hydrogen pressure. The increase in hydrogen pressure within the annulus significantly degrades thermal performance of the receiver and decreases overall power-plant efficiency. NREL and Acciona Energy North America (Acciona) are developing a method to control the levels of dissolved hydrogen in the circulating HTF. The basic approach is to remove hydrogen from the expansion tanks of the HTF subsystem at a rate that maintains hydrogen in the circulating HTF to a target level. Full-plant steady-state models developed by the National Renewable Energy Laboratory (NREL) predict that if hydrogen is removed from the HTF within the expansion tanks, the HTF that circulates through the collector field remains essentially free of hydrogen until the HTF returns to the power block in the hot headers. One of the key findings of our modeling is the prediction that hydrogen will reverse-permeate out of the receiver annulus if dissolved hydrogen in the HTF is kept sufficiently low. To test this prediction, we performed extended heating of an in-service receiver that initially had high levels of hydrogen in its annulus. The heating was performed using NREL's receiver test stand. Results of our testing showed that receiver heat loss steadily decreased with daily heating, resulting in a corresponding improvement in receiver thermal efficiency.

  14. Improvement of Regulatory Framework for Long-Term Operation and Ageing Management of NPPs

    International Nuclear Information System (INIS)

    Kostenko, S.P.

    2015-01-01

    The regulatory framework for long-term operation and ageing management of NPP units in Ukraine was reviewed and deficiencies were identified. The procedure for improving regulatory framework for long-term operation and ageing management is presented. It takes into consideration IAEA recommendations and international practices, as well as experience obtained in long-term operation efforts for Rivne NPP-1, 2 and South Ukraine NPP-1. The paper demonstrates interrelations between standards and technical documents on long-term operation and ageing management. The information is presented regarding the current state of regulatory and legal documentation development and industry-specific standards on long-term operation and ageing management of NPP units in Ukraine

  15. Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Y.; Li, Y.P.; He, F.; Liu, X.Q.; Zhang, J.Y. [Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

    2015-04-28

    Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34{sup +} monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34{sup +} endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells.

  16. Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

    Science.gov (United States)

    Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

    2007-01-01

    The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

  17. Ways how to express the Value of Long-term Assets

    OpenAIRE

    Tomášková, Pavlína

    2008-01-01

    The goal of this study is to analyze the current methods of expression the Value of Long-term Assets. The captures are in such order that after the explanation of basic terms there is application of the Measurment methods to different types of Assets, like tangible or intangible assets.

  18. Synaptic Transmission Optimization Predicts Expression Loci of Long-Term Plasticity.

    Science.gov (United States)

    Costa, Rui Ponte; Padamsey, Zahid; D'Amour, James A; Emptage, Nigel J; Froemke, Robert C; Vogels, Tim P

    2017-09-27

    Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression-pre- or postsynaptic-is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism

    DEFF Research Database (Denmark)

    Alfieri, A; Martone, D; Randers, Morten Bredsgaard

    2015-01-01

    and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM...... to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males....... are directly or indirectly involved in the glucose and lipid oxidative metabolism. Multiple linear regression analysis revealed that fat percentage was independently associated with NAMPT, PPARγ and adiponectin expression. In conclusion, long-term recreational football training could be a useful tool...

  20. U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats

    DEFF Research Database (Denmark)

    Ahnstedt, Hilda; Mostajeran, Maryam; Blixt, Frank W

    2015-01-01

    , responses to this treatment in females and long-term effects on outcome are not known. Initial experiments used in vitro organ culture of cerebral arteries, confirming ERK1/2 activation and increased ETB receptor-mediated vasoconstriction in female cerebral arteries. Transient middle cerebral artery......-mediated contraction was studied with myograph and protein expression with immunohistochemistry. In vitro organ culture and tMCAO resulted in vascular ETB receptor upregulation and activation of ERK1/2 that was prevented by U0126. Although no effect on infarct size, U0126 improved the long-term neurologic function...

  1. Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation.

    Science.gov (United States)

    Larrosa, Pablo Nicolás Fernández; Ojea, Alejandro; Ojea, Ignacio; Molina, Victor Alejandro; Zorrilla-Zubilete, María Aurelia; Delorenzi, Alejandro

    2017-07-01

    Acute stress impairs memory retrieval of several types of memories. An increase in glucocorticoids, several minutes after stressful events, is described as essential to the impairing retrieval-effects of stressors. Moreover, memory retrieval under stress can have long-term consequences. Through what process does the reactivated memory under stress, despite the disrupting retrieval effects, modify long-term memories? The reconsolidation hypothesis proposes that a previously consolidated memory reactivated by a reminder enters a vulnerability phase (labilization) during which it is transiently sensitive to modulation, followed by a re-stabilization phase. However, previous studies show that the expression of memories during reminder sessions is not a condition to trigger the reconsolidation process since unexpressed memories can be reactivated and labilized. Here we evaluate whether it is possible to reactivate-labilize a memory under the impairing-effects of a mild stressor. We used a paradigm of human declarative memory whose reminder structure allows us to differentiate between a reactivated-labile memory state and a reactivated but non-labile state. Subjects memorized a list of five cue-syllables associated with their respective response-syllables. Seventy-two hours later, results showed that the retrieval of the paired-associate memory was impaired when tested 20min after a mild stressor (cold pressor stress (CPS)) administration, coincident with cortisol levels increase. Then, we investigated the long-term effects of CPS administration prior to the reminder session. Under conditions where the reminder initiates the reconsolidation process, CPS impaired the long-term memory expression tested 24h later. In contrast, CPS did not show effects when administered before a reminder session that does not trigger reconsolidation. Results showed that memory reactivation-labilization occurs even when retrieval was impaired. Memory reactivation under stress could hinder

  2. Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

    Directory of Open Access Journals (Sweden)

    Antonio Costantini

    2016-01-01

    Full Text Available Myotonic dystrophy type 1, also known as Steinert′s disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1 is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC, the Muscular Impairment Rating Scale (MIRS, and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients′ activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively. The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

  3. Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

    Science.gov (United States)

    Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

    2016-09-01

    Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients' activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

  4. Human Albumin Improves Long-Term Behavioral Sequelae After Subarachnoid Hemorrhage Through Neurovascular Remodeling.

    Science.gov (United States)

    Xie, Yi; Liu, Wenhua; Zhang, Xiaohao; Wang, Liumin; Xu, Lili; Xiong, Yunyun; Yang, Lian; Sang, Hongfei; Ye, Ruidong; Liu, Xinfeng

    2015-10-01

    Subarachnoid hemorrhage results in significant long-lasting neurologic sequelae. Here, we investigated whether human albumin improves long-term outcomes in experimental subarachnoid hemorrhage and whether neurovascular remodeling is involved in the protection of albumin. Laboratory investigation. Hospital research laboratory. Male Sprague-Dawley rats. Rats underwent subarachnoid hemorrhage by endovascular perforation. Albumin of either 0.63 or 1.25 g/kg was injected IV immediately after the surgery. Modified Garcia test, beam-walking test, novel object recognition, and Morris water maze were employed to determine the behavioral deficits. The effects of albumin on early neurovascular dysfunction and chronic synaptic plasticity were also studied. Both doses of albumin significantly improved the sensorimotor scores (F = 31.277; p = 0.001) and cognitive performance (F = 7.982; p = 0.001 in novel object recognition test; and F = 3.431; p = 0.026 in the latency analysis of Morris water maze test) for at least 40 days after subarachnoid hemorrhage. There were remarkable microvasculature hypoperfusion, intracranial pressure rise, early vasoconstriction, neural apoptosis, and degeneration in subarachnoid hemorrhage rats, with albumin significantly attenuating such neurovascular dysfunction. Furthermore, albumin markedly prevented blood-brain barrier disruption, as indicated by less blood-brain barrier leakage, preserved blood-brain barrier-related proteins, and dampened gelatinase activities. The expressions of key synaptic elements were up-regulated with albumin supplementation in both acute and chronic phases. Accordingly, a higher dendritic spine density was observed in the prefrontal and hippocampal areas of albumin-treated subarachnoid hemorrhage animals. Albumin at low-to-moderate doses markedly improves long-term neurobehavioral sequelae after subarachnoid hemorrhage, which may involve an integrated process of neurovascular remodeling.

  5. Differential Gene Expression Profiling of Enriched Human Spermatogonia after Short- and Long-Term Culture

    Directory of Open Access Journals (Sweden)

    Sabine Conrad

    2014-01-01

    Full Text Available This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks and long-term culture (up to more than 14 months in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+ matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future.

  6. The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia

    Science.gov (United States)

    Liu, Rong-Yu; Cleary, Leonard J.; Byrne, John H.

    2011-01-01

    Accumulating evidence suggests that the transcriptional activator CREB1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover, creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference (RNAi) techniques in sensorimotor co-cultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 h and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time in order to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE. PMID:21543617

  7. Prediction method of long-term reliability in improving residual stresses by means of surface finishing

    International Nuclear Information System (INIS)

    Sera, Takehiko; Hirano, Shinro; Chigusa, Naoki; Okano, Shigetaka; Saida, Kazuyoshi; Mochizuki, Masahito; Nishimoto, Kazutoshi

    2012-01-01

    Surface finishing methods, such as Water Jet Peening (WJP), have been applied to welds in some major components of nuclear power plants as a counter measure to Primary Water Stress Corrosion Cracking (PWSCC). In addition, the methods of surface finishing (buffing treatment) is being standardized, and thus the buffing treatment has been also recognized as the well-established method of improving stress. On the other hand, the long-term stability of peening techniques has been confirmed by accelerated test. However, the effectiveness of stress improvement by surface treatment is limited to thin layers and the effect of complicated residual stress distribution in the weld metal beneath the surface is not strictly taken into account for long-term stability. This paper, therefore, describes the accelerated tests, which confirmed that the long-term stability of the layer subjected to buffing treatment was equal to that subjected to WJP. The long-term reliability of very thin stress improved layer was also confirmed through a trial evaluation by thermal elastic-plastic creep analysis, even if the effect of complicated residual stress distribution in the weld metal was excessively taken into account. Considering the above findings, an approach is proposed for constructing the prediction method of the long-term reliability of stress improvement by surface finishing. (author)

  8. Interventions to improve long-term weight loss in patients following bariatric surgery: challenges and solutions

    Directory of Open Access Journals (Sweden)

    McGrice M

    2015-06-01

    Full Text Available Melanie McGrice, Kathlene Don Paul Nutrition Plus Enterprises, Melbourne, VIC, Australia Abstract: Bariatric surgery aims to provide long-term weight loss and improvement in weight-related comorbidities. Unfortunately, some patients do not achieve predicted weight loss targets and many regain a portion of their lost weight within 2–10 years postsurgery. A review of the literature found that behavioral, dietary, psychological, physical, and medical considerations can all play a role in suboptimal long-term weight loss. Recommendations to optimize long-term weight loss include ensuring that the patient understands how the procedure works, preoperative and postoperative education sessions, tailored nutritional supplements, restraint with liquid kilojoules, pureed foods, grazing and eating out of the home, an average of 60 minutes of physical activity per day, and lifelong annual medical, psychological, and dietary assessments.Keywords: weight, bariatric, surgery

  9. Intrathecal injection of naked plasmid DNA provides long-term expression of secreted proteins.

    Science.gov (United States)

    Hughes, Travis S; Langer, Stephen J; Johnson, Kirk W; Chavez, Raymond A; Watkins, Linda R; Milligan, Erin D; Leinwand, Leslie A

    2009-01-01

    Therapeutic benefit has been reported to result from intrathecal (i.t.) injection of transgene vectors, including naked DNA. However, most studies using naked DNA have measured only the transgene expression of intracellular proteins. Here we demonstrate that i.t. injection of naked DNA can result in long-term expression of secreted proteins. Plasmids expressing either secreted alkaline phosphatase (SEAP) or human interleukin-10 (hIL-10) were injected into the i.t. space in rats, and transgene products were repeatedly measured in the cerebrospinal fluid (CSF). Both SEAP and hIL-10 were maximal at 1 and 2 days after the injection and still detectable at 4 months. The utilization of a plasmid having two features that are hypothesized to increase gene expression (matrix attachment regions (MARs) and lack of CpG dinucleotides) resulted in a significant increase in gene expression. Reinjection of SEAP or hIL-10 plasmids after 4 months significantly increased protein levels at 1 and 14 days after the reinjection. SEAP was uniformly distributed between the DNA delivery site (approximately vertebral level T13) and the lumbar puncture site (L5/L6 inter-vertebral space), was reduced at the cisterna magna, and was detectable, though at much lower levels, in serum. These data suggest that naked DNA has the potential to be used as a therapeutic tool for applications that require long-term release of transgenes into the CSF.

  10. The Mediating Role of Insight for Long-Term Improvements in Psychodynamic Therapy

    Science.gov (United States)

    Johansson, Paul; Hoglend, Per; Ulberg, Randi; Amlo, Svein; Marble, Alice; Bogwald, Kjell-Petter; Sorbye, Oystein; Sjaastad, Mary Cosgrove; Heyerdahl, Oscar

    2010-01-01

    Objective: According to psychoanalytic theory, interpretation of transference leads to increased insight that again leads to improved interpersonal functioning over time. In this study, we performed a full mediational analysis to test whether insight gained during treatment mediates the long-term effects of transference interpretation in dynamic…

  11. Improved long-term outcomes after resection of pancreatic adenocarcinoma: a comparison between two time periods.

    Science.gov (United States)

    Serrano, Pablo E; Cleary, Sean P; Dhani, Neesha; Kim, Peter T W; Greig, Paul D; Leung, Kenneth; Moulton, Carol-Anne; Gallinger, Steven; Wei, Alice C

    2015-04-01

    Despite reduced perioperative mortality and routine use of adjuvant therapy following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), improvement in long-term outcome has been difficult to ascertain. This study compares outcomes in patients undergoing resection for PDAC within a single, high-volume academic institution over two sequential time periods. Retrospective review of patients with resected PDAC, in two cohorts: period 1 (P1), 1991-2000; and period 2 (P2), 2001-2010. Univariate and multivariate analyses using the Cox proportional hazards model were performed to determine prognostic factors associated with long-term survival. Survival was evaluated using Kaplan-Meier analyses. A total of 179 pancreatectomies were performed during P1 and 310 during P2. Perioperative mortality was 6.7 % (12/179) in P1 and 1.6 % (5/310) in P2 (p = 0.003). P2 had a greater number of lymph nodes resected (17 [0-50] vs. 7 [0-31]; p P2 (p P2 (p < 0.001). Factors associated with improved long-term survival remain comparable over time. Short- and long-term survival for patients with resected PDAC has improved over time due to decreased perioperative mortality and increased use of adjuvant therapy, although the proportion of 5-year survivors remains small.

  12. Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship.

    Science.gov (United States)

    Yoshimura, Natsue; Horiuchi, Daisuke; Shibata, Masao; Saitoe, Minoru; Qi, Mei-Ling; Okazawa, Hitoshi

    2006-04-17

    Frame shift mutations of the polyglutamine binding protein-1 (PQBP1) gene lead to total or partial truncation of the C-terminal domain (CTD) and cause mental retardation in human patients. Interestingly, normal Drosophila homologue of PQBP-1 lacks CTD. As a model to analyze the molecular network of PQBP-1 affecting intelligence, we generated transgenic flies expressing human PQBP-1 with CTD. Pavlovian olfactory conditioning revealed that the transgenic flies showed disturbance of long-term memory. In addition, they showed abnormal courtship that male flies follow male flies. Abnormal functions of PQBP-1 or its binding partner might be linked to these symptoms.

  13. c-Fos expression predicts long-term social memory retrieval in mice.

    Science.gov (United States)

    Lüscher Dias, Thomaz; Fernandes Golino, Hudson; Moura de Oliveira, Vinícius Elias; Dutra Moraes, Márcio Flávio; Schenatto Pereira, Grace

    2016-10-15

    The way the rodent brain generally processes socially relevant information is rather well understood. How social information is stored into long-term social memory, however, is still under debate. Here, brain c-Fos expression was measured after adult mice were exposed to familiar or novel juveniles and expression was compared in several memory and socially relevant brain areas. Machine Learning algorithm Random Forest was then used to predict the social interaction category of adult mice based on c-Fos expression in these areas. Interaction with a familiar co-specific altered brain activation in the olfactory bulb, amygdala, hippocampus, lateral septum and medial prefrontal cortex. Remarkably, Random Forest was able to predict interaction with a familiar juvenile with 100% accuracy. Activity in the olfactory bulb, amygdala, hippocampus and the medial prefrontal cortex were crucial to this prediction. From our results, we suggest long-term social memory depends on initial social olfactory processing in the medial amygdala and its output connections synergistically with non-social contextual integration by the hippocampus and medial prefrontal cortex top-down modulation of primary olfactory structures. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A time-course study of long term over-expression of ARR19 in mice

    Science.gov (United States)

    Qamar, Imteyaz; Ahmad, Mohammad Faiz; Narayanasamy, Arul

    2015-01-01

    A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time-course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate. PMID:26260329

  15. Improving the long-term sustainability of health aid: are Global Health Partnerships leading the way?

    Science.gov (United States)

    Dodd, Rebecca; Lane, Christopher

    2010-09-01

    Over the last decade development assistance for health has more than doubled. This increase provides an unprecedented opportunity to scale up health services, and in doing so, achieve the health Millennium Development Goals. However, sustaining scaling up will in turn require sustainable donor support until domestic health financing can substitute for it. The provision of long-term predictable finance is of particular concern in health because the bulk of costs are recurrent and many interventions require sustained, multi-year support to be successful. This is also true for health systems strengthening efforts. As the bulk of new aid resources flow through Global Health Partnerships (GHPs), their ability to make long-term commitments is critical to health systems development. In order to better understand the constraints that prevent development partners from making long-term commitments of health aid, the World Health Organization reviewed the practices of seven major health partners in committing development assistance funds over the long term. The review found increasing evidence of long-term commitments of aid for health in each of the seven agencies. The GHPs and their funders have been at the forefront of this trend, pioneering many of the new approaches. The study concludes that all partners have scope to improve the duration of aid within existing rules and regulations, and that the main constraints to doing so are political. Predictability is even more of a concern in current global economic circumstances, as access to resources begins to be squeezed. In this context it is important that we learn from GHPs, which have successfully tested innovative approaches to both raising and disbursing health funds. The prospects for change associated with the new administration in the United States-the largest health donor and the most unpredictable, but also a major supporter of GHPs-make this task even more urgent.

  16. Nursing unit leaders' influence on the long-term sustainability of evidence-based practice improvements.

    Science.gov (United States)

    Fleiszer, Andrea R; Semenic, Sonia E; Ritchie, Judith A; Richer, Marie-Claire; Denis, Jean-Louis

    2016-04-01

    To describe how actions of nursing unit leaders influenced the long-term sustainability of a best practice guidelines (BPG) program on inpatient units. Several factors influence the initial implementation of evidence-based practice improvements in nursing, with leadership recognized as essential. However, there is limited knowledge about enduring change, including how frontline nursing leaders influence the sustainability of practice improvements over the long term. A qualitative descriptive case study included 39 in-depth interviews, observations, and document reviews. Four embedded nursing unit subcases had differing levels of program sustainability at 7 years (average) following implementation. Higher levels of BPG sustainability occurred on units where formal leadership teams used an integrated set of strategies and activities. Two key strategies were maintaining priorities and reinforcing expectations. The coordinated use of six activities (e.g., discussing, evaluating, integrating) promoted the continuation of BPG practices among staff. These leadership processes, fostering exchange and learning, contributed to sustainability-promoting environments characterized by teamwork and accountability. Unit leaders are required to strategically orchestrate several overlapping and synergistic efforts to achieve long-term sustainability of BPG-based practice improvements. As part of managing overall unit performance, unit leaders may influence practice improvement sustainability by aligning vision, strategies, and activities. © 2015 John Wiley & Sons Ltd.

  17. Long-Term Quality of Life Improvement in Subjects with Healed Erosive Esophagitis: Treatment with Lansoprazole

    Science.gov (United States)

    Freston, James W.; Haber, Marian M.; Atkinson, Stuart; Hunt, Barbara; Peura, David A.

    2009-01-01

    Background Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited. Aims To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE. Methods Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months. Results During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P ≤ 0.05) greater improvements than ranitidine-treated patients in the frequency, severity, and ‘bothersomeness’ of heartburn, the symptom index, problems of activity limitation, eating and drinking problems, symptom problems, health distress, and social functioning. During dose-titrated, open-label treatment (n = 195), all disease-specific QOL scales except sleep improved significantly (P lansoprazole for 12 months in healed EE subjects produced significantly greater improvements in QOL indicators than ranitidine. These improvements were sustained during dose-titrated, open-label lansoprazole treatment. PMID:19582579

  18. Non-ablative fractional laser provides long-term improvement of mature burn scars

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth H; Danielsen, Patricia L; Paulsen, Ida F

    2015-01-01

    BACKGROUND AND OBJECTIVES: Non-ablative fractional laser-treatment is evolving for burn scars. The objective of this study was to evaluate clinical and histological long-term outcome of 1,540 nm fractional Erbium: Glass laser, targeting superficial, and deep components of mature burn scars....... MATERIALS & METHODS: Side-by-side scar-areas were randomized to untreated control or three monthly non-ablative fractional laser-treatments using superficial and extra-deep handpieces. Patient follow-up were at 1, 3, and 6 months. Primary outcome was improvement in overall scar-appearance on a modified...... of scar-appearance. CONCLUSIONS: Combined superficial and deep non-ablative fractional laser-treatments induce long-term clinical and histological improvement of mature burn scars....

  19. Perspectives for hydropower stations in Switzerland: long-term competitiveness and possibilities for improvement

    International Nuclear Information System (INIS)

    Filippini, M.; Banfi, S.; Luchsinger, C.; Wild, J.; Balmer, M.; Grand, D.; Henkels, L.; Semadeni, M.; Gnansounou, E.

    2001-01-01

    This first general study - which has the character of a preliminary study - examines the questions if the liberalisation of the electricity market will have a negative effect on the competitiveness of hydropower in the long-term and what measures can be taken against such effects. Long-term competitiveness is defined as the ability of a business in this sector to make investments in renewal in the long-term, i.e. after its concessions have expired. The three main aims of the study are: 1. Assessment of the long-term competitiveness of the sector and identification of the factors which could either have a negative effect on it or improve it, 2. Analysis of cost structures and presentation of measures through which the long-term competitiveness of the sector can be reinforced, 3. Presentation of possible political measures to be taken in this business area in order to improve the long-term competitiveness of hydropower stations. The study identifies the most important factors that determine future competitiveness as being the market prices for electricity and capital costs (depreciation and interest on own and borrowed capital). Further, water fees, taxes and regulations concerning residual water flow can be of great importance for investment decisions, in particular for those enterprises that operate close to their profitability limits. The results of the analysis indicate that, in the future, a considerable number of enterprises must be reckoned with that will refrain from renewing their plant. Such outcomes depend, of course, on developments in electricity market prices, specific investment costs, rates of interest and other economic, political, and legal conditions. Making a prognosis about the development of such parameters is linked with a high degree of uncertainty. By means of sensitivity calculations and the definition of various scenarios, attempts are made to take these uncertainties into account . Finally, the study makes reference to the fact that

  20. Long-term oxytocin administration improves social behaviors in a girl with autistic disorder.

    Science.gov (United States)

    Kosaka, Hirotaka; Munesue, Toshio; Ishitobi, Makoto; Asano, Mizuki; Omori, Masao; Sato, Makoto; Tomoda, Akemi; Wada, Yuji

    2012-08-13

    Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.

  1. Density-dependent microbial turnover improves soil carbon model predictions of long-term litter manipulations

    Science.gov (United States)

    Georgiou, Katerina; Abramoff, Rose; Harte, John; Riley, William; Torn, Margaret

    2017-04-01

    Climatic, atmospheric, and land-use changes all have the potential to alter soil microbial activity via abiotic effects on soil or mediated by changes in plant inputs. Recently, many promising microbial models of soil organic carbon (SOC) decomposition have been proposed to advance understanding and prediction of climate and carbon (C) feedbacks. Most of these models, however, exhibit unrealistic oscillatory behavior and SOC insensitivity to long-term changes in C inputs. Here we diagnose the sources of instability in four models that span the range of complexity of these recent microbial models, by sequentially adding complexity to a simple model to include microbial physiology, a mineral sorption isotherm, and enzyme dynamics. We propose a formulation that introduces density-dependence of microbial turnover, which acts to limit population sizes and reduce oscillations. We compare these models to results from 24 long-term C-input field manipulations, including the Detritus Input and Removal Treatment (DIRT) experiments, to show that there are clear metrics that can be used to distinguish and validate the inherent dynamics of each model structure. We find that widely used first-order models and microbial models without density-dependence cannot readily capture the range of long-term responses observed across the DIRT experiments as a direct consequence of their model structures. The proposed formulation improves predictions of long-term C-input changes, and implies greater SOC storage associated with CO2-fertilization-driven increases in C inputs over the coming century compared to common microbial models. Finally, we discuss our findings in the context of improving microbial model behavior for inclusion in Earth System Models.

  2. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852

  3. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity.

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows.

  4. SOIL AGROCHEMICAL PROPERTIES IMPROVEMENT IN LONG TERM FIELD EXPERIMENT WITH FERTILIZERS

    Directory of Open Access Journals (Sweden)

    Mihaela Lungu

    2005-10-01

    Full Text Available Soil fertility is studied in long-term field experiments. Researches are carried out in several agricultural research stations, out of which the following have been chosen for the present paper: Albic Luvisol* at Albota; Haplic Phaeozem at Fundulea; Chromic Luvisol at Şimnic; Calcic Chernozem at Secuieni; and Haplic Chernozem at Podu Iloaiei. Long term fertilization with nitrogen and phosphorus generally improved the soil agrochemical properties. The evolution of organic matter, nitrogen, mobile phosphorus and potassium, and mobile microelements contents were studied, using the standardized method used in the ICPA laboratories. The organic matter and total nitrogen contents didn’t change significantly under the nitrogen and phosphorus long-term fertilization influence. The mobile phosphorus contents have the tendency to grow very significantly with the growth of phosphorus fertilizers. At the same time, slight depletions of these contents are registered as the high nitrogen doses from fertilizers stimulate plant growth and, obviously, nutritive elements absorption. Mobile potassium contents changes very little, with insignificant differences. Significant depletions are registered only with high fertilizers doses, due to the stimulation of the nutritive elements absorption in plants. Microelements contents don’t change almost at all. They are within the normal content limits and no excess or deficiency was registered, in any of the studied stations. For the agricultural practice, economical studies are recommended, about how high fertilizing expenses are covered by the yield growth. Not the least, production quality study in different variants of mineral fertilization could prove interesting.

  5. Long-term musical training may improve different forms of visual attention ability.

    Science.gov (United States)

    Rodrigues, Ana Carolina; Loureiro, Maurício Alves; Caramelli, Paulo

    2013-08-01

    Many studies have suggested that structural and functional cerebral neuroplastic processes result from long-term musical training, which in turn may produce cognitive differences between musicians and non-musicians. We aimed to investigate whether intensive, long-term musical practice is associated with improvements in three different forms of visual attention ability: selective, divided and sustained attention. Musicians from symphony orchestras (n=38) and non-musicians (n=38), who were comparable in age, gender and education, were submitted to three neuropsychological tests, measuring reaction time and accuracy. Musicians showed better performance relative to non-musicians on four variables of the three visual attention tests, and such an advantage could not solely be explained by better sensorimotor integration. Moreover, in the group of musicians, significant correlations were observed between the age at the commencement of musical studies and reaction time in all visual attention tests. The results suggest that musicians present augmented ability in different forms of visual attention, thus illustrating the possible cognitive benefits of long-term musical training. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Shifting the Paradigm for Long Term Monitoring at Legacy Sites to Improve Performance while Reducing Cost

    International Nuclear Information System (INIS)

    Eddy-Dilek, Carol A.; Looney, Brian B.; Seaman, John; Kmetz, Thomas

    2013-01-01

    A major issue facing many government and private industry sites that were previously contaminated with radioactive and chemical wastes is that often the sites cannot be cleaned up enough to permit unrestricted human access. These sites will require long-term management, in some cases indefinitely, leaving site owners with the challenge of protecting human health and environmental quality in a cost effective manner. Long-term monitoring of groundwater contamination is one of the largest projected costs in the life cycle of environmental management at the Savannah River Site (SRS), the larger DOE complex, and many large federal and private sites. Currently, most monitoring strategies are focused on laboratory measurements of contaminants measured in groundwater samples collected from wells. This approach is expensive, and provides limited and lagging information about the effectiveness of cleanup activities and the behavior of the residual contamination. Over the last twenty years, DOE and other federal agencies have made significant investments in the development of various types of sensors and strategies that would allow for remote analysis of contaminants in groundwater, but these approaches do not promise significant reductions in risk or cost. Scientists at SRS have developed a new paradigm to simultaneously improve the performance of long term monitoring systems while lowering the overall cost of monitoring. This alternative approach incorporates traditional point measurements of contaminant concentration with measurements of controlling variables including boundary conditions, master variables, and traditional plume/contaminant variables. Boundary conditions are the overall driving forces that control plume movement and therefore provide leading indication to changes in plume stability. These variables include metrics associated with meteorology, hydrology, hydrogeology, and land use. Master variables are the key variables that control the chemistry of the

  7. Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

    Science.gov (United States)

    Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

    2007-09-01

    In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

  8. Long-term Prostate-specific Antigen Velocity in Improved Classification of Prostate Cancer Risk and Mortality

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Bojesen, Stig E; Kamstrup, Pia R

    2013-01-01

    BACKGROUND: It remains unclear whether adding long-term prostate-specific antigen velocity (PSAV) to baseline PSA values improves classification of prostate cancer (PCa) risk and mortality in the general population. OBJECTIVE: To determine whether long-term PSAV improves classification of PCa risk...

  9. Mid- and long-term runoff predictions by an improved phase-space reconstruction model

    International Nuclear Information System (INIS)

    Hong, Mei; Wang, Dong; Wang, Yuankun; Zeng, Xiankui; Ge, Shanshan; Yan, Hengqian; Singh, Vijay P.

    2016-01-01

    In recent years, the phase-space reconstruction method has usually been used for mid- and long-term runoff predictions. However, the traditional phase-space reconstruction method is still needs to be improved. Using the genetic algorithm to improve the phase-space reconstruction method, a new nonlinear model of monthly runoff is constructed. The new model does not rely heavily on embedding dimensions. Recognizing that the rainfall–runoff process is complex, affected by a number of factors, more variables (e.g. temperature and rainfall) are incorporated in the model. In order to detect the possible presence of chaos in the runoff dynamics, chaotic characteristics of the model are also analyzed, which shows the model can represent the nonlinear and chaotic characteristics of the runoff. The model is tested for its forecasting performance in four types of experiments using data from six hydrological stations on the Yellow River and the Yangtze River. Results show that the medium-and long-term runoff is satisfactorily forecasted at the hydrological stations. Not only is the forecasting trend accurate, but also the mean absolute percentage error is no more than 15%. Moreover, the forecast results of wet years and dry years are both good, which means that the improved model can overcome the traditional ‘‘wet years and dry years predictability barrier,’’ to some extent. The model forecasts for different regions are all good, showing the universality of the approach. Compared with selected conceptual and empirical methods, the model exhibits greater reliability and stability in the long-term runoff prediction. Our study provides a new thinking for research on the association between the monthly runoff and other hydrological factors, and also provides a new method for the prediction of the monthly runoff. - Highlights: • The improved phase-space reconstruction model of monthly runoff is established. • Two variables (temperature and rainfall) are incorporated

  10. Mid- and long-term runoff predictions by an improved phase-space reconstruction model

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Mei [Research Center of Ocean Environment Numerical Simulation, Institute of Meteorology and oceanography, PLA University of Science and Technology, Nanjing (China); Wang, Dong, E-mail: wangdong@nju.edu.cn [Key Laboratory of Surficial Geochemistry, Ministry of Education, Department of Hydrosciences, School of Earth Sciences and Engineering, Collaborative Innovation Center of South China Sea Studies, State Key Laboratory of Pollution Control and Resource Reuse, Nanjing University, Nanjing 210093 (China); Wang, Yuankun; Zeng, Xiankui [Key Laboratory of Surficial Geochemistry, Ministry of Education, Department of Hydrosciences, School of Earth Sciences and Engineering, Collaborative Innovation Center of South China Sea Studies, State Key Laboratory of Pollution Control and Resource Reuse, Nanjing University, Nanjing 210093 (China); Ge, Shanshan; Yan, Hengqian [Research Center of Ocean Environment Numerical Simulation, Institute of Meteorology and oceanography, PLA University of Science and Technology, Nanjing (China); Singh, Vijay P. [Department of Biological and Agricultural Engineering Zachry Department of Civil Engineering, Texas A & M University, College Station, TX 77843 (United States)

    2016-07-15

    In recent years, the phase-space reconstruction method has usually been used for mid- and long-term runoff predictions. However, the traditional phase-space reconstruction method is still needs to be improved. Using the genetic algorithm to improve the phase-space reconstruction method, a new nonlinear model of monthly runoff is constructed. The new model does not rely heavily on embedding dimensions. Recognizing that the rainfall–runoff process is complex, affected by a number of factors, more variables (e.g. temperature and rainfall) are incorporated in the model. In order to detect the possible presence of chaos in the runoff dynamics, chaotic characteristics of the model are also analyzed, which shows the model can represent the nonlinear and chaotic characteristics of the runoff. The model is tested for its forecasting performance in four types of experiments using data from six hydrological stations on the Yellow River and the Yangtze River. Results show that the medium-and long-term runoff is satisfactorily forecasted at the hydrological stations. Not only is the forecasting trend accurate, but also the mean absolute percentage error is no more than 15%. Moreover, the forecast results of wet years and dry years are both good, which means that the improved model can overcome the traditional ‘‘wet years and dry years predictability barrier,’’ to some extent. The model forecasts for different regions are all good, showing the universality of the approach. Compared with selected conceptual and empirical methods, the model exhibits greater reliability and stability in the long-term runoff prediction. Our study provides a new thinking for research on the association between the monthly runoff and other hydrological factors, and also provides a new method for the prediction of the monthly runoff. - Highlights: • The improved phase-space reconstruction model of monthly runoff is established. • Two variables (temperature and rainfall) are incorporated

  11. Long-term in vitro, cell-type-specific genome-wide reprogramming of gene expression

    International Nuclear Information System (INIS)

    Hakelien, Anne-Mari; Gaustad, Kristine G.; Taranger, Christel K.; Skalhegg, Bjorn S.; Kuentziger, Thomas; Collas, Philippe

    2005-01-01

    We demonstrate a cell extract-based, genome-wide and heritable reprogramming of gene expression in vitro. Kidney epithelial 293T cells have previously been shown to take on T cell properties following a brief treatment with an extract of Jurkat T cells. We show here that 293T cells exposed for 1 h to a Jurkat cell extract undergo genome-wide, target cell-type-specific and long-lasting transcriptional changes. Microarray analyses indicate that on any given week after extract treatment, ∼2500 genes are upregulated >3-fold, of which ∼900 are also expressed in Jurkat cells. Concomitantly, ∼1500 genes are downregulated or repressed, of which ∼500 are also downregulated in Jurkat cells. Gene expression changes persist for over 30 passages (∼80 population doublings) in culture. Target cell-type specificity of these changes is shown by the lack of activation or repression of Jurkat-specific genes by extracts of 293T cells or carcinoma cells. Quantitative RT-PCR analysis confirms the long-term transcriptional activation of genes involved in key T cell functions. Additionally, growth of cells in suspended aggregates, expression of CD3 and CD28 T cell surface markers, and interleukin-2 secretion by 293T cells treated with extract of adult peripheral blood T cells illustrate a functional nuclear reprogramming. Therefore, target cell-type-specific and heritable changes in gene expression, and alterations in cell function, can be promoted by extracts derived from transformed cells as well as from adult primary cells

  12. Caffeine and diphenyl diselenide improve long-term memory impaired in middle-aged rats.

    Science.gov (United States)

    Leite, Marlon R; Marcondes Sari, Marcel Henrique; de Freitas, Mayara L; Oliveira, Lia P; Dalmolin, Laíza; Brandão, Ricardo; Zeni, Gilson

    2014-05-01

    The aim of the present study was to evaluate the effects of diphenyl diselenide (PhSe)2 supplemented diet (10ppm) associated to the administration of caffeine (15mg/kg; i.g.) for 30days on the novel object recognition memory in middle-aged rats. The present findings showed that (PhSe)2-supplemented diet enhanced short-term memory, but not long-term memory, of middle-aged rats in the novel object recognition task. The (PhSe)2 supplemented diet associated with caffeine administration improved long-term memory, but did not alter short-term memory, impaired in middle-aged rats. Daily caffeine administration to middle-aged rats had no effect on the memory tasks. Diet supplemented with (PhSe)2 plus caffeine administration increased the number of crossings and rearings reduced in middle-aged rats. Caffeine administration plus (PhSe)2 diets were effective in increasing the number of rearings and crossings, respectively, in middle-aged rats, [(3)H] glutamate uptake was reduced in hippocampal slices of rats from (PhSe)2 and caffeine plus (PhSe)2 groups. In addition, animals supplemented with (PhSe)2 showed an increase in the pCREB/CREB ratio whereas pAkt/Akt ratio was not modified. These results suggest that the effects of (PhSe)2 on the short-term memory may be related to its ability to decrease the uptake of glutamate, influencing the increase of CREB phosphorylation. (PhSe)2-supplemented diet associated to the administration of caffeine improved long-term memory impaired in middle-aged rats, an effect independent of CREB and Akt phosphorylation. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

    Directory of Open Access Journals (Sweden)

    Chunjun Sheng

    2016-01-01

    Full Text Available Type 2 diabetes (T2D is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs and functional factors with long-term caloric restriction (CR. Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.

  14. Long-term erythropoietin gene expression from transduced cells in bioisolator devices.

    Science.gov (United States)

    Yanay, Ofer; Barry, Simon C; Flint, Lisa Y; Brzezinski, Margaret; Barton, Randall W; Osborne, William R A

    2003-11-20

    Recombinant erythropoietin (EPO) is widely administered for long-term treatment of anemia associated with renal failure and other chronic diseases. The ability to deliver EPO by gene therapy would have clinical and economic benefit. We compared autologous and allogeneic transduced primary vascular smooth muscle cells for their ability to provide sustained EPO gene expression when encapsulated in TheraCyte devices implanted subcutaneously (SQ) or intraperitoneally (IP) in rats. Cells were transduced with retrovirus vector LrEpSN encoding rat EPO cDNA. Rats that received either autologous or allogeneic transduced cells showed elevated hematocrits (HCTs) ranging from 50 to 79% that were sustained for more than 12 months. The HCT of control rats remained at baseline (45.8%). Rats that received second SQ implants of either autologous or allogeneic cells showed elevations in hematocrit that were sustained for up to 12 months, suggesting the absence of immunological responses to transduced cells or implant material. All experimental groups had statistically significant elevated HCT (p TheraCyte devices was well tolerated and histological evaluation of the devices up to 12 months after surgery revealed a high degree of vascularization and no evidence of host immune response. TheraCyte devices offer a simple and safe gene delivery system that provides sustained therapeutic gene expression, permit removal and implantation of new devices, and do not require immunosuppression of the host.

  15. Sleeping Beauty-baculovirus hybrid vectors for long-term gene expression in the eye.

    Science.gov (United States)

    Turunen, Tytteli Anni Kaarina; Laakkonen, Johanna Päivikki; Alasaarela, Laura; Airenne, Kari Juhani; Ylä-Herttuala, Seppo

    2014-01-01

    A baculovirus vector is capable of efficiently transducing many nondiving and diving cell types. However, the potential of baculovirus is restricted for many gene delivery applications as a result of the transient gene expression that it mediates. The plasmid-based Sleeping Beauty (SB) transposon system integrates transgenes into target cell genome efficiently with a genomic integration pattern that is generally considered safer than the integration of many other integrating vectors; yet efficient delivery of therapeutic genes into cells of target tissues in vivo is a major challenge for nonviral gene therapy. In the present study, SB was introduced into baculovirus to obtain novel hybrid vectors that would combine the best features of the two vector systems (i.e. effective gene delivery and efficient integration into the genome), thus circumventing the major limitations of these vectors. We constructed and optimized SB-baculovirus hybrid vectors that bear either SB100x transposase or SB transposon in the forward or reverse orientations with respect to the viral backbone The functionality of the novel hybrid vectors was investigated in cell cultures and in a proof-of-concept study in the mouse eye. The hybrid vectors showed high and sustained transgene expression that remained stable and demonstrated no signs of decline during the 2 months follow-up in vitro. These results were verified in the mouse eye where persistent transgene expression was detected two months after intravitreal injection. Our results confirm that (i) SB-baculovirus hybrid vectors mediate long-term gene expression in vitro and in vivo, and (ii) the hybrid vectors are potential new tools for the treatment of ocular diseases. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Sex-Dependent and Independent Effects of Long-Term Voluntary Wheel Running on Bdnf mRNA and Protein Expression

    OpenAIRE

    Venezia, Andrew C.; Guth, Lisa M.; Sapp, Ryan M.; Spangenburg, Espen E.; Roth, Stephen M.

    2016-01-01

    The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited.

  17. Is Fibre an Effective Strategy to Improve Laxation in Long-Term Care Residents?

    Science.gov (United States)

    Dahl, Wendy J; Mendoza, Daniela Rivero

    2018-03-01

    The high prevalence of constipation in long-term care (LTC) residents has been a long-standing issue for caregivers, attending health professionals, and the residents themselves. The traditional medical response has been to utilize pharmaceutical laxatives, enemas, and suppositories for treatment. The purpose of this review was to determine if fibre supplementation (including fibre added to foods) is effective in increasing stool frequency, improving stool consistency, and decreasing laxative use in LTC residents. A systematic search was conducted using PubMed and CINAHL databases, inclusive to March 2017. Search terms included: "long-term care" or "nursing home" AND "fiber (fibre)," "bran," "psyllium," "inulin," or "prebiotic." Intervention trials of fibre supplementation with ≥5 LTC residents were included. The search generated 456 articles following removal of duplicates; 8 studies met the inclusion criteria. Three additional trials were identified through a hand search of references of pertinent articles. Current evidence suggests that added fibre may be effective in increasing stool frequency and/or decreasing laxative use in LTC residents and, thus, may lessen the burden of constipation. However, randomized controlled trials are needed to clearly demonstrate the effects of adding fibre to foods, particularly insoluble and less fermentable sources, on constipation in LTC residents.

  18. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    International Nuclear Information System (INIS)

    Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.

    2007-01-01

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion

  19. Using DCM pitch modulation and feedback to improve long term X-ray beam stability

    International Nuclear Information System (INIS)

    Bloomer, C; Dent, A; Diaz-Moreno, S; Dolbnya, I; Pedersen, U; Rehm, G; Tang, C; Thomas, C

    2013-01-01

    In this paper we demonstrate significant improvements to the stability of the monochromatic X-ray beam intensity on several beamlines at Diamond, using a modulation of the pitch axis of the DCM with a piezoelectric actuator. The modulation is detected on an intensity diagnostic (e.g. an ion chamber) using a software lock-in technique. The detected amplitude and phase are used in a feedback to keep the DCM at the peak of the rocking curve, or any arbitrary position 'off-peak' which might be desired to detune the DCM and reject unwanted harmonics. A major advantage of this software based system is the great flexibility offered, using standard, readily available instrumentation. Measurements of the short and long-term performance of the feedback on several beamlines are presented, and the limitations of such a feedback are discussed.

  20. Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

    Science.gov (United States)

    Khouri, I F; Sui, D; Jabbour, E J; Samuels, B I; Turturro, F; Alatrash, G; Anderlini, P; Ahmed, S; Oran, B; Ciurea, S O; Marin, D; Olson, A; Patel, K K; Popat, U R; Ledesma, C; Kadia, T M; Ferrajoli, A; Burger, J A; Jorgensen, J L; Medeiros, L J; Bassett, R L; Gulbis, A M

    2017-01-01

    Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

  1. Postoperative improvement in acoustic rhinometry measurements after septoplasty correlates with long-term satisfaction

    DEFF Research Database (Denmark)

    Toyserkani, N M; Frisch, Thomas; von Buchwald, Christian

    2013-01-01

    Not much is known about long-term satisfaction of septoplasty. Our goal was to compare pre- and postoperative acoustic rhinometry measurements with satisfaction 11 years after surgery.......Not much is known about long-term satisfaction of septoplasty. Our goal was to compare pre- and postoperative acoustic rhinometry measurements with satisfaction 11 years after surgery....

  2. Long-term effects of ionizing radiation on gene expression in a zebrafish model.

    Directory of Open Access Journals (Sweden)

    Lahcen Jaafar

    Full Text Available Understanding how initial radiation injury translates into long-term effects is an important problem in radiation biology. Here, we define a set of changes in the transcription profile that are associated with the long-term response to radiation exposure. The study was performed in vivo using zebrafish, an established radiobiological model organism. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose or 1.0 Gy (moderate dose of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. As a basis for comparison, 16-week old adults were exposed at the same doses and analyzed after 4 hours. Statistical analysis was performed in a way to minimize the effects of multiple comparisons. The responses to these two treatment regimes differed greatly: 360 probe sets were associated primarily with the long-term response, whereas a different 2062 probe sets were associated primarily with the response when adults of the same age were irradiated 4 hours before exposure. Surprisingly, a ten-fold difference in radiation dose (0.1 versus 1.0 Gy had little effect. Analysis at the gene and pathway level indicated that the long-term response includes the induction of cytokine and inflammatory regulators and transcription and growth factors. The acute response includes the induction of p53 target genes and modulation of the hypoxia-induced transcription factor-C/EBP axis. Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue.

  3. Improving oral hygiene in the long-term care of the elderly--a RCT.

    Science.gov (United States)

    Zenthöfer, Andreas; Dieke, Reinhard; Dieke, Anke; Wege, Karl-Christian; Rammelsberg, Peter; Hassel, Alexander J

    2013-06-01

    Oral hygiene and health of the institutionalized elderly are frequently described as inadequate. This randomized and single-blinded (outcome evaluation) study compared three types of intervention for improving oral hygiene with a control. The purpose was to investigate whether there were any significant differences between the intervention and control groups. One hundred and six participants living in long-term care homes in South-West Germany were recruited and randomly divided into four groups-three therapy groups and one control group. For all three therapy groups, teeth and dentures were cleaned professionally and individual instruction was given. One of these groups was also re-instructed and remotivated by a dentist (n = 27). One also received help from, and was remotivation by, staff educated in dental hygiene (n = 26). The third therapy group was not remotivated after professional cleaning of teeth and dentures (n = 26). For the control group, there was no intervention (n = 23). The main target clinical data were mean plaque (plaque-control record, O'Leary), gingival bleeding (Ainamo/Bay), and denture hygiene indices. For assessment of the difference between being in an intervention group and in a control group, mixed-model analysis for repeated measurements was performed for each main target variable. In addition, target clinical data were evaluated in long-term follow-up after 3 years. Compared with controls, denture hygiene, plaque, and gingival bleeding indices were significantly lower in the intervention groups over a twelve-week period (mixed model for repeated measurements; P hygiene. However, the effect decreases over time and renewal of the intervention is necessary. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Towards Improved Understanding of Drought and Drought Impacts from Long Term Earth Observation Records

    Science.gov (United States)

    Champagne, C.; Wang, S.; Liu, J.; Hadwen, T. A.

    2017-12-01

    Drought is a complex natural disaster, which often emerges slowly, but can occur at various time scales and have impacts that are not well understood. Long term observations of drought intensity and frequency are often quantified from precipitation and temperature based indices or modelled estimates of soil water storage. The maturity of satellite based observations has created the potential to enhance the understanding of drought and drought impacts, particularly in regions where traditional data sets are limited by remoteness or inaccessibility, and where drought processes are not well-quantified by models. Long term global satellite data records now provide observations of key hydrological variables, including evaporation modelled from thermal sensors, soil moisture from microwave sensors, ground water from gravity sensors and vegetation condition that can be modelled from optical sensors. This study examined trends in drought frequency, intensity and duration over diverse ecoregions in Canada, including agricultural, grassland, forested and wetland areas. Trends in drought were obtained from the Canadian Drought Monitor as well as meteorological based indices from weather stations, and evaluated against satellite derived information on evaporative stress (Anderson et al. 2011), soil moisture (Champagne et al. 2015), terrestrial water storage (Wang and Li 2016) and vegetation condition (Davidson et al. 2009). Data sets were evaluated to determine differences in how different sensors characterize the hydrology and impacts of drought events from 2003 to 2016. Preliminary results show how different hydrological observations can provide unique information that can tie causes of drought (water shortages resulting from precipitation, lack of moisture storage or evaporative stress) to impacts (vegetation condition) that hold the potential to improve the understanding and classification of drought events.

  5. Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia

    OpenAIRE

    Chen, Shanping; Cai, Diancai; Pearce, Kaycey; Sun, Philip Y-W; Roberts, Adam C; Glanzman, David L

    2014-01-01

    eLife digest Cells called neurons allow information to travel quickly around the body so that we can rapidly respond to any changes that we sense in our environment. This includes non-conscious reactions, such as the knee-jerk reflex in humans. Reflexes and other behaviors can be influenced by long-term memory, and it is thought that long-term memory is stored by changes in the synapses that connect neurons to each other. The reflexes of a sea slug known as Aplysia are often used to study mem...

  6. [Influence on glycemic control of improved diabetic gastroparesis by long-term cisapride therapy].

    Science.gov (United States)

    Ishii, K; Tanabe, S; Mitsuhashi, T; Saigenji, K

    1995-10-01

    To investigate the effect on glycemic control of improving diabetic gastroparesis, we evaluated symptoms (scored), gastric motor functions (solid and liquid gastric emptying studies and electrogastrography), and glycemic control in 11 patients with diabetic gastroparesis (5 men, 6 women, 50.4 +/- 4.5 years old) before and after treatment with cisapride (15 mg/day p.o., 12 weeks). None of the patients had organic abnormalities on gastrointestinal endoscopy. The dysmotility symptom score (maximum: 18) on cisapride significantly improved from 13.1 to 4.0 (p instant noodles labeled with 37 MBq (1 mCi) technetium-99m (both p < 0.05). Liquid gastric emptying, evaluated using a sulfamethizole technique, also improved but not significantly. Electrogastrography revealed no significant changes after treatment, but the postprandial rate of normal frequency waves tended to increase. Glycemic control was assessed based on HbA1C, fructosamine and M value. There were no significant changes in glycemic control after treatment with cisapride. We conclude that long-term administration of cisapride reduced dysmotility symptoms and improved solid and liquid gastric emptying without adversely affecting glycemic control.

  7. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    NARCIS (Netherlands)

    D. Chadha; T.D. Pache; F.J. Huikeshoven (Frans); A.O. Brinkmann (Albert); Th.H. van der Kwast (Theo)

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated

  8. Long-Term Protective Immune Response Elicited by Vaccination with an Expression Genomic Library of Toxoplasma gondii

    OpenAIRE

    Fachado, Alberto; Rodriguez, Alexandro; Molina, Judith; Silvério, Jaline C.; Marino, Ana P. M. P.; Pinto, Luzia M. O.; Angel, Sergio O.; Infante, Juan F.; Traub-Cseko, Yara; Amendoeira, Regina R.; Lannes-Vieira, Joseli

    2003-01-01

    Immunization of BALB/c mice with an expression genomic library of Toxoplasma gondii induces a Th1-type immune response, with recognition of several T. gondii proteins (21 to 117 kDa) and long-term protective immunity against a lethal challenge. These results support further investigations to achieve a multicomponent anti-T. gondii DNA vaccine.

  9. p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

    Science.gov (United States)

    Paradiso, A; Rabinovich, M; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriquez, R; Leone, B; Sapia, M G; Simone, G; De Lena, M

    1996-12-20

    In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

  10. Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.

    Science.gov (United States)

    Chen, Shanping; Cai, Diancai; Pearce, Kaycey; Sun, Philip Y-W; Roberts, Adam C; Glanzman, David L

    2014-11-17

    Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories.

  11. Improving Service Quality in Long-term Care Hospitals: National Evaluation on Long-term Care Hospitals and Employees Perception of Quality Dimensions

    OpenAIRE

    Kim, Jinkyung; Han, Woosok

    2012-01-01

    Objectives To investigate predictors for specific dimensions of service quality perceived by hospital employees in long-term care hospitals. Methods Data collected from a survey of 298 hospital employees in 18 long-term care hospitals were analysed. Multivariate ordinary least squares regression analysis with hospital fixed effects was used to determine the predictors of service quality using respondents? and organizational characteristics. Results The most significant predictors of employee-...

  12. Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer's Disease.

    Science.gov (United States)

    Pan, Xiaoli; Chen, Zhichun; Fei, Guoqiang; Pan, Shumei; Bao, Weiqi; Ren, Shuhua; Guan, Yihui; Zhong, Chunjiu

    2016-12-01

    To date, we still lack disease-modifying therapies for Alzheimer's disease (AD). Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine (300 mg daily) over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B (PiB-PET) and exhibited positive imaging with β-amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improvement as assayed by the Mini-Mental Status Examination (MMSE) with an average increase of 3.2 points at month 18 of benfotiamine administration. The three patients who received follow-up PiB-PET had a 36.7% increase in the average standardized uptake value ratio in the brain compared with that in the first scan. Importantly, the MMSE scores of these three had an average increase of 3 points during the same period. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation. Our study provides new insight to the development of disease-modifying therapy.

  13. Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

    Science.gov (United States)

    Zanin, M P; Hellström, M; Shepherd, R K; Harvey, A R; Gillespie, L N

    2014-09-26

    Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Improved local control with neoadjuvant chemotherapy for locally advanced rectal carcinoma: Long-term analysis

    International Nuclear Information System (INIS)

    Nakfoor, Bruce M.; Willett, Christopher G.; Kaufman, S. Donald; Shellito, Paul C.; Daly, William J.

    1996-01-01

    Objective: Since 1979, our institution has treated locally advanced rectal cancer with preoperative irradiation followed by resection with or without intraoperative radiation therapy (IORT). In 1986, our preoperative treatment policy was changed to include bolus 5-FU chemotherapy concurrent with irradiation in hopes of improving resectability, downstaging and/or local control rates. We report the long-term results with the addition of 5-FU chemotherapy to preoperative irradiation. Materials and Methods: From 1979 - 1994, 200 patients with locally advanced rectal carcinoma (primary or recurrent) received preoperative irradiation, resection and IORT if indicated. Bolus 5-FU (500mg/m 2 /day) chemotherapy was administered for three days during weeks one and five of irradiation. The change in treatment policy was limited to the addition of 5-FU chemotherapy: the radiation techniques (four-field), doses (50.4 Gy), and indications for intraoperative radiation (microscopic residual, gross residual, tumor adherence) remained constant. The median follow-up for the entire group of patients was 33 months (.95 months - 199 months), and the minimum follow-up was 1.5 years. Tabular results are 5-year actuarial calculations. Results: One hundred and five patients received preoperative 5-FU chemotherapy and irradiation whereas 95 patients underwent preoperative irradiation alone. Sixty-five percent of the patients were able to undergo complete resections, and 53% had transmural disease upon pathologic examination. The addition of chemotherapy did not affect the rates of resectability or tumor downstaging. However, the 10-year local control rate was significantly improved for those patients who received preoperative chemotherapy: 77% vs. 44% (p<0.01) (see figure). When stratified by extent of resection and stage, those patients who underwent complete resections or had transmural disease had significantly improved local control rates when compared to the non-chemotherapy group: No

  15. Long-Term Scheduling of Large-Scale Cascade Hydropower Stations Using Improved Differential Evolution Algorithm

    Directory of Open Access Journals (Sweden)

    Xiaohao Wen

    2018-03-01

    Full Text Available Long-term scheduling of large cascade hydropower stations (LSLCHS is a complex problem of high dimension, nonlinearity, coupling and complex constraint. In view of the above problem, we present an improved differential evolution (iLSHADE algorithm based on LSHADE, a state-of-the-art evolutionary algorithm. iLSHADE uses new mutation strategies “current to pbest/2-rand” to obtain wider search range and accelerate convergence with the preventing individual repeated failure evolution (PIRFE strategy. The handling of complicated constraints strategy of ε-constrained method is presented to handle outflow, water level and output constraints in the cascade reservoir operation. Numerical experiments of 10 benchmark functions have been done, showing that iLSHADE has stable convergence and high efficiency. Furthermore, we demonstrate the performance of the iLSHADE algorithm by comparing it with other improved differential evolution algorithms for LSLCHS in four large hydropower stations of the Jinsha River. With the applications of iLSHADE in reservoir operation, LSLCHS can obtain more power generation benefit than other alternatives in dry, normal, and wet years. The results of numerical experiments and case studies show that the iLSHADE has a distinct optimization effect and good stability, and it is a valid and reliable tool to solve LSLCHS problem.

  16. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    OpenAIRE

    Chadha, D.; Pache, T.D.; Huikeshoven, Frans; Brinkmann, Albert; Kwast, Theo

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycy...

  17. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    OpenAIRE

    Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

    2017-01-01

    AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS...

  18. Short- and long-term effects of a quality improvement collaborative on diabetes management

    Directory of Open Access Journals (Sweden)

    Niessen Louis W

    2010-11-01

    Full Text Available Abstract Introduction This study examined the short- and long-term effects of a quality improvement collaborative on patient outcomes, professional performance, and structural aspects of chronic care management of type 2 diabetes in an integrated care setting. Methods Controlled pre- and post-intervention study assessing patient outcomes (hemoglobin A1c, cholesterol, blood pressure, weight, blood lipid levels, and smoking status, professional performance (guideline adherence, and structural aspects of chronic care management from baseline up to 24 months. Analyses were based on 1,861 patients with diabetes in six intervention and nine control regions representing 37 general practices and 13 outpatient clinics. Results Modest but significant improvement was seen in mean systolic blood pressure (decrease by 4.0 mm Hg versus 1.6 mm Hg and mean high density lipoprotein levels (increase by 0.12 versus 0.03 points at two-year follow up. Positive but insignificant differences were found in hemoglobin A1c (0.3%, cholesterol, and blood lipid levels. The intervention group showed significant improvement in the percentage of patients receiving advice and instruction to examine feet, and smaller reductions in the percentage of patients receiving instruction to monitor blood glucose and visiting a dietician annually. Structural aspects of self-management and decision support also improved significantly. Conclusions At a time of heightened national attention toward diabetes care, our results demonstrate a modest benefit of participation in a multi-institutional quality improvement collaborative focusing on integrated, patient-centered care. The effects persisted for at least 12 months after the intervention was completed. Trial number http://clinicaltrials.gov Identifier: NCT 00160017

  19. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

    Science.gov (United States)

    Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

  20. Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.

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    Aline Rideau Batista Novais

    Full Text Available Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.

  1. Island-Model Genomic Selection for Long-Term Genetic Improvement of Autogamous Crops.

    Science.gov (United States)

    Yabe, Shiori; Yamasaki, Masanori; Ebana, Kaworu; Hayashi, Takeshi; Iwata, Hiroyoshi

    2016-01-01

    selection in autogamous crops, especially bringing long-term improvement.

  2. Island-Model Genomic Selection for Long-Term Genetic Improvement of Autogamous Crops.

    Directory of Open Access Journals (Sweden)

    Shiori Yabe

    potential of genomic selection in autogamous crops, especially bringing long-term improvement.

  3. Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke: A Randomized Controlled Trial.

    Science.gov (United States)

    Bunketorp-Käll, Lina; Lundgren-Nilsson, Åsa; Samuelsson, Hans; Pekny, Tulen; Blomvé, Karin; Pekna, Marcela; Pekny, Milos; Blomstrand, Christian; Nilsson, Michael

    2017-07-01

    Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke. Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants' perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up. One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79-9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00-13.66]), compared with controls (-0.5 [-3.20 to 2.28]); P =0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes. Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke. URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059. © 2017 American Heart Association, Inc.

  4. Improving long term oxidation protection for {gamma}-TiAl substrates

    Energy Technology Data Exchange (ETDEWEB)

    Bobzin, K.; Schlaefer, T.; Bruehl, M.; Linke, T.F. [Thermisches Spritzen, Institut fuer Oberflaechentechnik (IOT), RWTH Aachen University (Germany); Warda, T.

    2011-11-15

    In previous work, a thermal spray multilayer system consisting of Zirconia (ZrO{sub 2}) and MCrAlY top coat showed promising results regarding the oxidation behavior of the Gamma Titanium Aluminides substrates tested, which encouraged further research activities. Diffusion of substrate material was successfully inhibited by a ceramic Zirconia coating. A building up of a dense and stable oxide layer could be achieved by additional application of an MCrAlY top coat, leading to improved oxidation resistance and thus showing feasibility. In this work the main focus for development was put on enhancing adhesion and lowering residual stresses of the coatings in order to allow long term and cyclic testing without delamination taking place. Being a very brittle material, Gamma Titanium Aluminides require special surface treatment to enable roughening which is crucial for a strong mechanical bond between substrate and coating. Alternatives to conventional grit blasting as a standard preparation method were investigated. These were micro-abrasive blasting and blasting at elevated temperature ({approx}300-550 C) to allow a more ductile behavior. The paper will highlight the implications by means of these measures and will also show the present development status of the multilayer system. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Development and Application of Improved Long-Term Datasets of Surface Hydrology for Texas

    Directory of Open Access Journals (Sweden)

    Kyungtae Lee

    2017-01-01

    Full Text Available Freshwater availability and agricultural production are key factors for sustaining the fast growing population and economy in the state of Texas, which is the third largest state in terms of agricultural production in the United States. This paper describes a long-term (1918–2011 grid-based (1/8° surface hydrological dataset for Texas at a daily time step based on simulations from the Variable Infiltration Capacity (VIC hydrological model. The model was calibrated and validated against observed streamflow over 10 Texas river basins. The simulated soil moisture was also evaluated using in situ observations. Results suggest that there is a decreasing trend in precipitation and an increasing trend in temperature in most of the basins. Droughts and floods were reconstructed and analyzed. In particular, the spatially distributed severity and duration of major Texas droughts were compared to identify new characteristics. The modeled flood recurrence interval and the return period were also compared with observations. Results suggest the performance of extreme flood simulations needs further improvement. This dataset is expected to serve as a benchmark which may contribute to water resources management and to mitigating agricultural drought, especially in the context of understanding the effects of climate change on crop yield in Texas.

  6. The Responsive Leadership Intervention: Improving leadership and individualized care in long-term care.

    Science.gov (United States)

    Caspar, Sienna; Le, Anne; McGilton, Katherine S

    The Responsive Leadership Intervention (RLI) is a multi-faceted intervention. We evaluated the influence of the RLI on i) responsive leadership practices by team leaders; ii) health care aides' (HCAs) self-determination; iii) HCAs' perceived ability to provide individualized care. A quasi-experimental repeated measures non-equivalent control group design was used to assess participant outcomes in four long-term care facilities (two control, two intervention) across four time periods. Change from baseline to 1-month post-intervention was greater in the intervention group than control group for Individualized Care (IC) (p = 0.001), but not for Self Determination (p = 0.26). Perceived levels of responsive leadership was greater following the intervention among participants with baseline measures that were less than the median (p = 0.007), but not if greater. At 3-months post-intervention, the intervention group retained 32% of the difference from control in IC, and 49% of the difference from control in responsive leadership; at 6-months post-intervention, 35% and 28%, respectively. The RLI is a feasible method for improving responsive leadership practices and individualized care. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Improving an Integer Linear Programming Model of an Ecovat Buffer by Adding Long-Term Planning

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    Gijs J. H. de Goeijen

    2017-12-01

    Full Text Available The Ecovat is a seasonal thermal storage solution consisting of a large underground water tank divided into a number of virtual segments that can be individually charged and discharged. The goal of the Ecovat is to supply heat demand to a neighborhood throughout the entire year. In this work, we extend an integer linear programming model to describe the charging and discharging of such an Ecovat buffer by adding a long-term (yearly planning step to the model. We compare the results from the model using this extension to previously obtained results and show significant improvements when looking at the combination of costs and the energy content of the buffer at the end of the optimization. Furthermore, we show that the model is very robust against prediction errors. For this, we compare two different cases: one case in which we assume perfect predictions are available and one case in which we assume no predictions are available. The largest observed difference in costs between these two cases is less than 2%.

  8. Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel

    Directory of Open Access Journals (Sweden)

    AH Huang

    2010-02-01

    Full Text Available Mesenchymal stem cells (MSCs are an attractive cell source for cartilage tissue engineering given their ability to undergo chondrogenesis in 3D culture systems. Mechanical forces play an important role in regulating both cartilage development and MSC chondrogenic gene expression, however, mechanical stimulation has yet to enhance the mechanical properties of engineered constructs. In this study, we applied long-term dynamic compression to MSC-seeded constructs and assessed whether varying pre-culture duration, loading regimens and inclusion of TGF-beta3 during loading would influence functional outcomes and these phenotypic transitions. Loading initiated before chondrogenesis decreased functional maturation, although chondrogenic gene expression increased. In contrast, loading initiated after chondrogenesis and matrix elaboration further improved the mechanical properties of MSC-based constructs, but only when TGF-beta3 levels were maintained and under specific loading parameters. Although matrix quantity was not affected by dynamic compression, matrix distribution, assessed histologically and by FT-IRIS analysis, was significantly improved on the micro- (pericellular and macro- (construct expanse scales. Further, whole genome expression profiling revealed marked shifts in the molecular topography with dynamic loading. These results demonstrate, for the first time, that dynamic compressive loading initiated after a sufficient period of chondro-induction and with sustained TGF-beta exposure enhances matrix distribution and the mechanical properties of MSC-seeded constructs.

  9. Trinity of Quality Improvement : Studies on structure, process and outcome related to quality improvement in long-term care in the Netherlands between 2007 and 2011

    NARCIS (Netherlands)

    A.C.M. Winters-van der Meer (Sjenny)

    2014-01-01

    markdownabstract__Abstract__ This thesis discusses quality improvement in long-term care organisations in the Netherlands. It explores the influencing factors on quality improvement and aims at identifying opportunities for long-term care organisations to ‘improve their improvement’. This

  10. Utilización de la toxina botulínica para mejorar la funcionalidad y la expresión del labio en parálisis facial de larga evolución Use of botulinum toxin to improve the functionality and expression of the lip in long-term facial palsy

    Directory of Open Access Journals (Sweden)

    C. Gómez Martín

    2010-06-01

    Full Text Available La parálisis de la rama marginal del nervio facial en el contexto de una parálisis facial de larga evolución, produce una deformidad estética y funcional que puede ser mejorada con la inyección de toxina botulínica. Utilizamos esta técnica en 2 pacientes consiguiendo unos resultados casi inmediatos en lo que se refiere a la apertura bucal, a la expresión y a la continencia oral. Indicamos esta técnica en pacientes de edad avanzada, con múltiples operaciones previas y que aceptan este procedimiento no invasivo para mejorar su autoestima y su calidad de vida.Paralysis of the marginal branch of the facial nerve in the context of a long-term facial paralysis, produces an aesthetic and functional deformity that can be improved with botulinum toxin injection. We use this technique in 2 patients who achieved almost immediate results in terms of oral opening, oral expression and continence. Botulinum toxin injection can be used in elderly patients with multiple previous operations who accept this non-invasive procedure, improving their selfesteem and their quality of life.

  11. Long-term degradation (or improvement?) of cementitious grout/concrete for waste disposal at Hanford

    International Nuclear Information System (INIS)

    Piepho, M.G.

    1997-01-01

    If grout and/or concrete barriers and containments are considered for long-term (500 yrs to 100,000 ) waste disposal, then long-term degradation of grout/cement materials (and others) need to be studied. Long-term degradations of a cementitious grout monolith (15.4mW x 10.4mH x 37.6mL) and its containment concrete shell and asphalt shell (each 1-m thick) were analyzed. The main degradation process of the concrete shell was believed to be fractures due to construction joints, shrinkage, thermal stress, settlement, and seismic events. A scenario with fractures was modeled (flow and transport model) for long-term risk performance (out to a million yrs). Even though the concrete/grout is expected to fracture, the concrete/grout chemistry, which has high Ph value, is very beneficial in causing calcite deposits from calcium in the water precipitating in the fractures. These calcite deposits will tend to plug the fracture and keep water from entering. The effectiveness of such plugging needs to be studied more. It's possible that the plugged fractures are more impermeable than the original concrete/grout. The long-term performance of concrete/grout barriers will be determined by its chemistry, not its mechanical properties

  12. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

    Science.gov (United States)

    Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

    2015-03-15

    Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

  14. Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

    Science.gov (United States)

    Liao, Yueh-Hsiang; Li, Chia-Ing; Lin, Cheng-Chieh; Lin, Jaung-Geng; Chiang, Jen-Huai; Li, Tsai-Chung

    2017-12-01

    Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

  15. Noradrenergic control of gene expression and long-term neuronal adaptation evoked by learned vocalizations in songbirds.

    Directory of Open Access Journals (Sweden)

    Tarciso A F Velho

    Full Text Available Norepinephrine (NE is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain's response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM, an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express α-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local α-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, α-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.

  16. Personally tailored activities for improving psychosocial outcomes for people with dementia in long-term care.

    Science.gov (United States)

    Möhler, Ralph; Renom, Anna; Renom, Helena; Meyer, Gabriele

    2018-02-13

    People with dementia who are being cared for in long-term care settings are often not engaged in meaningful activities. Offering them activities which are tailored to their individual interests and preferences might improve their quality of life and reduce challenging behaviour. ∙ To assess the effects of personally tailored activities on psychosocial outcomes for people with dementia living in long-term care facilities.∙ To describe the components of the interventions.∙ To describe conditions which enhance the effectiveness of personally tailored activities in this setting. We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 16 June 2017 using the terms: personally tailored OR individualized OR individualised OR individual OR person-centred OR meaningful OR personhood OR involvement OR engagement OR engaging OR identity. We also performed additional searches in MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science (ISI Web of Science), ClinicalTrials.gov, and the World Health Organization (WHO) ICTRP, to ensure that the search for the review was as up to date and as comprehensive as possible. We included randomised controlled trials and controlled clinical trials offering personally tailored activities. All interventions included an assessment of the participants' present or past preferences for, or interests in, particular activities as a basis for an individual activity plan. Control groups received either usual care or an active control intervention. Two authors independently checked the articles for inclusion, extracted data and assessed the methodological quality of included studies. For all studies, we assessed the risk of selection bias, performance bias, attrition bias and detection bias. In case of missing information, we contacted the study authors. We included eight studies with 957 participants. The mean age of participants in the studies ranged from 78 to 88

  17. Improving long-term care provision: towards demand-based care by means of modularity

    Directory of Open Access Journals (Sweden)

    Meijboom Bert

    2010-09-01

    Full Text Available Abstract Background As in most fields of health care, societal and political changes encourage suppliers of long-term care to put their clients at the center of care and service provision and become more responsive towards client needs and requirements. However, the diverse, multiple and dynamic nature of demand for long-term care complicates the movement towards demand-based care provision. This paper aims to advance long-term care practice and, to that end, examines the application of modularity. This concept is recognized in a wide range of product and service settings for its ability to design demand-based products and processes. Methods Starting from the basic dimensions of modularity, we use qualitative research to explore the use and application of modularity principles in the current working practices and processes of four organizations in the field of long-term care for the elderly. In-depth semi-structured interviews were conducted with 38 key informants and triangulated with document research and observation. Data was analyzed thematically by means of coding and subsequent exploration of patterns. Data analysis was facilitated by qualitative analysis software. Results Our data suggest that a modular setup of supply is employed in the arrangement of care and service supply and assists providers of long-term care in providing their clients with choice options and variation. In addition, modularization of the needs assessment and package specification process allows the case organizations to manage client involvement but still provide customized packages of care and services. Conclusion The adequate setup of an organization's supply and its specification phase activities are indispensible for long-term care providers who aim to do better in terms of quality and efficiency. Moreover, long-term care providers could benefit from joint provision of care and services by means of modular working teams. Based upon our findings, we are able to

  18. Improving long-term care provision: towards demand-based care by means of modularity

    Science.gov (United States)

    2010-01-01

    Background As in most fields of health care, societal and political changes encourage suppliers of long-term care to put their clients at the center of care and service provision and become more responsive towards client needs and requirements. However, the diverse, multiple and dynamic nature of demand for long-term care complicates the movement towards demand-based care provision. This paper aims to advance long-term care practice and, to that end, examines the application of modularity. This concept is recognized in a wide range of product and service settings for its ability to design demand-based products and processes. Methods Starting from the basic dimensions of modularity, we use qualitative research to explore the use and application of modularity principles in the current working practices and processes of four organizations in the field of long-term care for the elderly. In-depth semi-structured interviews were conducted with 38 key informants and triangulated with document research and observation. Data was analyzed thematically by means of coding and subsequent exploration of patterns. Data analysis was facilitated by qualitative analysis software. Results Our data suggest that a modular setup of supply is employed in the arrangement of care and service supply and assists providers of long-term care in providing their clients with choice options and variation. In addition, modularization of the needs assessment and package specification process allows the case organizations to manage client involvement but still provide customized packages of care and services. Conclusion The adequate setup of an organization's supply and its specification phase activities are indispensible for long-term care providers who aim to do better in terms of quality and efficiency. Moreover, long-term care providers could benefit from joint provision of care and services by means of modular working teams. Based upon our findings, we are able to elaborate on how to further

  19. Modelling long term energy consumption of French residential sector - improving behavioral realism and simulating ambitious scenarios

    International Nuclear Information System (INIS)

    Allibe, Benoit

    2012-01-01

    This thesis aims to integrate components of an economic model of the behaviors of households in a technological model of French residential sector energy consumption dynamics and to analyze the consequences of this integration on the results of long-term residential energy consumption simulations (2030-2050). The results of this work highlight significant differences between the actual household space heating energy consumptions and those estimated by engineering models. These differences are largely due to the elasticity of thermal comfort demand to thermal comfort price. Our improved model makes it possible to conjointly integrate the concepts of price elasticity and rebound effect (the increase in energy service level following an improvement in energy performance of the equipment providing the service) in a daily behavior model. Regarding space heating consumption, the consequences of this behavioral adaptation - combined with some technical defects - are a significant reduction of the technical and behavioral energy saving potentials (while effective daily use of energy is generally lower than predicted by engineering models) at a national level. This implies that mid and long-term national energy policy targets (a 38% drop in primary energy consumption by 2020 and a reduction in greenhouse gas emissions by a factor of 4 by 2050 compared to the 1990 level) will be harder to reach than previously expected for the residential sector. These results also imply that a strong reduction in carbon emissions cannot be achieved solely through the diffusion of efficient technologies and energy conservation behavior but also requires to significantly lower the average carbon content of residential space heating energy through the generalized use of wood energy. The second issue addressed in this thesis is the influence of the resolution of a techno-economic model (i.e. its ability to represent the various values that a variable can have within the modeled system) on its

  20. Long-term transfer and expression of the human beta-globin gene in a mouse transplant model.

    Science.gov (United States)

    Raftopoulos, H; Ward, M; Leboulch, P; Bank, A

    1997-11-01

    Somatic gene therapy of hemoglobinopathies depends initially on the demonstration of safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models. We have used a beta-globin gene/beta-locus control region retroviral vector containing several modifications to optimize gene transfer and expression in a mouse transplant model. In this report we show that transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice leads to the continued presence of the gene up to 8 months posttransplantation. The transferred human beta-globin gene is detected in 3 of 5 mice surviving long term (>4 months) transplanted with bone marrow cells transduced with high-titer virus. Southern blotting confirms the presence of the unrearranged 5.1-kb human beta-globin gene-containing provirus in 2 of these mice. In addition, long-term expression of the transferred gene is seen in 2 mice at levels of 5% and 20% that of endogenous murine beta-globin at 6 and 8 months posttransplantation. We further document stem cell transduction by the successful transfer and high-level expression of the human beta-globin gene from mice transduced 9 months earlier into irradiated secondary recipient mice. These results demonstrate high-level, long-term somatic human beta-globin gene transfer into the hematopoietic stem cells of an animal for the first time, and suggest the potential feasibility of a retroviral gene therapy approach to sickle cell disease and the beta thalassemias.

  1. Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.

    Science.gov (United States)

    Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; Holman, Sheila; Ross, William G; Lyerly, H Kim

    2014-01-01

    The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina.

  2. Soil Water Improvements with the Long Term Use of a Winter Rye Cover Crop

    Science.gov (United States)

    Basche, A.; Kaspar, T.; Archontoulis, S.; Jaynes, D. B.; Sauer, T. J.; Parkin, T.; Miguez, F.

    2015-12-01

    The Midwestern United States, a region that produces one-third of maize and one-quarter of soybeans globally, is projected to experience increasing rainfall variability with future climate change. One approach to mitigate climate impacts is to utilize crop and soil management practices that enhance soil water storage, reducing the risks of flooding and runoff as well as drought-induced crop water stress. While some research indicates that a winter cover crop in a maize-soybean rotation increases soil water, producers continue to be concerned that water use by cover crops will reduce water for a following cash crop. We analyzed continuous in-field soil moisture measurements over from 2008-2014 at a Central Iowa research site that has included a winter rye cover crop in a maize-soybean rotation for thirteen years. This period of study included years in the top third of wettest years on record (2008, 2010, 2014) as well as years in the bottom third of driest years (2012, 2013). We found the cover crop treatment to have significantly higher soil water storage from 2012-2014 when compared to the no cover crop treatment and in most years greater soil water content later in the growing season when a cover crop was present. We further found that the winter rye cover crop significantly increased the field capacity water content and plant available water compared to the no cover crop treatment. Finally, in 2012 and 2013, we measured maize and soybean biomass every 2-3 weeks and did not see treatment differences in crop growth, leaf area or nitrogen uptake. Final crop yields were not statistically different between the cover and no cover crop treatment in any of the years of this analysis. This research indicates that the long-term use of a winter rye cover crop can improve soil water dynamics without sacrificing cash crop growth.

  3. Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality

    Science.gov (United States)

    Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; Holman, Sheila; Ross, William G; Lyerly, H Kim

    2014-01-01

    Background The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. Materials and methods We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993–2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Results Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths–with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths–with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. Conclusion Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina. PMID:25018627

  4. Improvement of Emergency Cooldown Tank in terms of long-term cooling

    International Nuclear Information System (INIS)

    Moon, Joo Hyung; Kim, Youngin; Kim, Keung Koo

    2014-01-01

    SMART received its Standard Design Approval(SDA) from Korea Government in 2012. After Fukushima accident, passively cooling system of nuclear reactor gets great attention and a consentience reached that at least 72 hours of grace time after an accident should be secured, during which a nuclear reactor remains in safe condition without any operator's intervention. To meet this requirement, SMART adapted passive cooling system such as passive residual heat removal system(PRHRS). It is composed of an emergency cooldown tank(ETC), a heat exchanger and a makeup tank. The ETC should be refilled periodically by auxiliary water supply system in order to use it beyond 72 hours. Otherwise the immersed heat exchanger would be exposed to the air, which would damage the function of PRHRS. To overcome this shortcoming, installation of an air-cooling heat exchanger at the top of the ETC is proposed as shown in Fig. 2. Here the top of the ETC is now closed. Evaporated steam is collected through the vertical duct and condensed through air-cooling heat exchanger. By natural circulation, water level of ETC can be maintained at steady state for a very long-term period. The purpose of the present study is to investigate the thermal sizing of air-cooling heat exchanger which extends the cooling period of ETC. Thermal sizing of air-cooling heat exchanger had been investigated by using several heat transfer correlations for natural convection of vertical tubes. Quantitative comparisons were made to find out how many tubes are required to remove the residual heat. This work would contribute to improve the current design of ETC and to extend the cooling period much longer than 72 hours, which will promote the passive safety function of SMART

  5. Correlating learning and memory improvements to long-term potentiation in patients with brain injury

    Institute of Scientific and Technical Information of China (English)

    Xingfu Peng; Qian Yu

    2008-01-01

    BACKGROUND:Brain injury patients often exhibit learning and memory functional deficits.Long-term potentiation(LTP)is a representative index for studying learning and memory cellular models; the LTP index correlates to neural plasticity. OBJECTIVE:This study was designed to investigate correlations of learning and memory functions to LTP in brain injury patients,and to summarize the research advancements in mechanisms underlying brain functional improvements after rehabilitation intervention. RETRIEVAL STRATEGY:Using the terms "brain injuries,rehabilitation,learning and memory,long-term potentiation",manuscripts that were published from 2000-2007 were retrieved from the PubMed database.At the same time,manuscripts published from 2000-2007 were also retrieved from the Database of Chinese Scientific and Technical Periodicals with the same terms in the Chinese language.A total of 64 manuscripts were obtained and primarily screened.Inclusion criteria:studies on learning and memory,as well as LTP in brain injury patients,and studies focused on the effects of rehabilitation intervention on the two indices; studies that were recently published or in high-impact journals.Exclusion criteria:repetitive studies.LITERATURE EVALUATION:The included manuscripts primarily focused on correlations between learning and memory and LTP,the effects of brain injury on learning and memory,as well as LTP,and the effects of rehabilitation intervention on learning and memory after brain injury.The included 39 manuscripts were clinical,basic experimental,or review studies. DATA SYNTHESIS:Learning and memory closely correlates to LTP.The neurobiological basis of learning and memory is central nervous system plasticity,which involves neural networks,neural circuits,and synaptic connections,in particular,synaptic plasticity.LTP is considered to be an ideal model for studying synaptic plasticity,and it is also a classic model for studying neural plasticity of learning and memory.Brain injury

  6. Participatory Research Into Inclusive Practice: Improving Services for People With Long Term Neurological Conditions

    Directory of Open Access Journals (Sweden)

    Tina Cook

    2017-11-01

    Full Text Available People with long-term conditions are intensive users of health services as well as being long term users of social care and community services. In the UK, the Department of Health has suggested that the development of a more inclusive approach to services could furnish benefits to people with long-term conditions and financial savings for service providers. Researchers with a varied set of expertise and experience (users of neuro-rehabilitation services, staff working in services, people working with third sector agencies and university academics adopted a participatory research approach to work together to explore what inclusion might look and feel like for people who are long term users of health services. The element of critique and mutual challenge, developed within the research process, disturbed current presentations of inclusion and inclusive practice. It revealed that the more usually expected components of inclusion (trust, respect and shared responsibility whilst necessary for inclusive practice, are not necessarily sufficient. Inclusion is revealed as a complex and challenging process that requires the active construction of a critical communicative space for dialectical and democratic learning for service development.

  7. A protocol improves GP recording of long-term sickness absence risk factors

    NARCIS (Netherlands)

    van Dijk, Paul C. M.; Hogervorst, Wouter; ter Riet, Gerben; van Dijk, Frank

    2008-01-01

    Background If general practitioners (GPs) were better informed about patients' risks of long-term sickness absence (LTSA), they could incorporate these risk assessments into their patient management plans and cooperate more with occupational physicians to prevent LTSA. Aim To evaluate the

  8. Improvement of Depression and Anxiety After Discontinuation of Long- Term Efavirenz Treatment

    NARCIS (Netherlands)

    Mothapo, K.M.; Schellekens, A.F.A.; Crevel, R. van; Keuter, M.; Grintjes-Huisman, K.; Koopmans, P.; Ven, A. van der

    2015-01-01

    Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment. This study: 1) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy; 2) explored the effect of a switch to

  9. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

    Directory of Open Access Journals (Sweden)

    Marcos Perez-Basterrechea

    Full Text Available Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  10. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

    Science.gov (United States)

    Perez-Basterrechea, Marcos; Esteban, Manuel Martinez; Alvarez-Viejo, Maria; Fontanil, Tania; Cal, Santiago; Sanchez Pitiot, Marta; Otero, Jesus; Obaya, Alvaro Jesus

    2017-01-01

    Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  11. Long-term expression of human adenosine deaminase in mice transplanted with retrovirus-infected hematopoietic stem cells

    International Nuclear Information System (INIS)

    Lim, B.; Apperley, J.F.; Orkin, S.H.; Williams, D.A.

    1989-01-01

    Long-term stable expression of foreign genetic sequences transferred into hematopoietic stem cells by using retroviral vectors constitutes a relevant model for somatic gene therapy. Such stability of expression may depend on vector design, including the presence or absence of specific sequences within the vector, in combination with the nature and efficiency of infection of the hematopoietic target cells. The authors have previously reported successful transfer of human DNA encoding adenosine deaminase (ADA) into CFU-S (colony-forming unit-spleen) stem cells using simplified recombinant retroviral vectors. Human ADA was expressed in CFU-S-derived spleen colonies at levels near to endogenous enzyme. However, because of the lack of an efficient dominant selectable marker and low recombinant viral titers, stability of long-term expression of human ADA was not examined. They report here the development of an efficient method of infection of hematopoietic stem cells (HSC) without reliance on in vitro selection. Peripheral blood samples of 100% of mice transplanted with HSC infected by this protocol exhibit expression of human ADA 30 days after transplantation. Some mice (6 of 13) continue to express human ADA in all lineages after complete hematopoietic reconstitution (4 months). The use of recombinant retroviral vectors that efficiently transfer human ADA cDNA into HSC leading to stable expression of functional ADA in reconstituted mice, provides an experimental framework for future development of approaches to somatic gene therapy

  12. Public Attitudes Toward Sexual Expression in Long-Term Care: Does Context Matter?

    Science.gov (United States)

    Yelland, Erin; Hosier, Amy

    2017-08-01

    The purpose of this study was to (a) examine how age and sex of long-term care (LTC) residents influence public attitudes toward sexuality in LTC and (b) understand how, in the absence of cognitive decline, residing in LTC influences the perception of sexuality as a basic human right. Attitudes were examined using a factorial vignette with a probability sample of 325 respondents from a southern state. Results indicate that attitudes were not statistically affected by a vignette character's age or sex; but respondent education level, parenthood status, and religious affiliation did have direct bearing on attitudes. The notion of sexuality as a basic human right for residents of LTC was ultimately challenged as 19% of respondents said that LTC residents should not be permitted to have sexual relations with their spouse in the facility.

  13. HST/WFC3: new capabilities, improved IR detector calibrations, and long-term performance stability

    Science.gov (United States)

    MacKenty, John W.; Baggett, Sylvia M.; Brammer, Gabriel; Hilbert, Bryan; Long, Knox S.; McCullough, Peter; Riess, Adam G.

    2014-08-01

    the causes of its temporal and spatial variation has led to the appreciation of the impact of He I 1.083 micron emission from the earth's atmosphere. This adds a significant and variable background to the two filters and two grisms which include this spectral feature when the HST spacecraft is outside of the earth's shadow. After nearly five years in orbit, long term trending of the scientific and engineering behavior of WFC3 demonstrates excellent stability other than the expected decline in CCD charge transfer efficiency. Addition of post-flash signal to images is shown to markedly improve the transfer efficiency for low level signals. Combined with a pixel based correction algorithm developed at STScl, CCD performance is stabilized at levels only slightly degraded from its initial values.

  14. Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

    Science.gov (United States)

    Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

    2018-06-20

    Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

  15. Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality

    Directory of Open Access Journals (Sweden)

    Kravchenko J

    2014-06-01

    Full Text Available Julia Kravchenko,1 Igor Akushevich,2 Amy P Abernethy,3 Sheila Holman,4 William G Ross Jr,5 H Kim Lyerly1,6 1Department of Surgery, 2Center for Population Health and Aging, 3Duke Clinical Research Institute, Duke University Medical Center, Duke University, Durham, 4Division of Air Quality, North Carolina Department of Environment and Natural Resources, Raleigh, 5Nicholas School of the Environment, 6Department of Pathology, Duke University Medical Center, Duke University, Durham, NC, USA Background: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. Materials and methods: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2, nitrogen dioxide (NO2, carbon monoxide (CO, and particulate matters (PM2.5 and PM10 using monthly data measurements from air-monitoring stations in North Carolina in 1993–2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Results: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths–with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths–with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only

  16. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

    2015-01-01

    Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Cases of long-term survival of ≥3 years’ duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Eighteen cases were identified that identified survival of ≥3 years’ duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3–15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison. The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself

  17. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

  18. Long-term effectiveness of a quality improvement program for patients with type 2 diabetes in general practice.

    NARCIS (Netherlands)

    Renders, C.M.; Valk, G.D.; Franse, L.V.; Schellevis, F.; Eijk, J.T.M. van; Wal, G. van der

    2001-01-01

    OBJECTIVE— To assess the long-term effectiveness of a quality improvement program on care provided and patient outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS— A nonrandomized trial was performed with 312 patients with type 2 diabetes in the intervention group and 77 patients with

  19. A Videotape-Based Training Method for Improving the Detection of Depression in Residents of Long-Term Care Facilities

    Science.gov (United States)

    Wood, Stacey; Cummings, Jeffrey L.; Schnelle, Betha; Stephens, Mary

    2002-01-01

    Purpose: This article reviews the effectiveness of a new training program for improving nursing staffs' detection of depression within long-term care facilities. The course was designed to increase recognition of the Minimal Data Set (MDS) Mood Trigger items, to be brief, and to rely on images rather than didactics. Design and Methods: This study…

  20. Improved analysis of long-term monitoring data demonstrates marked regional declines of bat populations in the eastern United States

    Science.gov (United States)

    Thomas E. Ingersoll; Brent J. Sewall; Sybill K. Amelon

    2013-01-01

    Bats are diverse and ecologically important, but are also subject to a suite of severe threats. Evidence for localized bat mortality from these threats is well-documented in some cases, but long-term changes in regional populations of bats remain poorly understood. Bat hibernation surveys provide an opportunity to improve understanding, but analysis is complicated by...

  1. Immunohistochemical expression of platelet-derived growth factor receptors in ovarian cancer patients with long-term follow-up

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Dahl Steffensen, Karina; Waldstrøm, Marianne

    2012-01-01

    relation to histopathological parameters and long-term overall survival. Methods. The immunohistochemical expression of PDGFR-α and PDGFR-β was investigated in tumor and stromal cells in 170 patients with histologically verified epithelial ovarian cancer. Results. Almost half of the tumor specimens showed......Introduction. The well-documented role of the PDGF system in tumor growth and angiogenesis has prompted the development of new biological agents targeting the PDGF system. The aim of the present study was to analyze the expression of the PDGF-receptors in ovarian cancer and to investigate its...... high expression of PDGFR-α and PDGFR-β in tumor cells (43% and 41%) and in stromal compartments (32% and 44%). There was a significant association between high expression of PDGFR-α and high expression of PDGFR-β in both tumor and stromal cells. Coexpression of PDGFR-α and PDGFR-β in stromal cells...

  2. Long-term functional impairment of hemopoietic progenitor cells engineered to express the S1 catalytic subunit of pertussis toxin.

    Science.gov (United States)

    Bonig, Halvard; Rohmer, Laurence; Papayannopoulou, Thalia

    2005-06-01

    A large body of data suggests that pertussis toxin (PTX)-sensitive G protein signals in mature and immature hemopoietic cells control their migration patterns in vitro and in vivo. These effects were derived after treatment of cells or animals with PTX. To circumvent several inherent problems of PTX holotoxin treatment, we expressed the S1 catalytic activity of PTX, thus blocking Gi protein signaling, in 32D murine myeloid progenitor cells and in primary human CD34+ cells, and studied its functional consequences. S1 was expressed using viral vectors. Effects of Gi protein blockade on proliferation, migration, adhesion, and gene expression were tested in vitro. S1 expression was nontoxic for the cells; expression and function were stable long-term and not overridden by compensatory mechanisms. S1-transduced 32D cells and primary CD34+ cells migrated poorly and did not contract their cytoskeleton upon treatment with the chemoattractant stromal cell-derived factor -1 (SDF-1), similar to the phenotype induced by PTX treatment. Gene expression studies comparing S1-transduced and control 32D cells uncovered four genes, expression of which was regulated by Gi protein blockade. Of interest, although SDF-1 signaling was inhibited, comparison between SDF-1-treated and untreated cells suggests that SDF-1 stimulation does not depend on de novo gene expression in these cells. Furthermore, when injected into nonobese diabetic/severe combined immunodeficient mice, seeding of S1-expressing 32D cells to bone marrow was largely blocked. Expression of S1 is an effective approach for studying long-term functional consequences of Gi protein blockade in hemopoietic cells in vitro and in vivo.

  3. Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

    Science.gov (United States)

    Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina

    2016-11-29

    SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

  4. Enhanced green fluorescent protein is a nearly ideal long-term expression tracer for hematopoietic stem cells, whereas DsRed-express fluorescent protein is not.

    Science.gov (United States)

    Tao, Wen; Evans, Barbara-Graham; Yao, Jing; Cooper, Scott; Cornetta, Kenneth; Ballas, Christopher B; Hangoc, Giao; Broxmeyer, Hal E

    2007-03-01

    Validated gene transfer and expression tracers are essential for elucidating functions of mammalian genes. Here, we have determined the suitability and unintended side effects of enhanced green fluorescent protein (EGFP) and DsRed-Express fluorescent protein as expression tracers in long-term hematopoietic stem cells (HSCs). Retrovirally transduced mouse bone marrow cells expressing either EGFP or DsRed-Express in single or mixed dual-color cell populations were clearly discerned by flow cytometry and fluorescence microscopy. The results from in vivo competitive repopulation assays demonstrated that EGFP-expressing HSCs were maintained nearly throughout the lifespan of the transplanted mice and retained long-term multilineage repopulating potential. All mice assessed at 15 months post-transplantation were EGFP positive, and, on average, 24% total peripheral white blood cells expressed EGFP. Most EGFP-expressing recipient mice lived at least 22 months. In contrast, Discosoma sp. red fluorescent protein (DsRed)-expressing donor cells dramatically declined in transplant-recipient mice over time, particularly in the competitive setting, in which mixed EGFP- and DsRed-expressing cells were cotransplanted. Moreover, under in vitro culture condition favoring preservation of HSCs, purified EGFP-expressing cells grew robustly, whereas DsRed-expressing cells did not. Therefore, EGFP has no detectable deteriorative effects on HSCs, and is nearly an ideal long-term expression tracer for hematopoietic cells; however, DsRed-Express fluorescent protein is not suitable for these cells.

  5. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

    Directory of Open Access Journals (Sweden)

    Paula Mera

    Full Text Available Lipid metabolism in the ventromedial hypothalamus (VMH has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH, long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT and reduced vesicular glutamate transporter 2 (VGLUT2 expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

  6. Long-term oxygen therapy for COPD. Improving longevity and quality of life in hypoxemic patients.

    Science.gov (United States)

    Weg, J G; Haas, C F

    1998-04-01

    Long-term oxygen therapy can increase life expectancy in hypoxemic patients with COPD. Accurate identification of hypoxemia requires arterial blood gas measurements. Pulse oximetry can be used to measure trends in oxygenation, oxygen needs, and oxygen requirements during exercise and sleep. A detailed oxygen prescription indicates: (1) the oxygen dose (L/min), (2) the number of hours per day that oxygen therapy is required, (3) the dose required during exercise, (4) the oxygen supply system: concentrator, compressed gas cylinder, or liquid oxygen reservoir, and (5) the delivery device: nasal cannula, demand-flow device, reservoir cannula, or transtracheal oxygen catheter.

  7. Early pathologic findings and long-term improvement in anti-Ma2-associated encephalitis.

    Science.gov (United States)

    Blumenthal, D T; Salzman, K L; Digre, K B; Jensen, R L; Dunson, W A; Dalmau, J

    2006-07-11

    A 67-year-old man sequentially developed anti-Ma2-associated paraneoplastic encephalitis (PNE) and contralateral herpes simplex encephalitis (HSE). Brain biopsy 1 month before HSE revealed extensive infiltrates of T cells, B cells, and plasma cells. Most T cells expressed the cytotoxic granule-associated protein TIA-1 and the membranolytic protein granzyme-B. Although recovery was thought to be unlikely, treatment of the PNE with corticosteroids and resection of the associated lung cancer resulted in dramatic improvement for 21 months.

  8. Long term neurocognitive improvement after "late" right hemispherectomy: case report and review of the literature.

    Science.gov (United States)

    Moletto, Alessandra; Bagnasco, Irene; Dassi, Patrizia; Vigliano, Piernanda

    2018-03-21

    To study the long-term neurocognitive changes of a right-handed girl with intractable epilepsy after late right hemispherectomy and compare them with data in the literature. The girl was affected by an epileptic encephalopathy associated with right fronto-temporo-parietal polymicrogyria; she was submitted to right hemispherectomy at the age of 5 and examined with cognitive and neuropsychological tests at the age of 17 years. The girl took advantage of neurocognitive rehabilitation for several years; she is currently seizure-free and off therapy. At the end of the follow-up, the full-scale IQ is stable and within the normal range (p = 88). As the discrepancy between verbal IQ (pp = 120) and performance IQ (pp = 71) is significantly high, the girl was subjected to neurocognitive evaluation with the following results: verbal problem solving, verbal short- and long-term memory, and executive functions are within normal range. The most fragile functional areas are visual and spatial reasoning, verbal working memory, short-term visuospatial memory, visual attention, and processing speed, all > 2 SD. The spatial tests, such as coding, matrix reasoning, picture concepts, and arithmetic reasoning (which are favored by other functions such as associative memory and learning ability), are less severely impaired. These findings show that good conceptual skills and verbal reasoning can compensate for some deficits in visual-perceptual and visuospatial functions.

  9. Long-term Dietary Macronutrients and Hepatic Gene Expression in Aging Mice.

    Science.gov (United States)

    Gokarn, Rahul; Solon-Biet, Samantha M; Cogger, Victoria C; Cooney, Gregory J; Wahl, Devin; McMahon, Aisling C; Mitchell, James R; Mitchell, Sarah J; Hine, Christopher; de Cabo, Rafael; Raubenheimer, David; Simpson, Stephen J; Le Couteur, David G

    2018-04-23

    Nutrition influences both hepatic function and aging, but mechanisms are poorly understood. Here, the effects of lifelong, ad libitum-fed diets varying in macronutrients and energy on hepatic gene expression were studied. Gene expression was measured using Affymetrix mouse arrays in livers of 46 mice aged 15 months fed one of 25 diets varying in protein, carbohydrates, fat, and energy density from 3 weeks of age. Gene expression was almost entirely influenced by protein intake. Carbohydrate and fat intake had few effects on gene expression compared with protein. Pathways and processes associated with protein intake included those involved with mitochondrial function, metabolic signaling (PI3K-Akt, AMPK, mTOR) and metabolism of protein and amino acids. Protein intake had variable effects on genes associated with regulation of longevity and influenced by caloric restriction. Among the genes of interest with expression that were significantly associated with protein intake are Cth, Gls2, Igf1, and Nnmt, which were increased with higher protein intake, and Igf2bp2, Fgf21, Prkab2, and Mtor, which were increased with lower protein intake. Dietary protein has a powerful impact on hepatic gene expression in older mice, with some overlap with genes previously reported to be involved with regulation of longevity or caloric restriction.

  10. Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

    Science.gov (United States)

    Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

    2017-07-12

    The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

  11. Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences

    Science.gov (United States)

    Dumeige, Laurence; Storey, Caroline; Decourtye, Lyvianne; Nehlich, Melanie; Lhadj, Christophe; Viengchareun, Say; Kappeler, Laurent; Lombès, Marc; Martinerie, Laetitia

    2017-01-01

    Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance. The role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11 β-hydroxysteroid dehydrogenase type 2 (11βHSD2) protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using liquid-chromatography coupled to mass spectrometry in tandem (LC-MSMS) method. SBP and HR were found to be significantly lower in females compared to males. This was accompanied by a sex- and tissue-specific expression profile throughout renal development of the mineralocorticoid target genes serum and glucocorticoid-regulated kinase 1 (Sgk1) and glucocorticoid-induced leucine zipper protein (Gilz), together with Hsd11b2, Finally, the implication of sex hormones in this sex-specific expression profile was demonstrated in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of the mineralocorticoid pathway that could have important implications in physiology and pathology. PMID:28230786

  12. Expression of HSPs: an adaptive mechanism during long-term heat stress in goats ( Capra hircus)

    Science.gov (United States)

    Dangi, Satyaveer Singh; Gupta, Mahesh; Dangi, Saroj K.; Chouhan, Vikrant Singh; Maurya, V. P.; Kumar, Puneet; Singh, Gyanendra; Sarkar, Mihir

    2015-08-01

    Menacing global rise in surface temperature compelled more focus of research over understanding heat stress response mechanism of animals and mitigation of heat stress. Twenty-four goats divided into four groups ( n = 6) such as NHS (non-heat-stressed), HS (heat-stressed), HS + VC (heat-stressed administered with vitamin C), and HS + VE + Se (heat-stressed administered with vitamin E and selenium). Except NHS group, other groups were exposed to repeated heat stress (42 °C) for 6 h on 16 consecutive days. Blood samples were collected at the end of heat exposure on days 1, 6, 11, and 16. When groups compared between days, expression of all heat shock proteins (HSPs) showed a similar pattern as first peak on day 1, reached to basal level on the sixth day, and followed by second peak on day 16. The relative messenger RNA (mRNA) and protein expression of HSP 60, HSP70, and HSP90 was observed highest ( P < 0.05) in HS group, followed by antioxidant-administered group on days 1 and 16, which signifies that antioxidants have dampening effect on HSP expression. HSP105/110 expression was highest ( P < 0.05) on day 16. We conclude that HSP expression pattern is at least two-peak phenomenon, i.e., primary window of HSP protection on the first day followed by second window of protection on day 16. HSP60, HSP70, and HSP90 play an important role during the initial phase of heat stress acclimation whereas HSP105/110 joins this cascade at later phase. Antioxidants may possibly attenuate the HSP expression by reducing the oxidative stress.

  13. Estimation of Ship Long-term Wave-induced Bending Moment using Closed-Form Expressions

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher; Mansour, A. E.

    2002-01-01

    A semi-analytical approach is used to derive frequency response functions and standard deviations for the wave-induced bending moment amidships for mono-hull ships. The results are given as closed-form expressions and the required input information for the procedure is restricted to the main......-empirical closed-form expression for the skewness. The effect of whipping is included by assuming that whipping and wave-induced responses are conditionally independent given Hs. The procedure is simple and can be used to make quick estimates of the design wave bending moment at the conceptual design phase...

  14. Long-term neuroglobin expression of human astrocytes following brain trauma.

    Science.gov (United States)

    Chen, Xiameng; Liu, Yuan; Zhang, Lin; Zhu, Peng; Zhu, Haibiao; Yang, Yu; Guan, Peng

    2015-10-08

    Neuroglobin (Ngb), a 17 kDa monomeric protein, was initially described as a vertebrate oxygen-binding heme protein in 2000 and detected in metabolically active organs or cells, like the brain, peripheral nervous system as well as certain endocrine cells. A large array of initial experimental work reported that Ngb displayed a neuron restricted expression pattern in mammalian brains. However, growing evidence indicated astrocytes may also express Ngb under pathological conditions. To address the question whether human astrocytes express Ngb under traumatic insults, we investigated Ngb immuno-reactivity in post-mortem human brain tissues that died of acute, sub-acute and chronic brain trauma, respectively. We observed astrocytic Ngb expression in sub-acute and chronic traumatic brains rather than acute traumatic brains. Strikingly, the Ngb immuno-reactive astrocytes were still strongly detectable in groups that died 12 months after brain trauma. Our findings may imply an unexplored role of Ngb in astrocytes and the involved mechanisms were suggested to be further characterized. Also, therapeutic application of Ngb or Ngb-inducible chemical compounds in neuro-genesis or astrocytic scar forming can be expected. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. [Preoperational study for the improvement of hygiene conditions in long-term care facilities].

    Science.gov (United States)

    Adler, A C; Spegel, H; Kolb, S; Hierl, W; Müller, C; Höller, C; Liebl, B; Rudolph, P; Herr, C

    2014-12-01

    Hygiene is becoming more and more important in long-term care facilities. Long-term care facilities are subject to monitoring by the Public Health Service (PHS) and other authorities. For the PHS in Bavaria the Bavarian Health and Food Safety Authority (Landesamt für Gesundheit und Lebensmittelsicherheit, LGL) published a hygiene monitoring concept and there exists an inspection guide developed by a specialist department for nursing homes and institutions for the handicapped (Fachstelle für Pflege und Behinderteneinrichtungen, FQA). Because inspections are performed in multiprofessional teams, it makes sense to use a coordinated inspection catalog. The aim was to integrate hygienic requirements specified in the Bavarian guidelines for hygiene by the LGL into the inspection guide published by the FQA to obtain a quality assured surveillance. The involved parties were questioned about the inspection guide and their hygiene management and then the hygiene criteria of the LGL were implemented into the inspection guide. Questions dealing with hygiene requirements concerning intensive care, management of multidrug resistant bacteria and interviews with the person responsible for infection control in the facility itself were developed for the first time and were integrated into the inspection guide. The revised inspection guide was tested for its applicability. With the revised inspection guide there now exists a tool which allows not only comprehensive inspections of the facilities including hygiene issues but also a good cooperation of the various parties involved. There are many actions which have to be conveyed into the future, especially programs to train staff to apply the inspection guide and to enhance the ability of all participants to act in cooperation. The guide will also allow the facilities to cooperate more easily and more closely, as the guide takes the respective problems and challenges of the different facilities into consideration. Additionally the

  16. Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning.

    Science.gov (United States)

    Cevik, Ozge Selin; Sahin, Leyla; Tamer, Lulufer

    2018-05-01

    The type and duration of exposure to stress is an important influence on emotional and cognitive functions. Learning is the adaptive response of the central nervous system that occurs in hippocampus which affects from environmental factors like exercise. In this study, we investigated effects of long term treadmill exercise on learning and behavior on chronic social isolated rat. Male Wistar rats (n = 32) randomly assigned into four groups: control, exercised, social isolation, social isolation + exercise during postnatal days (PNDs) 21-34. Social isolation protocol was applied during 14 days by placing rat in a cage one by one. Rats were exercised during 5 days, days were chosen randomly for overall 4 weeks (20, 30, 50, 60 min respectively). Finally, learning performance was evaluated by Morris water maze (MWM). Anxiety behavior was evaluated by Open field and elevated plus maze test. At the end of learning and behavior tests, the rats were decapitated to collect blood samples via intracardiac puncture and corticosterone analysis was performed with ELISA method. Animal weights and water consumption did not change significantly but food intake differed among groups. Corticosterone level did not change between groups. The frequency of entering to the target quadrant increased in exercised rat significantly. However, there was no difference in learning and memory in rats. Treadmill exercise reduced anxiety behavior significantly. Taken together these findings may point out that, long term treadmill exercise did not change learning and memory but reduced anxiety level of rat without changing corticosterone level. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Improved maternal nutrition decreases children’s long-term risk of non-communicable diseases (NCDs) and obesity

    DEFF Research Database (Denmark)

    Robertson, Aileen

    Improved maternal nutrition to decrease children’s long-term risk of non-communicable diseases (NCDs) and obesity The nutritional well-being of pregnant women affects not only their health and their fetuses' development but also children's long-term risk of developing NCDs or obesity, according...... to a new report from WHO/Europe. "Good maternal nutrition. The best start in life" was launched under the auspices of the Minister of Health of Latvia during a consultation on maternal nutrition, in Riga on 27–28 June 2016. While the importance of good nutrition in the early development of children has...... – affects not only her child's health as an infant but also the child's risk of obesity and related chronic diseases as an adult. In short, maternal nutrition can truly have an intergenerational impact. Fighting NCDs and obesity through measures to improve maternal nutrition: NCDs are the leading cause...

  18. Effect of long-term actual spaceflight on the expression of key genes encoding serotonin and dopamine system

    Science.gov (United States)

    Popova, Nina; Shenkman, Boris; Naumenko, Vladimir; Kulikov, Alexander; Kondaurova, Elena; Tsybko, Anton; Kulikova, Elisabeth; Krasnov, I. B.; Bazhenova, Ekaterina; Sinyakova, Nadezhda

    The effect of long-term spaceflight on the central nervous system represents important but yet undeveloped problem. The aim of our work was to study the effect of 30-days spaceflight of mice on Russian biosatellite BION-M1 on the expression in the brain regions of key genes of a) serotonin (5-HT) system (main enzymes in 5-HT metabolism - tryptophan hydroxylase-2 (TPH-2), monoamine oxydase A (MAO A), 5-HT1A, 5-HT2A and 5-HT3 receptors); b) pivotal enzymes in DA metabolism (tyrosine hydroxylase, COMT, MAO A, MAO B) and D1, D2 receptors. Decreased expression of genes encoding the 5-HT catabolism (MAO A) and 5-HT2A receptor in some brain regions was shown. There were no differences between “spaceflight” and control mice in the expression of TPH-2 and 5-HT1A, 5-HT3 receptor genes. Significant changes were found in genetic control of DA system. Long-term spaceflight decreased the expression of genes encoding the enzyme in DA synthesis (tyrosine hydroxylase in s.nigra), DA metabolism (MAO B in the midbrain and COMT in the striatum), and D1 receptor in hypothalamus. These data suggested that 1) microgravity affected genetic control of 5-HT and especially the nigrostriatal DA system implicated in the central regulation of muscular tonus and movement, 2) the decrease in the expression of genes encoding key enzyme in DA synthesis, DA degradation and D1 receptor contributes to the movement impairment and dyskinesia produced by the spaceflight. The study was supported by Russian Foundation for Basic Research grant No. 14-04-00173.

  19. Heparanase Expression in Malignant Salivary Gl, Tumors Inversely Correlates with Long-Term Survival

    Directory of Open Access Journals (Sweden)

    Ofer Ben-Izhak

    2006-10-01

    Full Text Available BACKGROUND: Upregulation of the endo-b-Dglucuronidase, heparanase, was noted in an increasing number of human malignancies. Heparanase expression correlated with enhanced local, distant metastatic spread, increased vascular density, reduced postoperative survival. PATIENTS, METHODS: We analyzed heparanase expression in 60 patients (aged 59 ± 17 years with malignant salivary tumors (39 males, 21 females using immunohistochemistry. We applied antiheparanase antibody 733, which has previously been shown to preferentially recognize a 50-kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining can directly be correlated with enzymatic activity. RESULTS: Heparanase staining was positive (> 0 in 70% of tumors (42 of 60 patients, was negative (0 in the remaining 30% (18 patients. The cumulative survival of patients diagnosed as heparanase-negative (n = 18 at 300 months was 70% (95% confidence interval = 35-88. In contrast, the cumulative survival of patients diagnosed as heparanase-positive (n = 42 at 300 months was 0% (statistically significant difference, P = .035. CONCLUSIONS: Heparanase expression levels inversely correlate with the survival rates of salivary gl, cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy, an attractive target for anticancer drug development.

  20. Repeated batch fermentation of immobilized E. coli expressing Vitreoscilla hemoglobin for long-term use.

    Science.gov (United States)

    Sar, Taner; Seker, Gamze; Erman, Ayse Gokce; Stark, Benjamin C; Yesilcimen Akbas, Meltem

    2017-09-03

    This study describes an efficient and reusable process for ethanol production from medium containing whey powder, using alginate immobilized ethanologenic E. coli strains either expressing (TS3) or not expressing (FBR5) Vitreoscilla hemoglobin. Reuseabilities of the FBR5 and TS3 strains were investigated regarding their ethanol production capacities over the course of 15 successive 96-h batch fermentations. The ethanol production was fairly stable over the entire duration of the experiment, with strain TS3 maintaining a substantial advantage over strain FBR5. Storage of both strains in 2 different solutions for up to 60 d resulted in only a modest loss of ethanol production, with strain TS3 consistently outperforming strain FBR5 by a substantial amount. Strains stored for 15 or 30 d maintained their abilities to produce ethanol without dimunition over the course of 8 successive batch fermentations; again strain TS3 maintained a substantial advantage over strain FBR5 throughout the entire experiment. Thus, immobilization is a useful strategy to maintain the advantage in ethanol productivity afforded by expression of Vitreoscilla hemoglobin over long periods of time and large numbers of repeated batch fermentations, including, as in this case, using media with food processing wastes as the carbon source.

  1. Barriers and Facilitators to Implementing a Change Initiative in Long-Term Care Using the INTERACT® Quality Improvement Program.

    Science.gov (United States)

    Tappen, Ruth M; Wolf, David G; Rahemi, Zahra; Engstrom, Gabriella; Rojido, Carolina; Shutes, Jill M; Ouslander, Joseph G

    Implementation of major organizational change initiatives presents a challenge for long-term care leadership. Implementation of the INTERACT® (Interventions to Reduce Acute Care Transfers) quality improvement program, designed to improve the management of acute changes in condition and reduce unnecessary emergency department visits and hospitalizations of nursing home residents, serves as an example to illustrate the facilitators and barriers to major change in long-term care. As part of a larger study of the impact of INTERACT® on rates of emergency department visits and hospitalizations, staff of 71 nursing homes were called monthly to follow-up on their progress and discuss successful facilitating strategies and any challenges and barriers they encountered during the yearlong implementation period. Themes related to barriers and facilitators were identified. Six major barriers to implementation were identified: the magnitude and complexity of the change (35%), instability of facility leadership (27%), competing demands (40%), stakeholder resistance (49%), scarce resources (86%), and technical problems (31%). Six facilitating strategies were also reported: organization-wide involvement (68%), leadership support (41%), use of administrative authority (14%), adequate training (66%), persistence and oversight on the part of the champion (73%), and unfolding positive results (14%). Successful introduction of a complex change such as the INTERACT® quality improvement program in a long-term care facility requires attention to the facilitators and barriers identified in this report from those at the frontline.

  2. Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

    DEFF Research Database (Denmark)

    Jin, Xin; Nowell, Craig S; Ulyanchenko, Svetlana

    2014-01-01

    does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6...... months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove...... a valuable method for long term maintenance of TEPC in vitro....

  3. The dynamics of long-term transgene expression in engrafted neural stem cells.

    Science.gov (United States)

    Lee, Jean-Pyo; Tsai, David J; In Park, Kook; Harvey, Alan R; Snyder, Evan Y

    2009-07-01

    To assess the dynamics and confounding variables that influence transgene expression in neural stem cells (NSCs), we generated distinct NSC clones from the same pool of cells, carrying the same reporter gene transcribed from the same promoter, transduced by the same retroviral vector, and transplanted similarly at the same differentiation state, at the same time and location, into the brains of newborn mouse littermates, and monitored in parallel for over a year in vivo (without immunosuppression). Therefore, the sole variables were transgene chromosomal insertion site and copy number. We then adapted and optimized a technique that tests, at the single cell level, persistence of stem cell-mediated transgene expression in vivo based on correlating the presence of the transgene in a given NSC's nucleus (by fluorescence in situ hybridization [FISH]) with the frequency of that transgene's product within the same cell (by combined immunohistochemistry [IHC]). Under the above-stated conditions, insertion site is likely the most contributory variable dictating transgene downregulation in an NSC after 3 months in vivo. We also observed that this obstacle could be effectively and safely counteracted by simple serial infections (as few as three) inserting redundant copies of the transgene into the prospective donor NSC. (The preservation of normal growth control mechanisms and an absence of tumorigenic potential can be readily screened and ensured ex vivo prior to transplantation.) The combined FISH/IHC strategy employed here for monitoring the dynamics of transgene expression at the single cell level in vivo may be used for other types of therapeutic and housekeeping genes in endogenous and exogenous stem cells of many organs and lineages. Copyright 2009 Wiley-Liss, Inc.

  4. Chorionic villi derived mesenchymal like stem cells and expression of embryonic stem cells markers during long-term culturing.

    Science.gov (United States)

    Katsiani, E; Garas, A; Skentou, C; Tsezou, A; Messini, C I; Dafopoulos, K; Daponte, A; Messinis, I E

    2016-09-01

    Mesenchymal stem cells (MSCs) can be obtained from a variety of human tissues. MSCs derived from placental chorionic villi of the first trimester are likely to resemble, biologically, embryonic stem cells (ESC), due to the earlier development stage of placenta. In the present study long-term cultures of MSC-like cells were assessed in order to evaluate MSCs multipotent characteristics and molecular features during the period of culture. CV-cells obtained from 10 samples of chorionic villus displayed typical fibroblastoid morphology, undergone 20 passages during a period of 120 days, maintaining a stable karyotype throughout long term expansion. The cells were positive, for CD90, CD73, CD105, CD29, CD44, HLA ABC antigens and negative for CD14, CD34, AC133, and HLA DR antigens as resulted from the flow cytometry analysis. CV-cells were differentiated in adipocytes, osteoblasts, chondrocytes and neuronal cells under specific culture conditions. The expression of the ESC-gene markers POU5F1 (Oct-4) and NANOG was observed at earliest stages (4-12 passages) and not at the late stages (14-20 passages) by RT-PCR analysis. ZFP42 and SOX2 expression were not detected. Moreover, CV-cells were found to express GATA4 but not NES (Nestin). Chorionic villi-derived cells possess multipotent properties, display high proliferation rate and self-renew capacity, share common surface antigens with adult MSCs and express certain embryonics stem cells gene markers. These characteristics highlight chorionic villi as an attractive source of MSCs for the needs of regenerative medicine.

  5. Plastic surgery improves long-term weight control after bariatric surgery.

    Science.gov (United States)

    Balagué, Nicolas; Combescure, Christophe; Huber, Olivier; Pittet-Cuénod, Brigitte; Modarressi, Ali

    2013-10-01

    The positive impact of Roux-en-Y gastric bypass on weight, comorbidities, and health-related quality of life is well documented. However, 50 percent of patients regain some of the lost weight after 2 years with Roux-en-Y gastric bypass and present a mean weight regain of 10 to 15 percent after several years, partially losing the previously obtained benefits. The authors hypothesize that body contouring could decrease weight regain, leading to better long-term weight control after Roux-en-Y gastric bypass. In a matched control study, variations in weight for 98 patients with body contouring after Roux-en-Y gastric bypass were compared with those of 102 matched control patients with Roux-en-Y gastric bypass alone. Data were collected prospectively at 1, 3, 6, 9, 12, and 18 months after Roux-en-Y gastric bypass and then yearly until 7 years. After a massive mean weight loss of 45.2 kg during the first 2 years after Roux-en-Y gastric bypass, patients with Roux-en-Y gastric bypass alone presented a higher continuous mean weight regain than those with Roux-en-Y gastric bypass and body contouring (1.78 kg/year versus 0.51 kg/year of weight regain, respectively; p = 0.001). After 7 years, patients with Roux-en-Y gastric bypass presented significantly higher mean weight regain than patients with Roux-en-Y gastric bypass and body contouring (i.e., 10.8 percent versus 3.6 percent mean weight gain, respectively; p weight of 2.04 kg by body contouring, the weight regain was 22.9 kg for patients with Roux-en-Y gastric bypass alone and only 6.2 kg for those with Roux-en-Y gastric bypass and body contouring. The authors demonstrated that patients with body contouring present better long-term weight control after Roux-en-Y gastric bypass. Therefore, body contouring must be considered as a reconstructive operation in the treatment of morbid obesity. Therapeutic, III.

  6. Long-term survival of transplanted allogeneic cells engineered to express a T cell chemorepellent.

    Science.gov (United States)

    Papeta, Natalia; Chen, Tao; Vianello, Fabrizio; Gererty, Lyle; Malik, Ashish; Mok, Ying-Ting; Tharp, William G; Bagley, Jessamyn; Zhao, Guiling; Stevceva, Liljana; Yoon, Victor; Sykes, Megan; Sachs, David; Iacomini, John; Poznansky, Mark C

    2007-01-27

    Alloantigen specific T cells have been shown to be required for allograft rejection. The chemokine, stromal cell derived factor-1 (SDF-1) at high concentration, has been shown to act as a T-cell chemorepellent and abrogate T-cell infiltration into a site of antigen challenge in vivo via a mechanism termed fugetaxis or chemorepulsion. We postulated that this mechanism could be exploited therapeutically and that allogeneic cells engineered to express a chemorepellent protein would not be rejected. Allogeneic murine insulinoma beta-TC3 cells and primary islets from BALB/C mice were engineered to constitutively secrete differential levels of SDF-1 and transplanted into allogeneic diabetic C57BL/6 mice. Rejection was defined as the permanent return of hyperglycemia and was correlated with the level of T-cell infiltration. The migratory response of T-cells to SDF-1 was also analyzed by transwell migration assay and time-lapse videomicroscopy. The cytotoxicity of cytotoxic T cell (CTLs) against beta-TC3 cells expressing high levels of SDF-1 was measured in standard and modified chromium-release assays in order to determine the effect of CTL migration on killing efficacy. Control animals rejected allogeneic cells and remained diabetic. In contrast, high level SDF-1 production by transplanted cells resulted in increased survival of the allograft and a significant reduction in blood glucose levels and T-cell infiltration into the transplanted tissue. This is the first demonstration of a novel approach that exploits T-cell chemorepulsion to induce site specific immune isolation and thereby overcomes allograft rejection without the use of systemic immunosuppression.

  7. Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.

    Science.gov (United States)

    Brenner, Hermann; Jansen, Lina

    2016-02-01

    Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Neural Rhythms of Change: Long-Term Improvement after Successful Treatment in Children with Disruptive Behavior Problems

    Directory of Open Access Journals (Sweden)

    Steven Woltering

    2015-01-01

    Full Text Available Neural changes were investigated for children with disruptive behavior problems one year after a treatment program ended. Thirty-nine children and their parents visited the research lab before, after, and a year after treatment ended. During those lab visits, electroencephalography (EEG was recorded during a challenging Go/No-go task. Treatment consisted of intensive 14-week combined cognitive behavioral therapy and parent management training sessions. For the analysis, participants were divided into long-term improvers (IMPs and long-term nonimprovers (NIMPs based on changes in their externalizing problem scores. The results showed early no-go theta power (4–8 Hz, 100–250 ms decreased for long-term IMPs compared to NIMPs. When participants were divided based on changes in their comorbid internalizing symptoms, effects were stronger and reductions in theta power were found for early as well as later phases (250–650 ms. We provided preliminary evidence that theta power is a useful neural measure to trace behavioral change linked to improved self-regulation even up to a year after treatment ended. Results may have implications for the characterization of children with disruptive behavior problems and may lead to the development of novel markers of treatment success.

  9. Staff's reactions towards partnered sexual expressions involving people with dementia living in long-term care facilities.

    Science.gov (United States)

    Villar, Feliciano; Celdrán, Montserrat; Serrat, Rodrigo; Fabà, Josep; Martínez, Teresa

    2018-05-01

    To explore staff responses, in terms of common practices, towards partnered sexual relationships in long-term care facilities where one or both people involved have dementia. It also tries to determine personal and institutional factors influencing these responses. Although some studies, mostly qualitative, have focused on reactions to residents' sexual expressions so far the issue has not been assessed in a study using large and diverse samples. Cross-sectional quantitative study using vignette technique. Participants were 2,295 staff members at 152 Spanish long-term care facilities. Data were collected during 2016. A vignette describing sexual situations involving people with dementia was presented to participants. After the vignette, participants had to answer the question: "What do you think most of your colleagues would do in this situation?" with nine possible responses. Results showed that relationships involving persons with dementia were perceived as potentially problematic by staff. In both conditions, discussing the case with a colleague or supervisor was the most frequently chosen reaction. More restrictive reactions were mentioned when only one person with dementia was involved in the relationship. Factors such as participants" age and years of experience, professional post and commitment to person-centred care practices were related with the frequency of common restriction practices. Results highlight the importance of providing staff with clear guidelines regarding the management of specific sexual situations to avoid stereotyped restrictive reactions. © 2017 John Wiley & Sons Ltd.

  10. Characterization, Improvement and Long Term Evaluation Of Cementitious Waste Products. An Indian Scenario

    International Nuclear Information System (INIS)

    Yaeotikar, R.G.; Rakesh, R.R.; Shirole, A.; Paul, B.; Valsala, T.P.; Choudhury, D.K.

    2013-01-01

    Cement is a very good matrix for immobilization for different types of wastes. In India, the cementation process has been adopted and used for the last four decades. Depending on the waste composition, there is need to formulate the cement waste matrix appropriately to ensure adequate compressive strength and chemical durability. This has been achieved by using different additives/backfill materials during the cementation process with cements for example Ordinary Portland Cement (OPC) and Slag Based Cements (SBC). Backfill materials studied include vermiculite and bentonite. They were evaluated for sorption characteristics, particle size distribution, water equilibration, etc. They were incorporated in the OPC-CWP (Cement Waste Product) with various waste compositions. The composition developed for ILW generated during reprocessing and during spent solvent hydrolysis were successfully adopted on a plant scale. Some of the compositions which are being developed are also in the process of being adopted in-plant. The long-term evaluation study of the CWP was carried out at actual site conditions where CWP in carbon steel drum, plastic drums and bare CWP were disposed in 2001 and removed in 2010: parameters including compressive strength and release of activity to the soil were measured. (author)

  11. Long-term CPAP treatment improves asthma control in patients with asthma and obstructive sleep apnoea.

    Science.gov (United States)

    Kauppi, Paula; Bachour, Patrick; Maasilta, Paula; Bachour, Adel

    2016-12-01

    Both asthma and obstructive sleep apnoea cause sleep disturbance, daytime sleepiness and diminished quality of life. Continuous positive airway pressure (CPAP) is efficient in reducing symptoms related to sleep apnoea. Here we report the impact of long-term use of CPAP on asthma symptoms. A survey questionnaire was distributed to all of our obstructive sleep apnoea patients with CPAP therapy in 2013. We used the Finnish version of the Asthma Control Test™ (ACT) and a visual analogue scale (0 = no symptoms, 100 = severe asthma symptoms). Asthma was defined as self-reported physician-diagnosed disease and a special reimbursement for asthma medication by the Social Insurance Institution. We sent 2577 questionnaires and received 1586 answers (61 %). One hundred ninety-seven patients were asthmatics with a prevalence of asthma among CPAP users of 13 %. We studied 152 patients (58 females) whose CPAP therapy was initiated after starting asthma medication. Their mean (SD) age was 62 (10) years, duration of CPAP 5.7 (4.7) years and their CPAP daily use was 6.3 (2.4) h. Self-reported asthma severity decreased significantly from 48.3 (29.6) to 33.1 (27.4) (p CPAP (P CPAP in patients with both asthma and obstructive sleep apnoea.

  12. Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation.

    Science.gov (United States)

    McCoy, Portia; Norton, Thomas T; McMahon, Lori L

    2008-07-01

    Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

  13. NMDA receptor expression and C terminus structure in the rotifer Brachionus plicatilis and long-term potentiation across the Metazoa.

    Science.gov (United States)

    Kenny, Nathan J; Dearden, Peter K

    2013-12-01

    The C termini of N-methyl-D-aspartate (NMDA) receptor NR2 subunits are thought to play a major role in the molecular establishment of memory across the Bilateria, via the phenomenon known as long-term potentiation (LTP). Despite their long history of use as models in the study of memory, the expression and structure of the NR2 subunit in the Lophotrochozoa has remained uncategorized. Here, we report the phylogenic relationships of NR subunits across the Bilateria, and the cloning and in situ analysis of expression of NMDA NR1 and NR2 subunits in the monogont rotifer Brachionus plicatilis. RNA in situ hybridization suggests expression of NMDA receptor subunits in B. plicatilis is neural, consistent with expression observed in other species, and ours is the first report confirming NR2 expression in the lophotrochozoan clade. However, the single NR2 subunit identified in B. plicatilis was found to lack the long C terminal domain found in vertebrates, which is believed to modulate LTP. Further investigation revealed that mollusc and annelid NR2 subunits possess long intracellular C terminal domains. As data from molluscs (and particularly Aplysia californica) are the basis for much of our understanding of LTP, understanding how these diverse lophotrochozoan C termini function in vivo will have many implications for how we consider the evolution of the molecular control of learning and memory across the Metazoa as a whole and interpret the results of experiments into this vital component of cognition.

  14. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Geun Young Lee

    2017-09-01

    Full Text Available AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG. METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS: The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038. A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810. The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05. CONCLUSION: ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

  15. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma.

    Science.gov (United States)

    Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

    2017-01-01

    To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group ( P =0.038). A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups ( P =0.810). The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group ( P =0.05). ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

  16. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    Science.gov (United States)

    Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

    2017-01-01

    AIM To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038). A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810). The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05). CONCLUSION ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density. PMID:28944196

  17. A protocol improves GP recording of long-term sickness absence risk factors.

    Science.gov (United States)

    van Dijk, Paul; Hogervorst, Wouter; ter Riet, Gerben; van Dijk, Frank

    2008-06-01

    If general practitioners (GPs) were better informed about patients' risks of long-term sickness absence (LTSA), they could incorporate these risk assessments into their patient management plans and cooperate more with occupational physicians to prevent LTSA. To evaluate the effectiveness of a protocol helping GPs in recording risks of LTSA and in co-operating with occupational physicians (OPs). Twenty-six GPs (co-operating in four groups) in Amsterdam, The Netherlands, participated in a controlled intervention study. Fourteen GPs were the protocol-supported intervention group and twelve GPs were the reference group. Outcome measures were consultations containing work-related information, information about two risk factors for LTSA, referrals to OPs and contacts of OPs with GPs and patients. Outcomes were identified through an electronic search in the GPs' information systems. Entries containing information were independently scored by two investigators. The proportions of patients with consultations documenting LTSA-pertinent items were compared between the groups, accounting for differences at baseline. There was no increase in consultations containing work-related information. Recording of risk factor information increased in the intervention group; the difference was 4.5% [95% CI 1.5-7.6] and 1.8% (95% CI -0.8 to 4.4) for the two risk factors. The referral rate to the OP increased by 2.9% (95% CI 1.2-4.5). There was no effect on contacts of OPs with GPs or with patients. Protocol-supported consultations may lead to a modest increase in information regarding two risk factors for LTSA in GPs' electronic records and to more referrals to OPs.

  18. Improvement in long-term ECMO by detailed monitoring of anticoagulation: a case report.

    Science.gov (United States)

    Sievert, Alicia; Uber, Walter; Laws, Stacey; Cochran, Joel

    2011-01-01

    The use of unfractionated heparin (UFH) as an anticoagulant during long-term extracorporeal support presents a unique challenge for the clinician in balancing the amount of anticoagulant to maintain adequate anticoagulation without causing excessive bleeding. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) are the most common modality to monitor UFH on extracorporeal membrane oxygenation (ECMO). Limitations to these tests include consumptive coagulopathies, clotting factor deficiencies, platelet dysfunction, and fibrinolysis. The following case report describes the use of alternative monitoring strategies to assess more accurately anticoagulation during ECMO. A 20-month-old female presented to the emergency department with a 5-6 day history of cough, fever, tachypnea, and respiratory distress. She was diagnosed with influenza A and B with pneumonia. The patient was placed on veno-venous ECMO (V-V ECMO) after mechanical ventilation failed. On ECMO day eight, the patient developed a thrombus in her inferior vena cava and pleural effusions, obstructing cannula flow. Laboratory tests revealed the ACT was within range, yet the aPTT was dropping, despite increased heparin. Heparin levels were low and antithrombin-III (AT) concentrations were 40%. Recombinant AT was given and subsequent aPTTs were within the therapeutic range. Later, the aPTT decreased to 475 mg/ dL, and Factor VIII >150 IU/dL, suggesting an acute phase reaction or ongoing systemic inflammation, increasing the risk for thrombosis. We maintained heparin assays between 0.5-0.7 IU/mL and AT >60% to assure heparin's effect. The patient showed no signs of excess bleeding, blood product administration, or clots in the circuit, suggesting proper anticoagulation. The patient was successfully weaned on day 33 and is currently alive and at home. Monitoring of anti-Xa UFH and AT proved effective for measuring anticoagulation and detecting inconsistencies in other anticoagulation

  19. Changes in gene expression caused by insect venom immunotherapy responsible for the long-term protection of insect venom-allergic patients.

    Science.gov (United States)

    Niedoszytko, Marek; Bruinenberg, Marcel; de Monchy, Jan; Weersma, Rinse K; Wijmenga, Cisca; Jassem, Ewa; Elberink, Joanne N G Oude

    2011-06-01

    Insect venom immunotherapy (VIT) is the only causative treatment of insect venom allergy (IVA). The immunological mechanism(s) responsible for long-term protection achieved by VIT are largely unknown. A better understanding is relevant for improving the diagnosis, prediction of anaphylaxis, and monitoring and simplifying treatment of IVA. To find genes that are differentially expressed during the maintenance phase of VIT and after stopping, to get clues about the pathways involved in the long-term protective effect of immunotherapy. Whole genome gene expression analysis was performed on RNA samples from 50 patients treated with VIT and 43 healthy controls. Patients were divided into three groups: (1) before the start of VIT; (2) on maintenance phase of VIT for at least 3 years still receiving injections; and (3) after VIT. Of all 48,804 probes present in the array, 48,773 transcripts had sufficient data for further analysis. The list of genes that were differentially expressed (at least log2 FC > 2; P Immunology. Published by Elsevier Inc. All rights reserved.

  20. Preliminary study of an exercise programme for reducing fatigue and improving sleep among long-term haemodialysis patients

    Science.gov (United States)

    Maniam, Radha; Subramanian, Pathmawathi; Singh, Surindar Kaur Surat; Lim, Soo Kun; Chinna, Karuthan; Rosli, Roshaslina

    2014-01-01

    INTRODUCTION Fatigue and quality of sleep are the main factors that contribute to a poor quality of life among patients on long-term haemodialysis. Studies have also emphasised the importance of exercise for improving the wellbeing of dialysis patients. This study aimed to determine the effectiveness of a predialysis low-to-moderate-intensity exercise programme for reducing fatigue and improving sleep disorders among long-term haemodialysis patients. METHODS In this quasi-experimental study, an exercise programme was conducted three times a week for 12 weeks before long-term haemodialysis patients underwent dialysis at two centres. The patients were categorised into either the exercise group (n = 28) or control group (n = 27). The latter was asked to maintain their current lifestyles. Assessments of fatigue and sleep disorder levels were performed for both groups using self-reported questionnaires at baseline and after intervention. The patients’ perception of the exercise programme was also determined using self-reported questionnaires. RESULTS Paired sample t-test indicated improvements in fatigue level in the exercise group (mean fatigue score: post-treatment 40.5 ± 7.9 vs. pre-treatment 30.0 ± 10.9). Improvements in sleep disorders were also observed in the exercise group (mean score: post-treatment 7.6 ± 3.3 vs. pre-treatment 10.1 ± 3.8). However, sleep quality deteriorated in the control group (mean score: post-treatment 10.7 ± 2.9 vs. pre-treatment 9.3 ± 2.9). CONCLUSION Simple low-to-moderate-intensity exercise is effective for improving fatigue, sleep disorders and the overall quality of life among haemodialysis patients. PMID:25273932

  1. Shifting the Paradigm for Long Term Monitoring at Legacy Sites to Improve Performance while Reducing Costs - 13422

    International Nuclear Information System (INIS)

    Eddy-Dilek, Carol A; Looney, Brian B.; Gaughan, Thomas; Kmetz, Thomas; Seaman, John

    2013-01-01

    A major issue facing many government and private industry sites that were previously contaminated with radioactive and chemical wastes is that often the sites cannot be cleaned up enough to permit unrestricted human access. These sites will require long-term management, in some cases indefinitely, leaving site owners with the challenge of protecting human health and environmental quality in a cost effective manner. Long-term monitoring of groundwater contamination is one of the largest projected costs in the life cycle of environmental management at the Savannah River Site (SRS), the larger DOE complex, and many large federal and private sites. Currently, most monitoring strategies are focused on laboratory measurements of contaminants measured in groundwater samples collected from wells. This approach is expensive, and provides limited and lagging information about the effectiveness of cleanup activities and the behavior of the residual contamination. Over the last twenty years, DOE and other federal agencies have made significant investments in the development of various types of sensors and strategies that would allow for remote analysis of contaminants in groundwater, but these approaches do not promise significant reductions in risk or cost. Scientists at SRS have developed a new paradigm to simultaneously improve the performance of long term monitoring systems while lowering the overall cost of monitoring. This alternative approach incorporates traditional point measurements of contaminant concentration with measurements of controlling variables including boundary conditions, master variables, and traditional plume/contaminant variables. Boundary conditions are the overall driving forces that control plume movement and therefore provide leading indication to changes in plume stability. These variables include metrics associated with meteorology, hydrology, hydrogeology, and land use. Master variables are the key variables that control the chemistry of the

  2. Short- and long-term changes in sugarbeet (Beta vulgaris L. gene expression due to postharvest jasmonic acid treatment - Data

    Directory of Open Access Journals (Sweden)

    Lucilene Silva de Oliveira

    2017-04-01

    Full Text Available Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L. root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to water-treated controls, unigene annotations against nonredundant (Nr, Swiss-Prot, Clusters of Orthologous Groups (COG, and Kyoto Encyclopedia of Genes and Genomes (KEGG protein databases, and unigene annotations with Gene Ontology (GO terms. Putative defense unigenes are compiled and annotated against the sugarbeet genome. Differential gene expression data were generated by RNA sequencing. Interpretation of the data is available in the research article, “Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots” (K.K. Fugate, L.S. Oliveira, J.P. Ferrareze, M.D. Bolton, E.L. Deckard, F.L. Finger, 2017 [1]. Public dissemination of this dataset will allow further analyses of the data.

  3. Long-term effects of di-octyl phthalate on the expression of immune-related genes in Tegillarca granosa

    Science.gov (United States)

    Wang, Ji; Li, Ye; Dai, Juan; Su, Xiurong; Li, Chenghua; Shen, Lingling

    2016-05-01

    Di-octyl phthalate (DOP) is widely used as a plasticizer in the plastics industry. As a result, DOP is often found in marine water ecosystems where many species are exposed to it. Our objective was to evaluate the effect of long-term (14 d) DOP exposure (2.6, 7.8, or 31.2 mg/L) on the expression of immunerelated genes in Tegillarca granosa. The expression of small heat shock protein (sHSPs) and tissue inhibitor of metalloproteinase (TIMP) were highest in clams exposed to 31.2 mg/L DOP on days 7 and 14. The relative expression of Tg-ferritin, superoxide dismutase (SOD), and metallothionein (MT) increased initially then decreased as the concentration of DOP increased. The hemoglobin of T. granosa (Tg-HbI) exhibited two distinct expression patterns at two time points. Our results suggest that the immune response of T. granosa against DOP pollution varies depending on the dose. Additionally, we identified some immune-related genes that are promising candidates for biomarkers of DOP.

  4. Long-term mortality rates (>8-year) improve as compared to the general and obese population following bariatric surgery.

    Science.gov (United States)

    Telem, Dana A; Talamini, Mark; Shroyer, A Laurie; Yang, Jie; Altieri, Maria; Zhang, Qiao; Gracia, Gerald; Pryor, Aurora D

    2015-03-01

    Sparse data are available on long-term patient mortality following bariatric surgery as compared to the general population. The purpose of this study was to assess long-term mortality rates and identify risk factors for all-cause mortality following bariatric surgery. New York State (NYS) Planning and Research Cooperative System (SPARCS) longitudinal administrative data were used to identify 7,862 adult patients who underwent a primary laparoscopic bariatric surgery from 1999 to 2005. The Social Security Death Index database identified >30-day mortalities. Risk factors for mortality were screened using a univariate Cox proportional hazard (PH) model and analyzed using a multiple PH model. Based on age, gender, and race/ethnicity, actuarial projections for NYS mortality rates obtained from Centers of Disease Control were compared to the actual post-bariatric surgery mortality rates observed. The mean bariatric mortality rate was 2.5 % with 8-14 years of follow-up. Mean time to death ranged from 4 to 6 year and did not differ by operation (p = 0.073). From 1999 to 2010, the actuarial mortality rate predicted for the general NYS population was 2.1 % versus the observed 1.5 % for the bariatric surgery population (p = 0.005). Extrapolating to 2013, demonstrated the actuarial mortality predictions at 3.1 % versus the bariatric surgery patients' observed morality rate of 2.5 % (p = 0.01). Risk factors associated with an earlier time to death included: age, male gender, Medicare/Medicaid insurance, congestive heart failure, rheumatoid arthritis, pulmonary circulation disorders, and diabetes. No procedure-specific or perioperative complication impact for time-to-death was found. Long-term mortality rate of patients undergoing bariatric surgery significantly improves as compared to the general population regardless of bariatric operation performed. Additionally, perioperative complications do not increase long-term mortality risk. This study did identify specific patient

  5. Factors influencing the long-term sustainment of quality improvements made in addiction treatment facilities: a qualitative study

    Directory of Open Access Journals (Sweden)

    Scott P. Stumbo

    2017-11-01

    Full Text Available Abstract Background A greater understanding of the factors that influence long-term sustainment of quality improvement (QI initiatives is needed to promote organizational ability to sustain QI practices over time, help improve future interventions, and increase the value of QI investments. Methods We approached 83 of 201 executive sponsors or change leaders at addiction treatment organizations that participated in the 2007–2009 NIATx200 QI intervention. We completed semi-structured interviews with 33 individuals between November 2015 and April 2016. NIATx200 goals were to decrease wait time, increase admissions and improve retention in treatment. Interviews sought to understand factors that either facilitated or impeded long-term sustainment of organizational QI practices made during the intervention. We used thematic analysis to organize the data and group patterns of responses. We assessed available quantitative outcome data and intervention engagement data to corroborate qualitative results. Results We used narrative analysis to group four important themes related to long-term sustainment of QI practices: (1 finding alignment between business- and client-centered practices; (2 staff engagement early in QI process added legitimacy which facilitated sustainment; (3 commitment to integrating data into monitoring practices and the identification of a data champion; and (4 adequate organizational human resources devoted to sustainment. We found four corollary factors among agencies which did not sustain practices: (1 lack of evidence of impact on business practices led to discontinuation; (2 disengaged staff and lack of organizational capacity during implementation period led to lack of sustainment; (3 no data integration into overall business practices and no identified data champion; and (4 high staff turnover. In addition, we found that many agencies’ current use of NIATx methods and tools suggested a legacy effect that might improve

  6. Factors influencing the long-term sustainment of quality improvements made in addiction treatment facilities: a qualitative study.

    Science.gov (United States)

    Stumbo, Scott P; Ford, James H; Green, Carla A

    2017-11-01

    A greater understanding of the factors that influence long-term sustainment of quality improvement (QI) initiatives is needed to promote organizational ability to sustain QI practices over time, help improve future interventions, and increase the value of QI investments. We approached 83 of 201 executive sponsors or change leaders at addiction treatment organizations that participated in the 2007-2009 NIATx200 QI intervention. We completed semi-structured interviews with 33 individuals between November 2015 and April 2016. NIATx200 goals were to decrease wait time, increase admissions and improve retention in treatment. Interviews sought to understand factors that either facilitated or impeded long-term sustainment of organizational QI practices made during the intervention. We used thematic analysis to organize the data and group patterns of responses. We assessed available quantitative outcome data and intervention engagement data to corroborate qualitative results. We used narrative analysis to group four important themes related to long-term sustainment of QI practices: (1) finding alignment between business- and client-centered practices; (2) staff engagement early in QI process added legitimacy which facilitated sustainment; (3) commitment to integrating data into monitoring practices and the identification of a data champion; and (4) adequate organizational human resources devoted to sustainment. We found four corollary factors among agencies which did not sustain practices: (1) lack of evidence of impact on business practices led to discontinuation; (2) disengaged staff and lack of organizational capacity during implementation period led to lack of sustainment; (3) no data integration into overall business practices and no identified data champion; and (4) high staff turnover. In addition, we found that many agencies' current use of NIATx methods and tools suggested a legacy effect that might improve quality elsewhere, even absent overall sustainment of

  7. Accelerated long-term forgetting in temporal lobe epilepsy: evidence of improvement after left temporal pole lobectomy.

    Science.gov (United States)

    Gallassi, Roberto; Sambati, Luisa; Poda, Roberto; Stanzani Maserati, Michelangelo; Oppi, Federico; Giulioni, Marco; Tinuper, Paolo

    2011-12-01

    Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

    OpenAIRE

    Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

    2016-01-01

    Myotonic dystrophy type 1, also known as Steinert′s disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and periphe...

  9. Riding The Waves Of Quality Improvement : Sustainability and spread in a Dutch quality improvement program for long-term care

    NARCIS (Netherlands)

    S.S. Slaghuis (Sarah)

    2016-01-01

    markdownabstractIncreasingly, sustainability and spread have become part and parcel of organizational strategy in health care. This applies in particular to organizations in the long-term care sector, which faces an increasing care demand, ageing population and labor shortage. Unfortunately,

  10. Variations in gene and protein expression in canine chondrodystrophic nucleus pulposus cells following long-term three-dimensional culture.

    Directory of Open Access Journals (Sweden)

    Munetaka Iwata

    Full Text Available Intervertebral disc (IVD degeneration greatly affects quality of life. The nucleus pulposus (NP of chondrodystrophic dog breeds (CDBs is similar to the human NP, because the cells disappear with age and are replaced by fibrochondrocyte-like cells. However, because IVD develops as early as within the first year of life, we used canines as a model to investigate in vitro the mechanisms underlying IVD degeneration. Specifically, we evaluated the potential of a three-dimensional (3D culture of healthy NP as an in vitro model system to investigate the mechanisms of IVD degeneration. Agarose hydrogels were populated with healthy NP cells from beagles after performing magnetic resonance imaging, and mRNA expression profiles and pericellular extracellular matrix (ECM protein distribution were determined. After 25 days of 3D culture, there was a tendency for redifferentiation into the native NP phenotype, and mRNA levels of Col2A1, COMP, and CK18 were not significantly different from those of freshly isolated cells. Our findings suggest that long-term 3D culture promoted chondrodystrophic NP redifferentiation through reconstruction of the pericellular microenvironment. Further, lipopolysaccharide (LPS induced expression of TNF-α, MMP3, MMP13, VEGF, and PGES mRNA in the 3D cultures, creating a molecular milieu that mimics that of degenerated NP. These results suggest that this in vitro model represents a reliable and cost-effective tool for evaluating new therapies for disc degeneration.

  11. Using client experiences for quality improvement in long-term care organizations

    NARCIS (Netherlands)

    Zuidgeest, M.; Strating, M.; Luijkx, K.; Westert, G.P.; Delnoij, E.D.

    2012-01-01

    OBJECTIVE: To examine whether client experiences measured with the Consumer Quality Index (CQ-index or CQI) questionnaires are used in Dutch nursing homes and homes for the elderly for quality improvement. DESIGN: Information was gathered through face-to-face interviews with day-to-day workers,

  12. Improving acute and long-term myocardial infarction care : bridging the gap between science and practice

    NARCIS (Netherlands)

    Liem, Su-San

    2009-01-01

    The main topic of this thesis was the design, implementation and subsequent evaluation of an all-phases integrated care program for patients with acute myocardial infarction: the MISSION! protocol. The aim of MISSION! was to improve daily care for patients with an acute myocardial infarction by

  13. Improving food and fluid intake for older adults living in long-term care

    DEFF Research Database (Denmark)

    Keller, Heather; Beck, Anne Marie; Namasivayam, Ashwini

    2015-01-01

    intake for persons living in LTC. Top determinants to address with intervention research included social interactions of residents at mealtime; self-feeding ability; the dining environment; the attitudes, knowledge, and skills of staff; adequate time to eat/availability of staff to provide assistance...... for the development and testing of interventions to improve food and fluid intake of older adults living in LTC....

  14. A novel stent inflation protocol improves long-term outcomes compared with rapid inflation/deflation deployment method.

    Science.gov (United States)

    Vallurupalli, Srikanth; Kasula, Srikanth; Kumar Agarwal, Shiv; Pothineni, Naga Venkata K; Abualsuod, Amjad; Hakeem, Abdul; Ahmed, Zubair; Uretsky, Barry F

    2017-08-01

    High-pressure inflation for coronary stent deployment is universally performed. However, the duration of inflation is variable and does not take into account differences in lesion compliance. We developed a standardized "pressure optimization protocol" (POP) using inflation pressure stability rather than an arbitrary inflation time or angiographic balloon appearance for stent deployment. Whether this approach improves long-term outcomes is unknown. 792 patients who underwent PCI using either rapid inflation/deflation (n = 376) or POP (n = 416) between January 2009 and March 2014 were included. Exclusion criteria included PCI for acute myocardial infarction, in-stent restenosis, chronic total occlusion, left main, and saphenous vein graft lesions. Primary endpoint was target vessel failure [TVF = combined end point of target vessel revascularization (TVR), myocardial infarction, and cardiac death]. Outcomes were analyzed in the entire cohort and in a propensity analysis. Stent implantation using POP with a median follow-up of 1317 days was associated with lower TVF compared with rapid inflation/deflation (10.1 vs. 17.8%, P inflation/deflation (10 vs. 18%, P < 0.0001). Stent deployment using POP led to reduced TVF compared to rapid I/D. These results recommend this method to improve long-term outcomes. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Improved Reliability of SiC Pressure Sensors for Long Term High Temperature Applications

    Science.gov (United States)

    Okojie, R. S.; Nguyen, V.; Savrun, E.; Lukco, D.

    2011-01-01

    We report advancement in the reliability of silicon carbide pressure sensors operating at 600 C for extended periods. The large temporal drifts in zero pressure offset voltage at 600 C observed previously were significantly suppressed to allow improved reliable operation. This improvement was the result of further enhancement of the electrical and mechanical integrity of the bondpad/contact metallization, and the introduction of studded bump bonding on the pad. The stud bump contact promoted strong adhesion between the Au bond pad and the Au die-attach. The changes in the zero offset voltage and bridge resistance over time at temperature were explained by the microstructure and phase changes within the contact metallization, that were analyzed with Auger electron spectroscopy (AES) and field emission scanning electron microscopy (FE-SEM).

  16. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics

    Directory of Open Access Journals (Sweden)

    Enzo Grossi

    2016-08-01

    Full Text Available Objectives: Autism spectrum disorder is a neurodevelopmental condition that typically displays socio-communicative impairment as well as restricted stereotyped interests and activities, in which gastrointestinal disturbances are commonly reported. We report the case of a boy with Autism Spectrum Disorder (ASD diagnosis, severe cognitive disability and celiac disease in which an unexpected improvement of autistic core symptoms was observed after four months of probiotic treatment. Method: The case study refers to a 12 years old boy with ASD and severe cognitive disability attending the Villa Santa Maria Institute in resident care since 2009. Diagnosis of ASDs according to DSM-V criteria was confirmed by ADOS-2 assessment (Autism Diagnostic Observation Schedule. The medication used was VSL#3, a multi-strain mixture of ten probiotics. The treatment lasted 4 weeks followed by a four month follow-up. The rehabilitation program and the diet was maintained stable in the treatment period and in the follow up. ADOS-2 was assessed six times: two times before starting treatment; two times during the treatment and two times after interruption of the treatment. Results: The probiotic treatment reduced the severity of abdominal symptoms as expected but an improvement in Autistic core symptoms was unexpectedly clinically evident already after few weeks from probiotic treatment start. The score of Social Affect domain of ADOS improved changing from 20 to 18 after two months treatment with a further reduction of 1 point in the following two months. The level 17 of severity remained stable in the follow up period. It is well known that ADOS score does not fluctuate spontaneously along time in ASD and is absolutely stable. Conclusions: The appropriate use of probiotics deserves further research, which hopefully will open new avenues in the fight against ASD.

  17. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics.

    Science.gov (United States)

    Grossi, Enzo; Melli, Sara; Dunca, Delia; Terruzzi, Vittorio

    2016-01-01

    Autism spectrum disorder is a neurodevelopmental condition that typically displays socio-communicative impairment as well as restricted stereotyped interests and activities, in which gastrointestinal disturbances are commonly reported. We report the case of a boy with Autism Spectrum Disorder (ASD) diagnosis, severe cognitive disability and celiac disease in which an unexpected improvement of autistic core symptoms was observed after four months of probiotic treatment. The case study refers to a 12 years old boy with ASD and severe cognitive disability attending the Villa Santa Maria Institute in resident care since 2009. Diagnosis of ASDs according to DSM-V criteria was confirmed by ADOS-2 assessment (Autism Diagnostic Observation Schedule). The medication used was VSL#3, a multi-strain mixture of ten probiotics. The treatment lasted 4 weeks followed by a four month follow-up. The rehabilitation program and the diet was maintained stable in the treatment period and in the follow up. ADOS-2 was assessed six times: two times before starting treatment; two times during the treatment and two times after interruption of the treatment. The probiotic treatment reduced the severity of abdominal symptoms as expected but an improvement in Autistic core symptoms was unexpectedly clinically evident already after few weeks from probiotic treatment start. The score of Social Affect domain of ADOS improved changing from 20 to 18 after two months treatment with a further reduction of 1 point in the following two months. The level 17 of severity remained stable in the follow up period. It is well known that ADOS score does not fluctuate spontaneously along time in ASD and is absolutely stable. The appropriate use of probiotics deserves further research, which hopefully will open new avenues in the fight against ASD.

  18. Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries

    DEFF Research Database (Denmark)

    Dalsgaard, T.; Mortensen, Alicja; Larsen, C. R.

    2003-01-01

    arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings...... in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated. Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E-max, percentage of precontraction) in proximal coronary arteries (45.8 +/- 9.6% vs. 24.1 +/- 3.7%, p ....05). In the same artery segment, 17β-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100 +/- 7% vs. 132 +/- 11%, p

  19. An improved non-Markovian degradation model with long-term dependency and item-to-item uncertainty

    Science.gov (United States)

    Xi, Xiaopeng; Chen, Maoyin; Zhang, Hanwen; Zhou, Donghua

    2018-05-01

    It is widely noted in the literature that the degradation should be simplified into a memoryless Markovian process for the purpose of predicting the remaining useful life (RUL). However, there actually exists the long-term dependency in the degradation processes of some industrial systems, including electromechanical equipments, oil tankers, and large blast furnaces. This implies the new degradation state depends not only on the current state, but also on the historical states. Such dynamic systems cannot be accurately described by traditional Markovian models. Here we present an improved non-Markovian degradation model with both the long-term dependency and the item-to-item uncertainty. As a typical non-stationary process with dependent increments, fractional Brownian motion (FBM) is utilized to simulate the fractal diffusion of practical degradations. The uncertainty among multiple items can be represented by a random variable of the drift. Based on this model, the unknown parameters are estimated through the maximum likelihood (ML) algorithm, while a closed-form solution to the RUL distribution is further derived using a weak convergence theorem. The practicability of the proposed model is fully verified by two real-world examples. The results demonstrate that the proposed method can effectively reduce the prediction error.

  20. Improving forecasting accuracy of medium and long-term runoff using artificial neural network based on EEMD decomposition.

    Science.gov (United States)

    Wang, Wen-chuan; Chau, Kwok-wing; Qiu, Lin; Chen, Yang-bo

    2015-05-01

    Hydrological time series forecasting is one of the most important applications in modern hydrology, especially for the effective reservoir management. In this research, an artificial neural network (ANN) model coupled with the ensemble empirical mode decomposition (EEMD) is presented for forecasting medium and long-term runoff time series. First, the original runoff time series is decomposed into a finite and often small number of intrinsic mode functions (IMFs) and a residual series using EEMD technique for attaining deeper insight into the data characteristics. Then all IMF components and residue are predicted, respectively, through appropriate ANN models. Finally, the forecasted results of the modeled IMFs and residual series are summed to formulate an ensemble forecast for the original annual runoff series. Two annual reservoir runoff time series from Biuliuhe and Mopanshan in China, are investigated using the developed model based on four performance evaluation measures (RMSE, MAPE, R and NSEC). The results obtained in this work indicate that EEMD can effectively enhance forecasting accuracy and the proposed EEMD-ANN model can attain significant improvement over ANN approach in medium and long-term runoff time series forecasting. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Improving simulated long-term responses of vegetation to temperature and precipitation extremes using the ACME land model

    Science.gov (United States)

    Ricciuto, D. M.; Warren, J.; Guha, A.

    2017-12-01

    While carbon and energy fluxes in current Earth system models generally have reasonable instantaneous responses to extreme temperature and precipitation events, they often do not adequately represent the long-term impacts of these events. For example, simulated net primary productivity (NPP) may decrease during an extreme heat wave or drought, but may recover rapidly to pre-event levels following the conclusion of the extreme event. However, field measurements indicate that long-lasting damage to leaves and other plant components often occur, potentially affecting the carbon and energy balance for months after the extreme event. The duration and frequency of such extreme conditions is likely to shift in the future, and therefore it is critical for Earth system models to better represent these processes for more accurate predictions of future vegetation productivity and land-atmosphere feedbacks. Here we modify the structure of the Accelerated Climate Model for Energy (ACME) land surface model to represent long-term impacts and test the improved model against observations from experiments that applied extreme conditions in growth chambers. Additionally, we test the model against eddy covariance measurements that followed extreme conditions at selected locations in North America, and against satellite-measured vegetation indices following regional extreme events.

  2. Long-term dietary restriction up-regulates activity and expression of renal arginase II in aging mice.

    Science.gov (United States)

    Majaw, T; Sharma, R

    2017-06-01

    Arginase II is a mitochondrial enzyme that catalyses the hydrolysis of L-arginine into urea and ornithine. It is present in other extra-hepatic tissues that lack urea cycle. Therefore, it is plausible that arginase II has a physiological role other than urea cycle which includes polyamine, proline, glutamate synthesis and regulation of nitric oxide production. The high expression of arginase II in kidney, among extrahepatic tissues, might have an important role associated with kidney functions. The present study is aimed to determine the age-associated alteration in the activity and expression of arginase II in the kidney of mice of different ages. The effect of dietary restriction to modulate the agedependent changes of arginase II was also studied. Results showed that renal arginase II activity declines significantly with the progression of age (p less than 0.01 and p less than 0.001 in 6- and 18-month-old mice, respectively as compared to 2-month old mice) and is due to the reduction in its protein as well as the mRNA level (p less than 0.001 in both 6- and 18-month-old mice as compared to 2-month-old mice). Long-term dietary restriction for three months has significantly up-regulated arginase II activity and expression level in both 2- and 18-month-old mice (p less than 0.01 and p less than 0.001, respectively as compared to AL group). These findings clearly indicate that the reducing level of arginase II during aging might have an impact on the declining renal functions. This age-dependent down-regulation of arginase II in the kidney can be attenuated by dietary restriction which may help in the maintenance of such functions.

  3. Microarray analysis of gene expression patterns of high lycopene tomato generated from seeds after long-term space flight

    Science.gov (United States)

    Lu, Jinying; Ren, Chunxiao; Pan, Yi; Nechitailo, Galina S.; Liu, Min

    Lycopene content is a most vital trait of tomatoes due to the role of lycopene in reducing the risk of some kinds of cancers. In this experiment, we gained a high lycopene (hl) tomato (named HY-2), after seven generations of self-cross selection, from seeds Russian MNP-1 carried in Russia MIR space station for six years. HPLC result showed that the lycopene content was 1.6 times more than that in Russian MNP-1 (the wild type). Microarray analysis presented the general profile of differential expressed genes at the tomato developmental stage of 7DPB (days post breaker). One hundred and forty three differential expression genes were identified according to the following criterion: the average changes were no less than 1.5 folds with q-value (similar to FDR) less than 0.05 or changes were no less than 1.5 folds in all three biological replications. Most of the differential expressed genes were mainly involved in metabolism, response to stimulus, biosynthesis, development and regulation. Particularly, we discussed the genes involved in protein metabolism, response to unfolded protein, carotenoid biosynthesis and photosynthesis that might be related to the fruit development and the accumulation of lycopene. What's more, we conducted QRT-PCR validation of five key genes (Fps, CrtL-b, CrtR-b, Zep and Nxs) in the lycopene biosynthesis pathway through time courses and that provided the direct molecular evidence for the hl phenotype. Our results demonstrate that long-term space flight, as a rarely used tool, can positively cause some beneficial mutations in the seeds and thus to help to generate a high quality variety, combined with ground selections.

  4. Improving long term driving comfort by taking breaks - How break activity affects effectiveness.

    Science.gov (United States)

    Sammonds, George M; Mansfield, Neil J; Fray, Mike

    2017-11-01

    During long duration journeys, drivers are encouraged to take regular breaks. The benefits of breaks have been documented for safety; breaks may also be beneficial for comfort. The activity undertaken during a break may influence its effectiveness. Volunteers completed 3 journeys on a driving simulator. Each 130 min journey included a 10 min break after the first hour. During the break volunteers either stayed seated, left the simulator and sat in an adjacent room, or took a walk on a treadmill. The results show a reduction in driver discomfort during the break for all 3 conditions, but the effectiveness of the break was dependent on activity undertaken. Remaining seated in the vehicle provided some improvement in comfort, but more was experienced after leaving the simulator and sitting in an adjacent room. The most effective break occurred when the driver walked for 10 min on a treadmill. The benefits from taking a break continued until the end of the study (after a further hour of driving), such that comfort remained the best after taking a walk and worst for those who remained seated. It is concluded that taking a break and taking a walk is an effective method for relieving driving discomfort. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Guilt, shame and expressed emotion in carers of people with long-term mental health difficulties: A systematic review.

    Science.gov (United States)

    Cherry, Mary Gemma; Taylor, Peter James; Brown, Stephen Lloyd; Rigby, Jake Wilfred; Sellwood, William

    2017-03-01

    Expressed emotion (EE) is a global index of familial emotional climate, whose primary components are emotional over-involvement (EOI) and critical comments (CC)/hostility. There is a strong theoretical rationale for hypothesising that carers' guilt and shame may be differentially associated with their EOI and CC/hostility respectively. This systematic review investigates the magnitude of these theorised associations in carers of people with long-term mental health difficulties. Electronic searches (conducted in May 2016 across Medline, CINAHL, Embase, PsycINFO and ProQuest) were supplemented with iterative hand searches. Ten papers, reporting data from eight studies, were included. Risk of bias was assessed using a standardised checklist. Relevant data were extracted and synthesised narratively. EOI was positively associated with both guilt and shame, whereas CC/hostility was positively associated with shame. The strength of associations varied depending on whether or not guilt and shame were assessed within the context of the caring relationship. Based on these data, an argument can be made for the refinement, development and evaluation of systemic and individual interventions designed to target carers' guilt and shame. However, more research is needed to clarify the strength of these associations and their direction of effect before firm conclusions can be drawn. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    International Nuclear Information System (INIS)

    Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; Hart, Marieke van der; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

    2012-01-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

  7. Process-oriented guided-inquiry learning improves long-term retention of information.

    Science.gov (United States)

    Vanags, Thea; Pammer, Kristen; Brinker, Jay

    2013-09-01

    Many chemistry educators have adopted the process-oriented guided instructional learning (POGIL) pedagogy. However, it is not clear which aspects of POGIL are the most important in terms of actual learning. We compared 354 first-year undergraduate psychology students' learning in physiological psychology using four teaching methods: control, POGIL, POGIL without reporting [no report out (NRO)], and POGIL run by untrained graduate students [new facilitator (NF)]. Student activities were identical across POGIL variations and highly similar for control. Participants' knowledge was evaluated before (pretest), immediately after (posttest), and 2 wk later (followup). Control and POGIL groups showed no improvement at posttest, whereas NRO and NF groups both recalled more material than at pretest (P = 0.002 and P < 0.0005, respectively). In a surprise test 2 wk later, control (P < 0.0005), NRO (P = 0.03), and NF (P < 0.0005) groups recalled less than at posttest. The POGIL group showed the smallest drop in knowledge (P = 0.05). Importantly, the control group's knowledge was below pretest levels (P < 0.0005), whereas the POGIL, NRO, and NF groups' knowledge was not. Self-assessment of knowledge was consistent across groups at pretest, but POGIL participants had the lowest confidence at posttest and 2 wk later. At followup, the control, NRO, and NF groups showed greater confidence in their knowledge than the POGIL group (P = 0.03, P = 0.002, and P = 0.004, respectively). POGIL and its variations appear to consolidate existing knowledge against memory decay even when student confidence does not match performance.

  8. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    Energy Technology Data Exchange (ETDEWEB)

    Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Wisialowski, Todd A. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Cremers, Thomas; Hart, Marieke van der [Brains On-Line B.V., University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (Netherlands); Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States)

    2012-11-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

  9. Improving Long-term Post-wildfire hydrologic simulations using ParFlow

    Science.gov (United States)

    Lopez, S. R.; Kinoshita, A. M.

    2015-12-01

    Wildfires alter the natural hydrologic processes within a watershed. After vegetation is burned, the combustion of organic material and debris settles into the soil creating a hydrophobic layer beneath the soil surface with varying degree of thickness and depth. Vegetation regrowth rates vary as a function of radiative exposure, burn severity, and precipitation patterns. Hydrologic models used by the Burned Area Emergency Response (BAER) teams use input data and model calibration constraints that are generally either one-dimensional, empirically-based models, or two-dimensional, conceptually-based models with lumped parameter distributions. These models estimate runoff measurements at the watershed outlet; however, do not provide a distributed hydrologic simulation at each point within the watershed. This work uses ParFlow, a three-dimensional, distributed hydrologic model to (1) correlate burn severity with hydrophobicity, (2) evaluate vegetation recovery rate on water components, and (3) improve flood prediction for managers to help with resource allocation and management operations in burned watersheds. ParFlow is applied to Devil Canyon (43 km2) in San Bernardino, California, which was 97% burned in the 2003 Old Fire. The model set-up uses a 30m-cell size resolution over a 6.7 km by 6.4 km lateral extent. The subsurface reaches 30 m and is assigned a variable cell thickness. Variable subsurface thickness allows users to explicitly consider the degree of recovery throughout the stages of regrowth. Burn severity maps from remotely sensed imagery are used to assign initial hydrophobic layer parameters and thickness. Vegetation regrowth is represented with satellite an Enhanced Vegetation Index. Pre and post-fire hydrologic response is evaluated using runoff measurements at the watershed outlet, and using water component (overland flow, lateral flow, baseflow) measurements.

  10. Shifting the Paradigm for Long Term Monitoring at Legacy Sites to Improve Performance while Reducing Costs - 13422

    Energy Technology Data Exchange (ETDEWEB)

    Eddy-Dilek, Carol A; Looney, Brian B. [Savannah River National Laboratory (United States); Gaughan, Thomas; Kmetz, Thomas [Savannah River Nuclear Solutions, LLC (United States); Seaman, John [Savannah River Ecology Laboratory (United States)

    2013-07-01

    A major issue facing many government and private industry sites that were previously contaminated with radioactive and chemical wastes is that often the sites cannot be cleaned up enough to permit unrestricted human access. These sites will require long-term management, in some cases indefinitely, leaving site owners with the challenge of protecting human health and environmental quality in a cost effective manner. Long-term monitoring of groundwater contamination is one of the largest projected costs in the life cycle of environmental management at the Savannah River Site (SRS), the larger DOE complex, and many large federal and private sites. Currently, most monitoring strategies are focused on laboratory measurements of contaminants measured in groundwater samples collected from wells. This approach is expensive, and provides limited and lagging information about the effectiveness of cleanup activities and the behavior of the residual contamination. Over the last twenty years, DOE and other federal agencies have made significant investments in the development of various types of sensors and strategies that would allow for remote analysis of contaminants in groundwater, but these approaches do not promise significant reductions in risk or cost. Scientists at SRS have developed a new paradigm to simultaneously improve the performance of long term monitoring systems while lowering the overall cost of monitoring. This alternative approach incorporates traditional point measurements of contaminant concentration with measurements of controlling variables including boundary conditions, master variables, and traditional plume/contaminant variables. Boundary conditions are the overall driving forces that control plume movement and therefore provide leading indication to changes in plume stability. These variables include metrics associated with meteorology, hydrology, hydrogeology, and land use. Master variables are the key variables that control the chemistry of the

  11. Long-term persistence of quality improvements for an intensive care unit communication initiative using the VALUE strategy.

    Science.gov (United States)

    Wysham, Nicholas G; Mularski, Richard A; Schmidt, David M; Nord, Shirley C; Louis, Deborah L; Shuster, Elizabeth; Curtis, J Randall; Mosen, David M

    2014-06-01

    Communication in the intensive care unit (ICU) is an important component of quality ICU care. In this report, we evaluate the long-term effects of a quality improvement (QI) initiative, based on the VALUE communication strategy, designed to improve communication with family members of critically ill patients. We implemented a multifaceted intervention to improve communication in the ICU and measured processes of care. Quality improvement components included posted VALUE placards, templated progress note inclusive of communication documentation, and a daily rounding checklist prompt. We evaluated care for all patients cared for by the intensivists during three separate 3 week periods, pre, post, and 3 years following the initial intervention. Care delivery was assessed in 38 patients and their families in the pre-intervention sample, 27 in the post-intervention period, and 41 in follow-up. Process measures of communication showed improvement across the evaluation periods, for example, daily updates increased from pre 62% to post 76% to current 84% of opportunities. Our evaluation of this quality improvement project suggests persistence and continued improvements in the delivery of measured aspects of ICU family communication. Maintenance with point-of-care-tools may account for some of the persistence and continued improvements. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Gene expression profile in long-term non progressor HIV infected patients: in search of potential resistance factors.

    Science.gov (United States)

    Luque, Maria Carolina; Santos, Camila C; Mairena, Eliane C; Wilkinson, Peter; Boucher, Genèvieve; Segurado, Aluisio C; Fonseca, Luiz A; Sabino, Ester; Kalil, Jorge E; Cunha-Neto, Edecio

    2014-11-01

    Long-term non-progressors (LTNP) represent a minority (1-5%) of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm(3) and low viremia in the absence of antiretroviral treatment. Protective factors described so far such as the CCR5delta32 deletion, protective HLA alleles, or defective viruses fail to fully explain the partial protection phenotype. The existence of additional host resistance mechanisms in LTNP patients was investigated here using a whole human genome microarray study comparing gene expression profiles of unstimulated peripheral blood mononuclear cells from LTNP patients, HIV-1 infected patients under antiretroviral therapy with CD4+ T cell levels above 500/mm(3) (ST), as well as healthy individuals. Genes that were up- or downregulated exclusively in LTNP, ST or in both groups in comparison to controls were identified and classified in functional categories using Ingenuity Pathway Analysis. ST and LTNP patient groups revealed distinct genetic profiles, regarding gene number in each category and up- or downregulation of specific genes, which could have a bearing on the outcome of each group. We selected some relevant genes to validate the differential expression using quantitative real-time qRT-PCR. Among others, we found several genes related to the canonical Wnt/beta-catenin signaling pathway. Our results identify new possible host genes and molecules that could be involved in the mechanisms leading to the slower progression to AIDS and sustained CD4+ T cell counts that is peculiar to LTNP patients. Copyright © 2014. Published by Elsevier Ltd.

  13. Differentially expressed genes linked to natural variation in long-term memory formation in Cotesia parasitic wasps

    Directory of Open Access Journals (Sweden)

    Joke J. F. A. Van Vugt

    2015-09-01

    Full Text Available Even though learning and memory are universal traits in the Animal Kingdom, closely related species reveal substantial variation in learning rate and memory dynamics. To determine the genetic background of this natural variation, we studied two congeneric parasitic wasp species, Cotesia glomerata and C. rubecula, which lay their eggs in caterpillars of the large and small cabbage white butterfly. A successful egg laying event serves as an unconditioned stimulus in a classical conditioning paradigm, where plant odors become associated to the encounter of a suitable host caterpillar. Depending on the host species, the number of conditioning trials and the parasitic wasp species, three different types of transcription-dependent long-term memory (LTM and one type of transcription-independent, anesthesia-resistant memory (ARM can be distinguished. To identify transcripts underlying these differences in memory formation, we isolated mRNA from parasitic wasp heads at three different time points between induction and consolidation of each of the four memory types, and for each sample three biological replicates, where after strand-specific paired-end 100 bp deep sequencing. Transcriptomes were assembled de novo and differential expression was determined for each memory type and time point after conditioning, compared to unconditioned wasps. Most differentially expressed (DE genes and antisense transcripts were only DE in one of the LTM types. Among the DE genes that were DE in two or more LTM types, were many protein kinases and phosphatases, small GTPases, receptors and ion channels. Some genes were DE in opposing directions between any of the LTM memory types and ARM, suggesting that ARM in Cotesia requires the transcription of genes inhibiting LTM or vice versa. We discuss our findings in the context of neuronal functioning, including RNA splicing and transport, epigenetic regulation, neurotransmitter/peptide synthesis and antisense transcription. In

  14. Genome-Wide Expression Analysis of Reactive Oxygen Species Gene Network in Mizuna Plants Grown in Long-Term Spaceflight

    Science.gov (United States)

    Sugimoto, Manabu; Gusev, Oleg; Wheeler, Raymond; Levinskikh, Margarita; Sychev, Vladimir; Bingham, Gail; Hummerick, Mary; Oono, Youko; Matsumoto, Takashi; Yazawa, Takayuki

    We have developed a plant growth system, namely Lada, which was installed in ISS to study and grow plants, including vegetables in a spaceflight environment. We have succeeded in cultivating Mizuna, tomato, pea, radish, wheat, rice, and barley in long-term spaceflight. Transcription levels of superoxide dismutase, glutamyl transferase, catalase, and ascorbate peroxidase were increased in the barley germinated and grown for 26 days in Lada, though the whole-plant growth and development of the barley in spaceflight were the same as in the ground control barley. In this study, we investigated the response of the ROS gene network in Mizuna, Brassica rapa var. nipposinica, cultivated under spaceflight condition. Seeds of Mizuna were sown in the root module of LADA aboard the Zvezda module of ISS and the seedlings were grown under 24h lighting in the leaf chamber. After 27 days of cultivation, the plants were harvested and stored at -80(°) C in MELFI aboard the Destiny module, and were transported to the ground at < -20(°) C in GLACIER aboard Space Shuttle. Ground control cultivation was carried out under the same conditions in LADA. Total RNA isolated from leaves was subjected to mRNA-Seq using next generation sequencing (NGS) technology. A total of 20 in 32 ROS oxidative marker genes were up-regulated, including high expression of four hallmarks, and preferentially expressed genes associated with ROS-scavenging including thioredoxin, glutaredoxin, and alternative oxidase genes. In the transcription factors of the ROS gene network, MEKK1-MKK4-MPK3, OXI1-MKK4-MPK3, and OXI1-MPK3 of MAP cascades, induction of WRKY22 by MEKK1-MKK4-MPK3 cascade, induction of WRKY25 and repression of Zat7 by Zat12 were suggested. These results revealed that the spaceflight environment induced oxidative stress and the ROS gene network activation in the space-grown Mizuna.

  15. Does early change predict long-term (6 months) improvements in subjects who receive manual therapy for low back pain?

    Science.gov (United States)

    Cook, Chad; Petersen, Shannon; Donaldson, Megan; Wilhelm, Mark; Learman, Ken

    2017-09-01

    Early change is commonly assessed for manual therapy interventions and has been used to determine treatment appropriateness. However, current studies have only explored the relationship of between or within-session changes and short-/medium-term outcomes. The goal of this study was to determine whether pain changes after two weeks of pragmatic manual therapy could predict those participants with chronic low back pain who demonstrate continued improvements at 6-month follow-up. This study was a retrospective observational design. Univariate logistic regression analyses were performed using a 33% and a 50% pain change to predict improvement. Those who experienced a ≥33% pain reduction by 2 weeks had 6.98 (95% CI = 1.29, 37.53) times higher odds of 50% improvement on the GRoC and 4.74 (95% CI = 1.31, 17.17) times higher odds of 50% improvement on the ODI (at 6 months). Subjects who reported a ≥50% pain reduction at 2 weeks had 5.98 (95% CI = 1.56, 22.88) times higher odds of a 50% improvement in the GRoC and 3.99 (95% CI = 1.23, 12.88) times higher odds of a 50% improvement in the ODI (at 6 months). Future studies may investigate whether a change in plan of care is beneficial for patients who are not showing early improvement predictive of a good long-term outcome.

  16. Data for improvement and clinical excellence: protocol for an audit with feedback intervention in long-term care

    Directory of Open Access Journals (Sweden)

    Schalm Corinne

    2010-10-01

    Full Text Available Abstract Background There is considerable evidence about the effectiveness of audit coupled with feedback, although few audit with feedback interventions have been conducted in long-term care (LTC settings to date. In general, the effects have been found to be modest at best, although in settings where there has been little history of audit and feedback, the effects may be greater, at least initially. The primary purpose of the Data for Improvement and Clinical Excellence (DICE Long-Term Care project is to assess the effects of an audit with feedback intervention delivered monthly over 13 months in four LTC facilities. The research questions we addressed are: 1. What effects do feedback reports have on processes and outcomes over time? 2. How do different provider groups in LTC and home care respond to feedback reports based on data targeted at improving quality of care? Methods/design The research team conducting this study comprises researchers and decision makers in continuing care in the province of Alberta, Canada. The intervention consists of monthly feedback reports in nine LTC units in four facilities in Edmonton, Alberta. Data for the feedback reports comes from the Resident Assessment Instrument Minimum Data Set (RAI version 2.0, a standardized instrument mandated for use in LTC facilities throughout Alberta. Feedback reports consist of one page, front and back, presenting both graphic and textual information. Reports are delivered to all staff working in the four LTC facilities. The primary evaluation uses a controlled interrupted time series design both adjusted and unadjusted for covariates. The concurrent process evaluation uses observation and self-report to assess uptake of the feedback reports. Following the project phase described in this protocol, a similar intervention will be conducted in home care settings in Alberta. Depending on project findings, if they are judged useful by decision makers participating in this research

  17. Data for improvement and clinical excellence: protocol for an audit with feedback intervention in long-term care.

    Science.gov (United States)

    Sales, Anne E; Schalm, Corinne

    2010-10-13

    There is considerable evidence about the effectiveness of audit coupled with feedback, although few audit with feedback interventions have been conducted in long-term care (LTC) settings to date. In general, the effects have been found to be modest at best, although in settings where there has been little history of audit and feedback, the effects may be greater, at least initially. The primary purpose of the Data for Improvement and Clinical Excellence (DICE) Long-Term Care project is to assess the effects of an audit with feedback intervention delivered monthly over 13 months in four LTC facilities. The research questions we addressed are:1. What effects do feedback reports have on processes and outcomes over time?2. How do different provider groups in LTC and home care respond to feedback reports based on data targeted at improving quality of care? The research team conducting this study comprises researchers and decision makers in continuing care in the province of Alberta, Canada. The intervention consists of monthly feedback reports in nine LTC units in four facilities in Edmonton, Alberta. Data for the feedback reports comes from the Resident Assessment Instrument Minimum Data Set (RAI) version 2.0, a standardized instrument mandated for use in LTC facilities throughout Alberta. Feedback reports consist of one page, front and back, presenting both graphic and textual information. Reports are delivered to all staff working in the four LTC facilities. The primary evaluation uses a controlled interrupted time series design both adjusted and unadjusted for covariates. The concurrent process evaluation uses observation and self-report to assess uptake of the feedback reports. Following the project phase described in this protocol, a similar intervention will be conducted in home care settings in Alberta. Depending on project findings, if they are judged useful by decision makers participating in this research team, we plan dissemination and spread of the feedback

  18. Biofiltration of volatile pollutants: Engineering mechanisms for improved design, long-term operation, prediction, and implementation. 1997 annual progress report

    International Nuclear Information System (INIS)

    Barton, J.W.; Davison, B.H.; Klasson, K.T.

    1997-01-01

    'Biofiltration systems can be used to treat volatile organic compounds (VOCs); however, the systems are poorly understood and are currently operated as black boxes. Common operational problems associated with biofilters include fouling, deactivation, and overgrowth, all of which make biofilters ineffective for continuous, long-term use. The objective of this investigation is to develop generic methods for long-term stable operation, in particular by using selective limitation of supplemental nutrients while maintaining high activity and the ability to regenerate biofilter activity. As part of this effort, the authors will provide a deeper fundamental understanding of the important biological and transport mechanisms in biodestruction of sparingly soluble VOCs and will extend this engineering approach and developed mathematical models to two additional systems of high-priority environmental management (EM) relevance-direct degradation and cometabolic degradation of priority pollutants such as BTEX (benzene, toluene, ethylbenzene, and xylene) and TCE (trichioroethylene), respectively. Preliminary results indicate that the author can control overgrowth of the biofilm while sustaining high degradation rates and develop basic predictive models that elucidate mass transfer and kinetic limitations in this system for alkanes. The alkanes are degraded into CO, and waterwith minimal biomass (due to the methodology proposed). This system will be used to test and model additional supplemental nutrient feeding strategies as well as methods to increase the fundamental driving forces by modification of the system. Models will be extended to non-steady-state, long-term operation. The author will examine the nature of the mixed microbial community in the VOC-degrading biofilm and test for new degradative activities. He will use cosolvents with surfactant properties to enhance hydrocarbon solubility in the biofilm and evaluate their impact on mass transfer and reaction rate in an

  19. Long-term improvements in oral communication skills and quality of peer relations in children with cochlear implants: parental testimony.

    Science.gov (United States)

    Bat-Chava, Y; Martin, D; Imperatore, L

    2014-11-01

    Few research studies have examined longitudinal improvements in oral communication skills and quality of peer relationships of children with implants. Moreover, although the emerging literature suggests that improvement in social functioning follows improvement in oral communication, it is still unknown what factors enhance or impede the relations between these constructs. Based on parent interviews, the current study examined the long-term improvements in speech and oral language skills and relationships with hearing peers in 19 implanted children. Results demonstrate that on average, children continue to improve in oral communication skills and quality of peer relationships even years after implantation, especially those with initial poorer skills. While oral communication ability and quality of peer relationships are strongly associated at each time point, gains in these two variables are associated only for some of the children. Other factors, including self-confidence and peer acceptance, seem to moderate this relationship. Qualitative data are presented to illustrate these relations among variables and to assist in theory building. The results highlight the need for more specific examination of various developmental periods in combination with the progress of oral communication and peer relationships among children with implants. © 2013 John Wiley & Sons Ltd.

  20. Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS.

    Science.gov (United States)

    Nichols, Nicole L; Satriotomo, Irawan; Harrigan, Daniel J; Mitchell, Gordon S

    2015-11-01

    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1(G93A) (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600 μM; 12 μL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms

  1. Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice

    Science.gov (United States)

    Grundy, Trent; Toben, Catherine; Jaehne, Emily J.; Corrigan, Frances; Baune, Bernhard T.

    2014-01-01

    Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3–7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α. PMID:25484856

  2. Long-Term Follow-Up of Patients with Spasmodic Dysphonia and Improved Voice despite Discontinuation of Treatment.

    Science.gov (United States)

    Geneid, Ahmed; Lindestad, Per-Åke; Granqvist, Svante; Möller, Riitta; Södersten, Maria

    2016-01-01

    To evaluate voice function in patients with adductor spasmodic dysphonia (AdSD) who discontinued botulinum toxin (BTX) treatment because they felt that their voice had improved sufficiently. Twenty-eight patients quit treatment in 2004, of whom 20 fulfilled the inclusion criteria for the study, with 3 subsequently excluded because of return of symptoms, leaving 17 patients (11 males, 6 females) included in this follow-up study. A questionnaire concerning current voice function and the Voice Handicap Index were completed. Audio-perceptual voice assessments were done by 3 listeners. The inter- and intrarater reliabilities were r > 0.80. All patients had a subjectively good stable voice, but with differences in their audio-perceptual voice assessment scores. Based on the pre-/posttreatment auditory scores on the overall degree of AdSD, patients were divided into 2 subgroups showing more and less improvement, with 10 and 7 patients, respectively. The subgroup with more improvement had shorter duration from the onset of symptoms until the start of BTX treatment, and included 7 males compared to only 4 males in the subgroup with less improvement. It seems plausible that the symptoms of spasmodic dysphonia may decrease over time. Early intervention and male gender seem to be important factors for long-term reduction of the voice symptoms of AdSD. © 2016 S. Karger AG, Basel.

  3. High-level transfer and long-term expression of the human beta-globin gene in a mouse transplant model.

    Science.gov (United States)

    Raftopoulos, H; Ward, M; Bank, A

    1998-06-30

    Insertion of a normally functioning human beta-globin gene into the hematopoietic stem cells (HSC) of patients with beta-thalassemia may be an effective approach to the therapy of this disorder. Safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models are prerequisites for HSC somatic gene therapy. We have recently shown for the first time that, using a modified beta-globin retroviral vector in a mouse transplant model, long-term, high-level expression of a transferred human beta-globin gene is possible. The human beta-globin gene continues to be detected up to eight months post-transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice. The transferred human beta-globin gene is detected in three of five mice surviving long-term (> 4 months) transplanted with bone marrow cells transduced with high-titer virus. The unrearranged 5.1 kb human beta-globin gene-containing provirus is seen by Southern blotting in two of these mice. More importantly, long-term expression of the transferred gene is seen in two mice at levels of 5% and 20% that of endogenous murine beta-globin. We document stem cell transduction by showing continued high-level expression of the human beta-globin gene in secondarily transplanted recipient mice. These results provide evidence of HSC transduction with a human beta-globin gene in animals and demonstrate that retroviral-mediated unrearranged human beta-globin gene transfer leads to a high level of human beta-globin gene expression in the long term for the first time. A gene therapy strategy may be a feasible therapeutic approach to the beta-thalassemias if consistent human beta-globin gene transfer and expression into HSC can be achieved.

  4. CREB expression in the brains of two closely related parasitic wasp species that differ in long-term memory formation

    NARCIS (Netherlands)

    Van den Berg, M.; Verbaarschot, P.; Hontelez, S.; Vet, L.E.M.; Dicke, M.; Smid, H.M.

    2010-01-01

    The cAMP/PKA signalling pathway and transcription factor cAMP response element-binding protein (CREB) play key roles in long-term memory (LTM) formation. We used two closely related parasitic wasp species, Cotesia glomerata and Cotesia rubecula, which were previously shown to be different in LTM

  5. Computerised clinical decision support systems to improve medication safety in long-term care homes: a systematic review.

    Science.gov (United States)

    Marasinghe, Keshini Madara

    2015-05-12

    Computerised clinical decision support systems (CCDSS) are used to improve the quality of care in various healthcare settings. This systematic review evaluated the impact of CCDSS on improving medication safety in long-term care homes (LTC). Medication safety in older populations is an important health concern as inappropriate medication use can elevate the risk of potentially severe outcomes (ie, adverse drug reactions, ADR). With an increasing ageing population, greater use of LTC by the growing ageing population and increasing number of medication-related health issues in LTC, strategies to improve medication safety are essential. Databases searched included MEDLINE, EMBASE, Scopus and Cochrane Library. Three groups of keywords were combined: those relating to LTC, medication safety and CCDSS. One reviewer undertook screening and quality assessment. Overall findings suggest that CCDSS in LTC improved the quality of prescribing decisions (ie, appropriate medication orders), detected ADR, triggered warning messages (ie, related to central nervous system side effects, drug-associated constipation, renal insufficiency) and reduced injury risk among older adults. CCDSS have received little attention in LTC, as attested by the limited published literature. With an increasing ageing population, greater use of LTC by the ageing population and increased workload for health professionals, merely relying on physicians' judgement on medication safety would not be sufficient. CCDSS to improve medication safety and enhance the quality of prescribing decisions are essential. Analysis of review findings indicates that CCDSS are beneficial, effective and have potential to improve medication safety in LTC; however, the use of CCDSS in LTC is scarce. Careful assessment on the impact of CCDSS on medication safety and further modifications to existing CCDSS are recommended for wider acceptance. Due to scant evidence in the current literature, further research on implementation and

  6. Long-Term Effect of a Leonardite Iron Humate Improving Fe Nutrition As Revealed in Silico, in Vivo, and in Field Experiments.

    Science.gov (United States)

    Cieschi, María T; Caballero-Molada, Marcos; Menéndez, Nieves; Naranjo, Miguel A; Lucena, Juan J

    2017-08-09

    Novel, cheap and ecofriendly fertilizers that solve the usual iron deficiency problem in calcareous soil are needed. The aim of this work is to study the long-term effect of an iron leonardite fertilizer on citrus nutrition taking into account a properly characterization, kinetic response with a ligand competition experiment, efficiency assessment using Saccharomyces cerevisiae strain and finally, in field conditions with citrus as test plants. Its efficiency was compared with the synthetic iron chelate FeEDDHA. Leonardite iron humate (LIH) is mainly humic acid with a high-condensed structure where iron is present as ferrihydrite and Fe 3+ polynuclear compounds stabilized by organic matter. Iron and humic acids form aggregates that decrease the iron release from these kinds of fertilizers. Furthermore, LIH repressed almost 50% of the expression of FET3, FTR1, SIT1, and TIS11 genes in Saccharomyces cerevisiae cells, indicating increasing iron provided in cells and improved iron nutrition in citrus.

  7. Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

    Science.gov (United States)

    Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

    2003-09-01

    The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

  8. Improvement of Renal Function by Long-Term Sustained Eculizumab Treatment in a Patient with Paroxysmal Nocturnal Hemoglobinuria

    Directory of Open Access Journals (Sweden)

    Haruhiko Ninomiya

    2015-01-01

    Full Text Available Chronic kidney disease (CKD is one of the major manifestations of paroxysmal nocturnal hemoglobinuria (PNH. CKD in PNH is induced mainly by intravascular hemolysis of PNH-affected red blood cells (RBC missing the glycosylphosphatidylinositol-anchored proteins with complement-regulatory activities, CD55 and CD59. CKD develops by heme absorption in the proximal tubules resulting in the interstitial deposition of iron in the kidneys. We administered eculizumab to a patient with PNH, who was one of 29 patients enrolled in the AEGIS clinical trial, an open-label study of eculizumab in Japan. The patient was complicated by stage 3 CKD with impaired estimated glomerular filtration rate (eGFR, at grade G3b, and had obvious proteinuria (2-3+, 1-2 g/day. In a two-year extension to the 12-week AEGIS study, eGFR improved significantly, and the eGFR has since been maintained at grade G2 without proteinuria by sustained eculizumab treatment (>6 years. Renal function improved and maintained by long-term sustained eculizumab treatment, presumably by clearance of iron from the kidney as well as inhibition of the production of anaphylatoxin C5a, even in advanced stages of CKD, is one of the benefits of eculizumab treatment in PNH.

  9. SCOPEOUT: sustainability and spread of quality improvement activities in long-term care- a mixed methods approach.

    Science.gov (United States)

    Cranley, Lisa A; Hoben, Matthias; Yeung, Jasper; Estabrooks, Carole A; Norton, Peter G; Wagg, Adrian

    2018-03-12

    Interventions to improve quality of care for residents of long-term care facilities, and to examine the sustainability and spread of such initiatives, remain a top research priority. The purpose of this exploratory study was to assess the extent to which activities initiated in a quality improvement (QI) collaborative study using care aide led teams were sustained or spread following cessation of the initial project and to identify factors that led to its success. This study used an exploratory mixed methods study design and was conducted in seven residential long-term care facilities in two Canadian provinces. Sustainability and spread of QI activities were assessed by a questionnaire over five time points for 18 months following the collaborative study with staff from both intervention with non-intervention units. Semi-structured interviews were conducted with care managers at six and 12 months. QI team success in applying the QI model was ranked as high, medium, or low using criteria developed by the research team. Descriptive statistics, bivariate analyses, and General Estimating Equations were used to analyze the data. Interview data were analyzed using thematic analysis. In total, 683 surveys were received over the five time periods from 476 unique individuals on a facility unit. Seven managers were interviewed. A total of 533 surveys were analyzed. While both intervention and non-intervention units experienced a decline over time in all outcome measures, this decline was significantly less pronounced on intervention units. Facilities with medium and high success ranking had significantly higher scores in all four outcomes than facilities with a low success ranking. Care aides reported significantly less involvement of others in QI activities, less empowerment and less satisfaction with the quality of their work life than regulated care providers. Manager interviews provided evidence of sustainability of QI activities on the intervention units in four of

  10. Long-Term Improvements in Knowledge and Psychosocial Factors of a Teen Pregnancy Prevention Intervention Implemented in Group Homes.

    Science.gov (United States)

    Green, Jennifer; Oman, Roy F; Lu, Minggen; Clements-Nolle, Kristen D

    2017-06-01

    Youth in out-of-home care have higher rates of sexual risk behaviors and pregnancy than youth nationally. This study aimed to determine if Power Through Choices (PTC), a teen pregnancy prevention program developed for youth in out-of-home care, significantly improves knowledge and psychosocial outcomes regarding HIV and sexually transmitted infections (STIs), sexual activity and contraception methods, long term. A cluster randomized controlled trial was conducted with 1,036 ethnically diverse youths (aged 13-18 years) recruited from 44 residential group homes in three states. Intervention participants received the 10-session PTC intervention; control participants received usual care. Participants were administered self-report surveys at baseline, after intervention, 6 and 12 months after the intervention. Survey items assessed knowledge, attitudes, self-efficacy, and behavioral intentions regarding HIV and STIs, sexual activity and contraception methods. Random intercept logistic regression analyses were used to assess differences between the intervention and control groups. Compared with youth in the control group, youth in the PTC intervention demonstrated significant improvements in knowledge about anatomy and fertility (adjusted odds ratio [AOR] = 1.07, 95% confidence interval [CI] = 1.03-1.11), HIV and STIs (AOR = 1.03, 95% CI = 1.002-1.07), and methods of protection (AOR = 1.06, 95% CI = 1.03-1.09), as well as self-efficacy regarding self-efficacy to communicate with a partner (AOR = 1.14, 95% CI = 1.04-1.26), plan for protected sex and avoid unprotected sex (AOR = 1.16, 95% CI = 1.04-1.28), and where to get methods of birth control (AOR = 1.13, 95% CI = 1.01-1.26) 12 months after the intervention. Findings suggest that the PTC intervention can have positive long-term knowledge and psychosocial effects regarding contraception methods on youth in out-of-home care. Copyright © 2017 Society for Adolescent Health and Medicine. Published by

  11. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    International Nuclear Information System (INIS)

    Boda-Heggemann, J.; Schneider, V.; Weiss, C.

    2013-01-01

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  12. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, J.; Schneider, V. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Radiation Oncology; Weiss, C. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Biomathematics and Medical Statistics] [and others

    2013-05-15

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  13. Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2014-06-01

    Full Text Available Haya Ascher-Svanum,1 Diego Novick,2,3 Josep Maria Haro,4 Jordan Bertsch,4 David McDonnell,1 Holland Detke11Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, Surrey, UK; 3Departament de Psiquiatria, Universitat Autonoma de Barcelona, Spain; 4Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red en el Área de Salud Mental, Universitat de Barcelona, Barcelona, SpainBackground: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI, and whether observed changes differ from those seen with oral olanzapine.Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264 with daily oral olanzapine (10 mg/day; n=260. Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score from 64.0–70.8 (P<0.001. Patients on oral ­olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001. At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05. The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001. Results did not significantly differ between

  14. Improved work ability and return to work following vocational multidisciplinary rehabilitation of subjects on long-term sick leave

    OpenAIRE

    Braathen, Tore; Veiersted, Kaj Bo; Heggenes, Jan

    2007-01-01

    Objective: To evaluate a vocational multidisciplinary rehabilitation programme for patients on long-term sick leave with respect to their work ability and return to work. Methods: A multidisciplinary rehabilitation programme was administered to an intervention group of 183 patients on long-term sick leave (mean 12.2 months). Effects of the treatment were compared with a control group (n = 96) recruited from the national sickness insurance record of patients on sick leave of 6??2 month...

  15. Minimal doses of a sequence-optimized transgene mediate high-level and long-term EPO expression in vivo: challenging CpG-free gene design.

    Science.gov (United States)

    Kosovac, D; Wild, J; Ludwig, C; Meissner, S; Bauer, A P; Wagner, R

    2011-02-01

    Advanced gene delivery techniques can be combined with rational gene design to further improve the efficiency of plasmid DNA (pDNA)-mediated transgene expression in vivo. Herein, we analyzed the influence of intragenic sequence modifications on transgene expression in vitro and in vivo using murine erythropoietin (mEPO) as a transgene model. A single electro-gene transfer of an RNA- and codon-optimized mEPOopt gene into skeletal muscle resulted in a 3- to 4-fold increase of mEPO production sustained for >1 year and triggered a significant increase in hematocrit and hemoglobin without causing adverse effects. mEPO expression and hematologic levels were significantly lower when using comparable amounts of the wild type (mEPOwt) gene and only marginal effects were induced by mEPOΔCpG lacking intragenic CpG dinucleotides, even at high pDNA amounts. Corresponding with these observations, in vitro analysis of transfected cells revealed a 2- to 3-fold increased (mEPOopt) and 50% decreased (mEPOΔCpG) erythropoietin expression compared with mEPOwt, respectively. RNA analyses demonstrated that the specific design of the transgene sequence influenced expression levels by modulating transcriptional activity and nuclear plus cytoplasmic RNA amounts rather than translation. In sum, whereas CpG depletion negatively interferes with efficient expression in postmitotic tissues, mEPOopt doses <0.5 μg were sufficient to trigger optimal long-term hematologic effects encouraging the use of sequence-optimized transgenes to further reduce effective pDNA amounts.

  16. Quality of life long-term after body contouring surgery following bariatric surgery: sustained improvement after 7 years.

    Science.gov (United States)

    van der Beek, Eva S J; Geenen, Rinie; de Heer, Francine A G; van der Molen, Aebele B Mink; van Ramshorst, Bert

    2012-11-01

    Bariatric surgery for morbid obesity results in massive weight loss and improvement of health and quality of life. A downside of the major weight loss is the excess of overstretched skin, which may influence the patient's quality of life by causing functional and aesthetic problems. The purpose of the current study was to evaluate the patient's quality of life long-term after body contouring following bariatric surgery. Quality of life was measured with the Obesity Psychosocial State Questionnaire in 33 post-bariatric surgery patients 7.2 years (range, 3.2 to 13.3 years) after body contouring surgery. Data were compared with previous assessments 4.1 years (range, 0.7 to 9.2 years) after body contouring surgery of the quality of life at that time and before body contouring surgery. Compared with appraisals of quality of life before body contouring surgery, a significant, mostly moderate to large, sustained improvement of quality of life was observed in post-bariatric surgery patients 7.2 years after body contouring surgery in six of the seven psychosocial domains. A small deterioration occurred between 4.1- and 7.2-year follow-up on two of the seven domains except for the domain efficacy toward eating, which showed a significant improvement. At 7-year follow-up, 18 patients (55 percent) were satisfied with the result of body contouring surgery. This study indicates a sustained quality-of-life improvement in post-bariatric surgery patients after body contouring surgery. This suggests the importance of including reconstructive surgery as a component in the multidisciplinary approach in the surgical treatment of morbid obesity. Therapeutic, IV.

  17. Curcuma comosa improves learning and memory function on ovariectomized rats in a long-term Morris water maze test

    Science.gov (United States)

    Su, Jian; Sripanidkulchai, Kittisak; Wyss, J. Michael; Sripanidkulchai, Bungorn

    2010-01-01

    Aim of the study Curcuma comosa extract and some purified compounds from this plant have been reported to have estrogenic-like effects, and estrogen improves learning in some animals and potentially in postmenopausal women; therefore, this study tested the hypothesis that Curcuma comosa and estrogen have similar beneficial effects on spatial learning and memory. Materials and methods Curcuma comosa hexane extract, containing 0.165 mg of (4E,6E)-1,7-diphenylhepta-4,6-dien-3-one per mg of the crude extract, was orally administered to ovariectomized Wistar rats at the doses of 250 or 500 mg/kg body weight. 17β-estradiol (10 μg/kg body weight, subcutaneously) was used as a positive control. Thirty days after the initiation of treatment, animals were tested in a Morris water maze for spatial learning and memory. They were re-tested every 30 days and a final probe trial was run on day 119. Results Compared to control rats, OVX rats displayed significant memory impairment for locating the platform in the water maze from day 67 after the surgery, onward. In contrast, OVX rats treated with either Curcuma comosa or estrogen were significantly protected from this decline in cognitive function. Further, the protection of cognitive effects by Curcuma comosa was larger at higher dose. Conclusions These results suggest that long-term treatment with Curcuma comosa has beneficial effects on learning and memory function in rats. PMID:20420894

  18. Study on improvement in reliability of inventory assessment in vitrified waste for long-term safety of geological disposal

    International Nuclear Information System (INIS)

    Ishikawa, Masumi; Kaneko, Satoru; Kitayama, Kazumi; Ishiguro, Katsuhiko; Ueda, Hiroyoshi; Wakasugi, Keiichiro; Shinohara, Nobuo; Okumura, Keisuke; Chino, Masamichi; Moriya, Noriyasu

    2009-01-01

    Since quality control issues for vitrified waste are defined mainly with the focus on the transport and interim storage of the waste rather than the long-term safety of geological disposal, they do not cover inventories of long-lived nuclides that are of most interest in the safety assessment of geological disposal. Therefore, we suggest a flow chart for the assessment of inventories of long-lived nuclides in the vitrified waste focusing on the measured values. This includes an indirect assessment with indicative nuclides that have been already measured in the returned vitrified wastes from abroad. In order to apply this flow chart for commercial operation, its applicability should be examined for cases with a variation in burn-up history and with an uncertainty associated with carry-over fraction at reprocessing. We started an R and D program to examine the applicability as well as to improve the reliability of the nuclide generation/decay code and the nuclear data library using liquid waste from spent fuel with a clear irradiation history. To solve the issue of quality control for vitrified waste, a comprehensive study is needed in aspects not only of geological disposal field but also of operation of a nuclear power plant, reprocessing of spent fuel and vitrification of liquid waste. This study is a pioneering study conducted to integrate them. (author)

  19. Long-term survival differences in gastric cancer after D2 lymphadenectomy and an improved assessment of resectability

    Directory of Open Access Journals (Sweden)

    Gabriel Dimofte

    2017-05-01

    Full Text Available Objective. The purpose of this work is to compare the long-term survival between a control group with mostly D1 lymphadenectomy and a study group with mostly D2 lymphadenectomy. Materials and Methods. We analyzed consecutive cases operated by a single surgeon performing mostly D2 lymphadenectomy and a control group of consecutive gastric cancer patients operated by a group of surgeons, performing mostly D1 lymphadenectomy, in a period when D2 lymphadenectomy was not the standard and was introduced as a new technique in our center. Results. We found 30,56% D2 lymphadenectomy in the control groups and 85,1% in the study group. At a five years interval from surgery the control group had no survivors, while the study group had 8 (20% survivors. Conclusions. The spleen and pancreas preserving D2 lymphadenectomy done by experienced surgeons, according to the current guidelines in order to select operable patients improves the overall survival of such gastric cancer patients.

  20. Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum.

    Science.gov (United States)

    Rancillac, Armelle; Crépel, Francis

    2004-02-01

    Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long-term changes in synaptic efficacy. In the present study, we show that long-term potentiation (LTP) and long-term depression (LTD) were induced at these synapses by a low frequency stimulation protocol (2 Hz for 60 s) and that pairing this low frequency stimulation protocol with postsynaptic depolarization induced a marked shift of synaptic plasticity in favour of LTP. This LTP was cAMP independent, but required nitric oxide (NO) production from pre- and/or postsynaptic elements, depending on the stimulation or pairing protocol used, respectively. In contrast, LTD was not dependent on NO production but it required activation of postsynaptic group II and possibly of group I metabotropic glutamate receptors. Finally, stimulation of PFs at 8 Hz for 15 s also induced LTP at PF-SC synapses. But in this case, LTP was cAMP dependent, as was also observed at PF-PC synapses for presynaptic LTP induced in the same conditions. Thus, long-term changes in synaptic efficacy can be accomplished by PF-SCs synapses as well as by PF-PC synapses, suggesting that both types of plasticity might co-operate during cerebellar motor learning.

  1. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

    International Nuclear Information System (INIS)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-01-01

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca 2+ permeability, we investigated whether Ca 2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca 2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  2. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate.

    Science.gov (United States)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-10-15

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca2+ permeability, we investigated whether Ca2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  3. Changes in gene expression caused by insect venom immunotherapy responsible for the long-term protection of insect venom-allergic patients

    NARCIS (Netherlands)

    Niedoszytko, Marek; Bruinenberg, Marcel; de Monchy, Jan; Weersma, Rinse K.; Wijmenga, Cisca; Jassem, Ewa; Oude Elberink, Joanne N. G.

    Background: Insect venom immunotherapy (VIT) is the only causative treatment of insect venom allergy (IVA). The immunological mechanism(s) responsible for long-term protection achieved by VIT are largely unknown. A better understanding is relevant for improving the diagnosis, prediction of

  4. Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants.

    Science.gov (United States)

    De Faveri, Sara; Maggiolini, Emma; Miele, Ermanno; De Angelis, Francesco; Cesca, Fabrizia; Benfenati, Fabio; Fadiga, Luciano

    2014-01-01

    The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes - over time - compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

  5. Bio-inspired hybrid microelectrodes. A hybrid solution to improve long-term performance of chronic intracortical implants.

    Directory of Open Access Journals (Sweden)

    Sara eDe Faveri

    2014-04-01

    Full Text Available The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes - over time - compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

  6. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study.

    Science.gov (United States)

    Buchman, A L; Sohel, M; Brown, M; Jenden, D J; Ahn, C; Roch, M; Brawley, T L

    2001-01-01

    Previous investigations have demonstrated that choline deficiency, manifested in low plasma-free choline concentration and hepatic injury, may develop in patients who require long-term total parenteral nutrition (TPN). Preliminary studies have suggested lecithin or choline supplementation might lead to improved visual memory in the elderly and reverse abnormal neuropsychological development in children. We sought to determine if choline-supplemented TPN would lead to improvement in neuropsychological test scores in a group of adult, choline-deficient outpatients receiving TPN. Eleven subjects (8 males, 3 females) who received nightly TPN for more than 80% of their nutritional needs for at least 12 weeks before entry in the study were enrolled. Exclusion criteria included active drug abuse, mental retardation, cerebral vascular accident, head trauma, hemodialysis or peritoneal dialysis, (prothrombin time [PT] >2x control), or acquired immune deficiency syndrome (AIDS). Patients were randomly assigned to receive their usual TPN regimen (n = 6, aged 34.0 +/- 12.6 years) over a 12-hour nightly infusion or their usual TPN regimen plus choline chloride (2 g) (n = 5, aged 37.3 +/- 7.3 years). The following neuropsychological tests were administered at baseline and after 24 weeks of choline supplementation (or placebo): Weschler Adult Intelligence Scale-Revised (WAIS-R, intellectual functioning), Weschler Memory Scale-Revised (WMS-R, two subtests, verbal and visual memory), Rey-Osterrieth Complex Figure Test (visuospatial functioning and perceptual organization), Controlled Oral Word Association Test (verbal fluency), Grooved Pegboard (manual dexterity and motor speed), California Verbal Learning Test (CVLT, rote verbal learning ability), and Trail Making Parts A & B (visual scanning, psychomotor speed and set shifting). Scores were reported in terms of standard scores including z scores and percentile ranks. Mean absolute changes in raw scores were compared between groups

  7. Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver.

    Science.gov (United States)

    Vuica, Ana; Ferhatović Hamzić, Lejla; Vukojević, Katarina; Jerić, Milka; Puljak, Livia; Grković, Ivica; Filipović, Natalija

    2015-12-01

    Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation

    OpenAIRE

    Dale, Erica A.; Fields, Daryl P.; Devinney, Michael J.; Mitchell, Gordon S.

    2016-01-01

    Phrenic long-term facilitation (pLTF) is a form of hypoxia-induced spinal respiratory motor plasticity that requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB). Since the cellular location of relevant TrkB receptors is not known, we utilized intrapleural siRNA injections to selectively knock down TrkB receptor protein within phrenic motor neurons. TrkB receptors within phrenic motor neurons are n...

  9. A multicomponent exercise program improves physical function in long-term nursing home residents: A randomized controlled trial.

    Science.gov (United States)

    Arrieta, Haritz; Rezola-Pardo, Chloe; Zarrazquin, Idoia; Echeverria, Iñaki; Yanguas, Jose Javier; Iturburu, Miren; Gil, Susana Maria; Rodriguez-Larrad, Ana; Irazusta, Jon

    2018-03-01

    To investigate the impact of a multicomponent exercise program on anthropometry, physical function, and physical activity on older adults living in long-term nursing homes (LTNH), we conducted a randomized controlled trial involving 112 participants aged 84.9 ± 6.9 years. Participants were randomly assigned to an intervention (IG) or control group (CG). The IG participated in a 3-month multicomponent exercise intervention focused on strength, balance, stretching exercises, and walking recommendations. Subjects in the CG participated in routine activities. Analyses of outcome parameters were performed in the entire sample and in two subgroups, classified according to participants' physical function score at baseline. The group-by-time interaction, favoring the IG, was significant for the entire sample and for the participants in the low physical function subgroup for the following parameters: waist circumference, 30-s chair-stand, arm-curl, 8-ft timed up-and-go, SPPB score, gait speed, and Berg scale (p < .05). In participants with higher physical function at baseline, significant group-by-time interaction was observed in the SPPB score and Berg scale (p < .05). When differences were analyzed within groups, the IG maintained or improved in all assessed parameters, while participants in the CG showed a marked decline. Our study showed that a multicomponent exercise program is effective for older people living in LTNH. This is especially relevant in those with lower physical function scores. The lower efficacy of the program in participants with better function might be due to the insufficient exercise demands of our intervention for more fit residents. Future studies should analyze the effects of programs with higher intensities in older people with intermediate to high physical function. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Incorporating technology buying behaviour into UK-based long term domestic stock energy models to provide improved policy analysis

    International Nuclear Information System (INIS)

    Lee, Timothy; Yao, Runming

    2013-01-01

    The UK has a target for an 80% reduction in CO 2 emissions by 2050 from a 1990 base. Domestic energy use accounts for around 30% of total emissions. This paper presents a comprehensive review of existing models and modelling techniques and indicates how they might be improved by considering individual buying behaviour. Macro (top-down) and micro (bottom-up) models have been reviewed and analysed. It is found that bottom-up models can project technology diffusion due to their higher resolution. The weakness of existing bottom-up models at capturing individual green technology buying behaviour has been identified. Consequently, Markov chains, neural networks and agent-based modelling are proposed as possible methods to incorporate buying behaviour within a domestic energy forecast model. Among the three methods, agent-based models are found to be the most promising, although a successful agent approach requires large amounts of input data. A prototype agent-based model has been developed and tested, which demonstrates the feasibility of an agent approach. This model shows that an agent-based approach is promising as a means to predict the effectiveness of various policy measures. - Highlights: ► Long term energy models are reviewed with a focus on UK domestic stock models. ► Existing models are found weak in modelling green technology buying behaviour. ► Agent models, Markov chains and neural networks are considered as solutions. ► Agent-based modelling (ABM) is found to be the most promising approach. ► A prototype ABM is developed and testing indicates a lot of potential.

  11. Transplantation of mouse HSCs genetically modified to express a CD4-restricted TCR results in long-term immunity that destroys tumors and initiates spontaneous autoimmunity.

    Science.gov (United States)

    Ha, Sung P; Klemen, Nicholas D; Kinnebrew, Garrett H; Brandmaier, Andrew G; Marsh, Jon; Hangoc, Giao; Palmer, Douglas C; Restifo, Nicholas P; Cornetta, Kenneth; Broxmeyer, Hal E; Touloukian, Christopher E

    2010-12-01

    The development of effective cancer immunotherapies has been consistently hampered by several factors, including an inability to instigate long-term effective functional antitumor immunity. This is particularly true for immunotherapies that focus on the adoptive transfer of activated or genetically modified mature CD8+ T cells. In this study, we sought to alter and enhance long-term host immunity by genetically modifying, then transplanting, mouse HSCs. We first cloned a previously identified tumor-reactive HLA-DR4-restricted CD4+ TCR specific for the melanocyte differentiation antigen tyrosinase-related protein 1 (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR-transgenic mouse expressing the genes encoding this TCR. Using these tools, we demonstrated that both mouse and human HSCs established durable, high-efficiency TCR gene transfer following long-term transplantation into lethally irradiated mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs developed spontaneous autoimmune vitiligo that was associated with the presence of a Th1-polarized memory effector CD4+ T cell population that expressed the Tyrp1-specific TCR. Most importantly, large numbers of CD4+ T cells expressing the Tyrp1-specific TCR were detected in secondary HLA-DR4-transgenic transplant recipients, and these mice were able to destroy subcutaneously administered melanoma cells without the aid of vaccination, immune modulation, or cytokine administration. These results demonstrate the creation of what we believe to be a novel translational model of durable lentiviral gene transfer that results in long-term effective immunity.

  12. Mindfulness-based program for children with autism spectrum disorder and their parents: Direct and long-term improvements

    NARCIS (Netherlands)

    Ridderinkhof, A.; de Bruin, E.I.; Blom, 'R.; Bögels, S.M.

    A combined mindfulness-based program for children and their parents (MYmind) was beneficial for adolescents with autism spectrum disorder (ASD). In this study, we investigated whether this program is also beneficial for younger children with ASD, whether effects last on the long-term, and whether it

  13. Development of a Curriculum for Long-Term Care Nurses to Improve Recognition of Depression in Dementia

    Science.gov (United States)

    Williams, Christine L.; Molinari, Victor; Bond, Jennifer; Smith, Michael; Hyer, Kathryn; Malphurs, Julie

    2006-01-01

    There is increasing recognition of the severe consequences of depression in long-term care residents with dementia. Most health care providers are unprepared to recognize and to manage the complexity of depression in dementia. Targeted educational initiatives in nursing homes are needed to address this growing problem. This paper describes the…

  14. IFNy+ and IFNy- Treg subsets with stable and unstable Foxp3 expression in kidney transplant recipients with good long-term graft function.

    Science.gov (United States)

    Trojan, Karina; Unterrainer, Christian; Aly, Mostafa; Zhu, Li; Weimer, Rolf; Bulut, Nuray; Morath, Christian; Opelz, Gerhard; Daniel, Volker

    2016-10-29

    Treg are a heterogenous cell population. In the present study we attempted to identify Treg subsets that might contribute to stable and good long-term graft function. Lymphocyte and Treg subsets were studied in 136 kidney transplant recipients with good long-term graft function and in 52 healthy control individuals using eight-color-fluorescence flow cytometry. Foxp3 TSDR methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations using high resolution melt analysis. Compared with healthy controls, patients showed strong associations of IFNy secreting Helios+ and Helios- Treg with Treg that co-expressed perforin and/or CTLA4 (CD152; pterm graft function possess IFNy+ and IFNy- Treg with stable and unstable Foxp3 expression in the blood. They co-express CD28, HLADR, CTLA4, CXCR3, Lselectin, TGFβ, perforin and FasL and might contribute to the establishment and maintenance of good long-term graft function. Copyright © 2016. Published by Elsevier B.V.

  15. Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice.

    Science.gov (United States)

    Himelstein, A; Ward, M; Podda, S; de la Flor Weiss, E; Costantini, F; Bank, A

    1993-03-01

    When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.

  16. Cholangiocarcinomas associated with long-term inflammation express the activation-induced cytidine deaminase and germinal center-associated nuclear protein involved in immunoglobulin V-region diversification.

    Science.gov (United States)

    Chan-On, Waraporn; Kuwahara, Kazuhiko; Kobayashi, Naoya; Ohta, Kazutaka; Shimasaki, Tatsuya; Sripa, Banchob; Leelayuwat, Chanvit; Sakaguchi, Nobuo

    2009-08-01

    Cholangiocarcinoma (CCA) represents a model of tumor development after long-term inflammation which causes DNA damage or impairs DNA repair mechanism. AID and GANP, both appearing in antigen-driven B cells, are involved in affinity maturation of the immunoglobulin V-region with increased somatic mutation. A normal cholangiocyte line showed the induction of AID transcripts after stimulation with TNF-alpha, whereas ganp transcripts appeared constitutively in this cell line. Next, we examined the expression of AID and GANP in clinical CCA specimens to obtain information whether their expression levels are associated with the malignant grade of CCA. AID expression was similarly detected in the clinical cases of both well-differentiated and poorly-differentiated CCAs. On the contrary, GANP expression was detected in CCA cells at a higher level in the nucleus of poorly-differentiated CCAs with shorter survivals than in that of well-differentiated CCAs. The high and low cases of nuclear GANP expression showed no change in the frequency of the TP53 mutations, however, further investigation by in vitro experiment demonstrated that the high GANP expression caused the increased number of gammaH2AX foci after DNA damage by ionizing-irradiation. These results suggest that GANP is involved in regulation of DNA repair mechanism and the abnormal over-expression of GANP together with AID might be associated with rigorous DNA damage, potentially causing the malignant development of CCAs during long-term inflammation.

  17. Heterogenic expression of stem cell markers in patient-derived glioblastoma spheroid cultures exposed to long-term hypoxia

    DEFF Research Database (Denmark)

    Rosenberg, Tine; Aaberg-Jessen, Charlotte; Petterson, Stine Asferg

    2018-01-01

    AIM: To investigate the time profile of hypoxia and stem cell markers in glioblastoma spheroids of known molecular subtype. MATERIALS & METHODS: Patient-derived glioblastoma spheroids were cultured up to 7 days in either 2% or 21% oxygen. Levels of proliferation (Ki-67), hypoxia (HIF-1α, CA9...... and VEGF) and stem cell markers (CD133, nestin and musashi-1) were investigated by immunohistochemistry. RESULTS: Hypoxia markers as well as CD133 and partially nestin increased in long-term hypoxia. The proliferation rate and spheroid size were highest in normoxia. CONCLUSION: We found differences...... in hypoxia and stem cell marker profiles between the patient-derived glioblastoma cultures. This heterogeneity should be taken into consideration in development of future therapeutic strategies....

  18. Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation.

    Science.gov (United States)

    Dale, Erica A; Fields, Daryl P; Devinney, Michael J; Mitchell, Gordon S

    2017-01-01

    Phrenic long-term facilitation (pLTF) is a form of hypoxia-induced spinal respiratory motor plasticity that requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB). Since the cellular location of relevant TrkB receptors is not known, we utilized intrapleural siRNA injections to selectively knock down TrkB receptor protein within phrenic motor neurons. TrkB receptors within phrenic motor neurons are necessary for BDNF-dependent acute intermittent hypoxia-induced pLTF, demonstrating that phrenic motor neurons are a critical site of respiratory motor plasticity. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Regional improvement of global reanalyses by means of a new long-term Mediterranean hindcasted precipitation dataset: a first study over the Iberian Peninsula

    Directory of Open Access Journals (Sweden)

    M. G. Sotillo

    2006-01-01

    Full Text Available Generation of a Mediterranean long-term (1958-2001 homogeneous high resolution environmental database constituted the main objective whitin the HIPOCAS Project. The high number of parameters included in this database allows a complete characterization of Mediterranean storms. In this paper, the HIPOCAS precipitation reliability over the Iberian Peninsula and the Balearic Islands is evaluated against long-term in-situ observations from Iberia. In order to provide a more complete study, comparisons of the HIPOCAS field with NCEP/NCAR and ERA global reanalysis show the important improvement in the characterisation of the observed precipitation introduced by the HIPOCAS hindcast.

  20. Sustained long-term improvement with clozapine in schizophrenia Clozapina na esquizofrenia grave: melhora duradoura e sustentada

    Directory of Open Access Journals (Sweden)

    RICARDO DE OLIVEIRA-SOUZA

    1999-03-01

    Full Text Available The present paper reports the long-term use of clozapine in a prospective sample of 46 chronic schizophrenics. In six months, 21 subjects had been excluded for a number of reasons. In four of them the reasons for exclusion were related to lack of response or adverse effects. The median daily clozapine dose was 400 mg in the remaining 25 patients. As a whole, there were remarkable improvements in core dimensions of psychopathology, global cognitive status, and level of functioning. We confirmed that clozapine is effective in a subgroup of schizophrenics with the severest forms of the disease. If tolerated after the first few months it leads to progressive gains in several domains of behavior. Clozapine should be tried in every patient with schizophrenia in whom positive symptoms, disorganization, or bizarre behavior are a matter of incapacitation despite efforts to keep them under control with other drugs.O presente estudo, prospectivo, relata o uso de longo-prazo da clozapina em 46 esquizofrênicos graves, com mais de cinco anos de doença. Com seis meses de uso da droga, 21 indivíduos haviam sido excluídos por diversas razões. Em quatro, a exclusão se deveu a efeitos adversos ou ausência de resposta. A dose mediana de clozapina foi de 400 mg nos demais 25 pacientes. No todo, observamos melhora em dimensões de psicopatologia, estado cognitivo global, e nível funcional. Concluímos que a clozapina é eficaz em um subgrupo de esquizofrênicos com formas graves da doença. Se tolerada depois dos primeiros meses, produz benefícios progressivos em diversos domínios do comportamento. Clozapina deve ser tentada em todo paciente com esquizofrenia incapacitado por sintomas positivos, desorganização, e/ou comportamentos bizarros, que persistem a despeito de esforços para mantê-los sob controle com outras drogas.

  1. Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue.

    Science.gov (United States)

    Bozkaya, F; Atli, M O; Guzeloglu, A; Kayis, S A; Yildirim, M E; Kurar, E; Yilmaz, R; Aydilek, N

    2017-08-01

    The aim was to investigate the effects of long-term heat stress and dietary restriction on the expression of certain genes involving in steroidogenic pathway and small heat-shock proteins (sHSPs) in rat testis. Sprague Dawley rats (n = 24) were equally divided into four groups. Group I and II were kept at an ambient temperature of 22°C, while Groups III and IV were reared at 38°C for 9 weeks. Feed was freely available for Group I and Group III, while Group II and Group IV were fed 60% of the diet consumed by their ad libitum counterparts. At the end of 9 weeks, testicles were collected under euthanasia. Total RNA was isolated from testis tissue samples. Expression profiles of the genes encoding androgen-binding protein, follicle-stimulating hormone receptor, androgen receptor, luteinising hormone receptor, steroidogenic acute regulatory protein (StAR), cyclooxygenase-2 and sHSP genes were assessed at mRNA levels using qPCR. Long-term heat stress decreased the expression of StAR and HspB10 genes while dietary restriction upregulated StAR gene expression. The results suggested that long-term heat stress negatively affected the expression of StAR and HspB10 genes and the dietary restriction was able to reverse negative effect of heat stress on the expression of StAR gene in rat testis. © 2016 Blackwell Verlag GmbH.

  2. PEBS: an international challenge for improve understanding of the natural barriers to isolate long-term radioactive waste

    International Nuclear Information System (INIS)

    Gaus, I.

    2015-01-01

    The radioactive materials have a wide range of applications ranging from nuclear reactors to the use of isotopes in industries, medicine or research centres. These technologies generate waste whose disposal systems are becoming more sophisticated, to the point of using artificial barriers able to isolate them from contact with other materials, precipitation, surface water and groundwater subsurface. In this context, the European project long term Performance of the engineered Barrier Systems (PeBS), funded by the seventh framework (Fp7) Euratom and has counted with the participation of ENRESA, reviewed the evolution of the performance of sealing and barrier systems of artificial barriers in relevant time scales through the development of a comprehensive method that includes experiments, models, and a consideration of the potential impacts of long-term security functions. (Author)

  3. Prestimulation with Recombinant Human Thyrotropin (rhTSH) Improves the Long-Term Outcome of Radioiodine Therapy for Multinodular Nontoxic Goiter

    DEFF Research Database (Denmark)

    Fast, Søren; Nielsen, Viveque Egsgaard; Grupe, Peter

    2012-01-01

    goiter volume reduction with rhTSH-augmented (131)I therapy improves the long-term reduction in goiter-related symptoms and reduces the need for additional therapy compared with plain (131)I therapy. Overall patient satisfaction is benefited, despite a higher rate of permanent hypothyroidism....

  4. Assessment of the effectiveness of biofeedback in children with dyssynergic defecation and recalcitrant constipation/encopresis: does home biofeedback improve long-term outcomes.

    Science.gov (United States)

    Croffie, Joseph M; Ammar, M Samer; Pfefferkorn, Marian D; Horn, Debra; Klipsch, Ann; Fitzgerald, Joseph F; Gupta, Sandeep K; Molleston, Jean P; Corkins, Mark R

    2005-01-01

    The purpose of this study was to determine whether biofeedback benefits children with dyssynergic defecation and constipation/encopresis, and whether home biofeedback improves long-term outcomes. Thirty-six patients with chronic constipation who had failed at least 6 months of conventional treatment and demonstrated dyssynergic defecation at anorectal manometry were randomized to biofeedback in the laboratory alone (group 1, n=24) or in the laboratory and at home (group 2, n=12) and followed up at 2, 4, and a mean of 44 months. Thirty patients were available for long-term follow-up. Bowel movements increased in all from a mean of 1.4/week to 5.1, 5.8, and 5.1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Soiling decreased in all from a mean of 5.5/week to 0.6, 0.1, and 1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Laxative use decreased from a mean of 4.1 days/week to 0.6, 0.3, and 0.7 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Twenty-seven of 30 parents ranked their satisfaction a mean of 2.2 (range 1-excellent to 3-good). There were no significant differences in outcomes between the laboratory alone group and the laboratory plus home group. Biofeedback is beneficial for some children with chronic constipation and dyssynergic defecation. Supplemental home biofeedback does not improve long-term outcomes.

  5. An Evidence-Based Cue-Selection Guide and Logic Model to Improve Pressure Ulcer Prevention in Long Term Care

    Science.gov (United States)

    Yap, Tracey L.; Kennerly, Susan M.; Bergstrom, Nancy; Hudak, Sandra L.; Horn, Susan D.

    2015-01-01

    Pressure ulcers (PrUs) have consistently resisted prevention efforts in long term care (LTC) facilities nationwide. Recent research has described cueing innovations that – when selected according to the assumptions and resources of particular facilities – support best practices of PrU prevention. This paper synthesizes that research into a unified, dynamic logic model to facilitate effective staff implementation of a PrU prevention program. PMID:26066791

  6. Expression of Gast, Cckbr, Reg1α genes in rat duodenal epithelial cells upon long-term gastric hypoacidity and after a multiprobiotic administration

    Directory of Open Access Journals (Sweden)

    Dranitsina A. S.

    2014-11-01

    Full Text Available Aim. Determination of the Cckbr, Gast and Reg1α genes expression in rat duodenal epithelial cells upon long- term hypoacidity and with the administration of the multiprobiotic Symbiter. Methods. The experiments were carried out on white non-strain male rats. The hypoacidic state was induced through intraperitoneal injection of omeprazole for 28 days. The level of genes expression was determined by semi-quantitative analysis with RT-PCR Results. The elevation of mRNA levels of the Cckbr and Gast genes in rat duodenal villus and crypt epitheliocytes, the increased expression of the Reg1A gene in crypt epithelial cells were shown as well as the appearance of the Reg1a gene expression in villus epitheliocytes upon hypoacidic conditions were shown. The content of mRNAs of the above mentioned genes decreased or remained at the control level upon the treatment of hypoacidic rats with the multiprobiotic Symbiter. Conclusions. Long-term gastric hypoacidity is accompanied by the changes in expression of the Cckbr, Gast and Reg1a genes in rat duodenum, whereas upon administration of the multiprobiotic Symbiter the pattern of studied gene expression did not changed in the most cases.

  7. Effectiveness of psychological interventions to improve quality of life in people with long-term conditions: rapid systematic review of randomised controlled trials.

    Science.gov (United States)

    Anderson, Niall; Ozakinci, Gozde

    2018-03-27

    Long-term conditions may negatively impact multiple aspects of quality of life including physical functioning and mental wellbeing. The rapid systematic review aimed to examine the effectiveness of psychological interventions to improve quality of life in people with long-term conditions to inform future healthcare provision and research. EBSCOhost and OVID were used to search four databases (PsychInfo, PBSC, Medline and Embase). Relevant papers were systematically extracted by one researcher using the predefined inclusion/exclusion criteria based on titles, abstracts, and full texts. Randomized controlled trial psychological interventions conducted between 2006 and February 2016 to directly target and assess people with long-term conditions in order to improve quality of life were included. Interventions without long-term condition populations, psychological intervention and/or patient-assessed quality of life were excluded. From 2223 citations identified, 6 satisfied the inclusion/exclusion criteria. All 6 studies significantly improved at least one quality of life outcome immediately post-intervention. Significant quality of life improvements were maintained at 12-months follow-up in one out of two studies for each of the short- (0-3 months), medium- (3-12 months), and long-term (≥ 12 months) study duration categories. All 6 psychological intervention studies significantly improved at least one quality of life outcome immediately post-intervention, with three out of six studies maintaining effects up to 12-months post-intervention. Future studies should seek to assess the efficacy of tailored psychological interventions using different formats, durations and facilitators to supplement healthcare provision and practice.

  8. Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain.

    Science.gov (United States)

    Lee, Min-Young; Yu, Ji Hea; Kim, Ji Yeon; Seo, Jung Hwa; Park, Eun Sook; Kim, Chul Hoon; Kim, Hyongbum; Cho, Sung-Rae

    2013-01-01

    Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+ / Cl- -dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.

  9. Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

    Science.gov (United States)

    Maggio, Nicola; Segal, Menahem

    2011-04-15

    The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Ectopic AP4 expression induces cellular senescence via activation of p53 in long-term confluent retinal pigment epithelial cells.

    Science.gov (United States)

    Wang, Yiping; Wong, Matthew Man-Kin; Zhang, Xiaojian; Chiu, Sung-Kay

    2015-11-15

    When cells are grown to confluence, cell-cell contact inhibition occurs and drives the cells to enter reversible quiescence rather than senescence. Confluent retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as a model in this study to examine the role of overexpression of transcription factor AP4, a highly expressed transcription factor in many types of cancer, in these cells during long-term culture. We generated stable inducible RPE cell clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a large, flattened morphology and even cease proliferating; these changes were not observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4-expressing cells exhibited senescence-associated β-galactosidase activity and the senescence-associated secretory phenotype. We demonstrated that the induced cellular senescence was mediated by enhanced p53 expression and that AP4 regulates the p53 gene by binding directly to two of the three E-boxes present on the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4 in inducing p53-associated cellular senescence. Collectively, we showed that overexpression of AP4 mediates cellular senescence involving in activation of p53 in long-term post-confluent RPE cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Improved method for P and T strategy selection by long-term risk evaluation of nuclear energy systems

    International Nuclear Information System (INIS)

    Csom, G.; Feher, S.; Szieberth, M.

    2001-01-01

    The paper presents a detailed introduction of the presently used indicators of long-term risk, namely various concepts of radiotoxicity, analyses their advantages and disadvantages, and proposes further indicators called residual hazard and residual hazard index. In order to illustrate them, the time behavior of the relative radiotoxicity and the residual hazard index is investigated for a few representative cases. In the first one, conventional thermal and fast reactors, while in the second one molten salt reactors are investigated from the viewpoint of transmutation. The results shown indicate the usefulness of the application of the now proposed quantities. (author)

  12. Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

    Science.gov (United States)

    Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

    2016-12-01

    The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

  13. Antenatal maternal long-term hypoxia: acclimatization responses with altered gene expression in ovine fetal carotid arteries.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In humans and other species, long-term hypoxia (LTH during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF, and other problems. To identify the signal transduction pathways and critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified mRNA from 38 genes upregulated >2 fold (P2-fold (P<0.05. The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF binding protein 3, IGF type 2 receptor, transforming growth factor (TGF Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. Most genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3' un translated region (UTR. Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L. We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may play a role in the acclimatization response to high-altitude associated LTH.

  14. Improving long term resistance of uranium mill tailings covers to hydrologic stress using RIPRAP: a preliminary assessment

    International Nuclear Information System (INIS)

    Walters, W.H.; Skaggs, R.L.

    1980-01-01

    The long term effectiveness of riprap to protect uranium mill tailings repositories against erosion by flowing water is currently being evaluated by Pacific Northwest Laboratory for the US Nuclear Regulatory Commission. The investigation is part of a comprehensive study to determine technically justified and cost effective alternatives for armoring of radon suppression covers. As a protective cover, riprap appears to be one of the most reliable methods because of its proven durability to resist channel bed scour around bridge piers and erosion of river banks. Damage to radon suppression covers by water could occur under similar circumstances where the erosion would be due to overland flow or a large flood event. The principal mechanisms of soil erosion by water are discussed with respect to earth surfaces of mounted or flat geometries. Since long time periods on the order of one thousand years may be involved, any riprap design procedure should consider allowances for partial failures of the cover. Design procedures are summarized and both advantages and disadvantages are discussed. Problems that may occur over long term storage of mill tailings are evaluated in order to put the use of riprap in proper perspective

  15. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  16. Reduced volume and increased training intensity elevate muscle Na+/K+ pump {alpha}2-subunit expression as well as short- and long-term work capacity in humans

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Gunnarsson, Thomas Petursson; Wendell, Jesper

    2009-01-01

    was unaltered, but the 3-K (3,000 m) time was reduced (Pexpression and performance remained unaltered in CON. The present data suggest that both short- and long-term......% reduction in the amount of training but including speed endurance training consisting of 6-12 30-s sprint runs 3-4 times a week (SET, n=12) or a control group (CON, n=5), which continued the endurance training (about 55 km(.)wk(-1)). For SET the expression of the muscle Na(+)/K(+) pump alpha2-subunit was 68...

  17. Emiliania huxleyi increases calcification but not expression of calcification-related genes in long-term exposure to elevated temperature and pCO2.

    Science.gov (United States)

    Benner, Ina; Diner, Rachel E; Lefebvre, Stephane C; Li, Dian; Komada, Tomoko; Carpenter, Edward J; Stillman, Jonathon H

    2013-01-01

    Increased atmospheric pCO2 is expected to render future oceans warmer and more acidic than they are at present. Calcifying organisms such as coccolithophores that fix and export carbon into the deep sea provide feedbacks to increasing atmospheric pCO2. Acclimation experiments suggest negative effects of warming and acidification on coccolithophore calcification, but the ability of these organisms to adapt to future environmental conditions is not well understood. Here, we tested the combined effect of pCO2 and temperature on the coccolithophore Emiliania huxleyi over more than 700 generations. Cells increased inorganic carbon content and calcification rate under warm and acidified conditions compared with ambient conditions, whereas organic carbon content and primary production did not show any change. In contrast to findings from short-term experiments, our results suggest that long-term acclimation or adaptation could change, or even reverse, negative calcification responses in E. huxleyi and its feedback to the global carbon cycle. Genome-wide profiles of gene expression using RNA-seq revealed that genes thought to be essential for calcification are not those that are most strongly differentially expressed under long-term exposure to future ocean conditions. Rather, differentially expressed genes observed here represent new targets to study responses to ocean acidification and warming.

  18. Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors

    Directory of Open Access Journals (Sweden)

    Hui eHan

    2013-10-01

    Full Text Available Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER stress response in liver cancer development was investigated using an animal model with a liver knockout of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet (HFD feeding resulted in higher levels of serum alanine aminotransferase (ALT, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months knockout females than in either middle-aged (6 months knockouts or older (aged 16 months wild type females. In the older knockout females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER associated degradation (ERAD were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2, Herpud1 (ubiquitin-like domain member, Wfs1 (wolfram syndrome gene, and Yod1 (deubiquinating enzyme 1 was co-present with decreased proteasome activities, increased estrogen receptor alpha variant (ERa36, and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2 and STAT3 (the signal transducers and activators of transcription in the older knockout female fed alcohol. Our results suggest that long-term alcohol consumption and ageing may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ER associated degradation.

  19. Long-term activation of group I metabotropic glutamate receptors increases functional TRPV1-expressing neurons in mouse dorsal root ganglia

    Directory of Open Access Journals (Sweden)

    Takayoshi eMasuoka

    2016-03-01

    Full Text Available Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1 in dorsal root ganglion (DRG neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC, a transient receptor potential ankyrin type 1 (TRPA1 agonist. Increase in the proportion was suppressed by phospholipase C, protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia.

  20. Explaining the success or failure of quality improvement initiatives in long-term care organizations from a dynamic perspective.

    Science.gov (United States)

    Etheridge, Francis; Couturier, Yves; Denis, Jean-Louis; Tremblay, Lucie; Tannenbaum, Cara

    2014-09-01

    The purpose of this study was to better understand why change initiatives succeed or fail in long-term care organizations. Four case studies from Québec, Canada were contrasted retrospectively. A constipation and restraints program succeeded, while an incontinence and falls program failed. Successful programs were distinguished by the use of a change strategy that combined "let-it happen," "help-it happen," and "make-it happen" interventions to create senses of urgency, solidarity, intensity, and accumulation. These four active ingredients of the successful change strategies propelled their respective change processes forward to completion. This paper provides concrete examples of successful and unsuccessful combinations of "let-it happen," "help-it happen," and "make-it happen" change management interventions. Change managers (CM) can draw upon these examples to best tailor and energize change management strategies in their own organizations. © The Author(s) 2013.

  1. Using a book chat to improve attitudes and perceptions of long-term care staff about dementia.

    Science.gov (United States)

    Larocque, Natasha; Schotsman, Chloe; Kaasalainen, Sharon; Crawshaw, Diane; McAiney, Carrie; Brazil, Emma

    2014-05-01

    This study sought to evaluate a book chat intervention based on Lisa Genova's novel, Still Alice, to influence long-term care (LTC) staff perceptions and attitudes when caring for individuals with dementia. A qualitative descriptive design was used. Eleven participants partook in a 2.5-hour book chat at a southern Ontario LTC facility. Following the book chat, participants answered two open-ended questions to assess how the book chat influenced their views on dementia. Thematic content analysis was used to analyze the qualitative questionnaire. Content analysis of the participants' responses revealed that the book chat positively influenced their attitudes and perceptions toward dementia, particularly by providing more insight into the individual's personal struggle with the disease. Furthermore, participants found that the book chat influenced their care practices. By creating innovative learning opportunities, attitudes and perceptions about dementia care can be transcended and greatly benefit staff, family, and residents. Copyright 2014, SLACK Incorporated.

  2. ACTIVE STRATEGIES DURING INQUIRY-BASED SCIENCE TEACHER EDUCATION TO IMPROVE LONG-TERM TEACHER SELF-EFFICACY

    DEFF Research Database (Denmark)

    Evans, Robert Harry

    2012-01-01

    products, is the personal capacity belief of self- efficacy which has been shown to be important to personal behavioral change. The purpose of this research was to develop and test a model of teacher professional development (TPD) which adds specific elements for altering teacher self......-efficacies to existing FP7 IBST products. This model was tested for its usefulness in increasing participant self-efficacy as evidenced by short and long term quantitative measures as well as by evaluation of long terminquiry lessons. Workshops to promote IBST were conducted in five different countries. Each workshop...... months. The promotion of self-efficacy in TPD provides a consistent way of evaluating the impact of IBST workshops through the use of changes in self-efficacy....

  3. Effects of long-term coal supply contracts on technology adoption and improvements in the mining of coal. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Walton, D.R.; Hawkins, S.A.; Webb, P.F.; Kauffman, P.W.

    1979-08-01

    The relationship between long-term coal supply contracts and the adoption of new technology in the coal mining industry is a complex one. From this study certain conclusions can be drawn. New technologies and improvements in the mining of coal can be logically categorized into three areas: evolutionary technology, transitional technology, or innovative technology. Evolutionary improvements in technology can be categorized as improvements, or increased production capacities, in existing equipment. Transitional technology involves the adoption of existing or proven technologies into new conditions, or, proceeding from one technology type to a newer type for the same function. Innovative technology includes equipment, concepts, and systems not readily available, or untried, in the existing mining environment (seam conditions, etc.). Technology adoption is an economic decision. This point was repeatedly emphasized by industry representatives contacted during the study. The long-term coal supply contract influences the decision to adopt new technology and mining improvements in several ways depending on the technology type (i.e., evolutionary, transitional, or innovative), and also the coal supplier type (i.e., captive or independent producer). Several examples of the adoption of new technologies in mines under long-term coal supply contracts are discussed. (LTN)

  4. Helios expression and Foxp3 TSDR methylation of IFNy+ and IFNy- Treg from kidney transplant recipients with good long-term graft function.

    Directory of Open Access Journals (Sweden)

    Karina Trojan

    Full Text Available There is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient.Helios expression determined by eight-color-fluorescence flow cytometry and methylation status of the Foxp3 Treg specific demethylation region (TSDR served as indicators for stability of Foxp3 expression. Methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations originating from peripheral blood using high resolution melt analysis. A total of 136 transplant recipients and 52 healthy controls were studied.Proportions of IFNy+ Treg were similar in patients and healthy controls (0.05% and 0.04% of all CD4+ lymphocytes; p = n.s.. Patients also had similar absolute counts of IFNy producing Helios+ and Helios- Treg (p = n.s.. Most of the IFNy+ and IFNy- Treg in transplant recipients had a methylated Foxp3 TSDR, however, there was a sizeable proportion of IFNy+ and IFNy- Treg with demethylated Foxp3 TSDR. Male and female patients showed more frequently methylated IFNy+ and IFNy- Treg than male and female controls (all p<0.05.Kidney transplant recipients with good long-term stable graft function have similar levels of IFNy+ Treg as healthy controls. IFNy+ and IFNy- Treg subsets in patients consist of cells with stable and cells with transient Foxp3 expression; however, patients showed more frequently methylated IFNy+ and IFNy- Treg than controls. The data show increased levels of Treg subsets with stable as well as transient Foxp3 expression in patients with stable allograft acceptance compared to healthy controls.

  5. Perspectives for hydropower stations in Switzerland: long-term competitiveness and possibilities for improvement; Perspektiven fuer die Wasserkraftwerke in der Schweiz. Langfristige Wettbewerbsfaehigkeit und moegliche Verbesserungspotenziale

    Energy Technology Data Exchange (ETDEWEB)

    Filippini, M.; Banfi, S. [Istituto di Microeconomia e Economia Pubblica, MecoP, Universita della Svizzera Italiana, Lugano (Switzerland); Luchsinger, C.; Wild, J.; Balmer, M.; Grand, D.; Henkels, L.; Semadeni, M. [Swiss Federal Institute of Technology (ETHZ), Centre for Energy Policy and Economics (CEPE), Zuerich (Switzerland); Gnansounou, E. [Swiss Federal Institute of Technology (EPFL), Laboratoire de systemes energetiques (LASEN), Lausanne (Switzerland)

    2001-07-01

    This first general study - which has the character of a preliminary study - examines the questions if the liberalisation of the electricity market will have a negative effect on the competitiveness of hydropower in the long-term and what measures can be taken against such effects. Long-term competitiveness is defined as the ability of a business in this sector to make investments in renewal in the long-term, i.e. after its concessions have expired. The three main aims of the study are: 1. Assessment of the long-term competitiveness of the sector and identification of the factors which could either have a negative effect on it or improve it, 2. Analysis of cost structures and presentation of measures through which the long-term competitiveness of the sector can be reinforced, 3. Presentation of possible political measures to be taken in this business area in order to improve the long-term competitiveness of hydropower stations. The study identifies the most important factors that determine future competitiveness as being the market prices for electricity and capital costs (depreciation and interest on own and borrowed capital). Further, water fees, taxes and regulations concerning residual water flow can be of great importance for investment decisions, in particular for those enterprises that operate close to their profitability limits. The results of the analysis indicate that, in the future, a considerable number of enterprises must be reckoned with that will refrain from renewing their plant. Such outcomes depend, of course, on developments in electricity market prices, specific investment costs, rates of interest and other economic, political, and legal conditions. Making a prognosis about the development of such parameters is linked with a high degree of uncertainty. By means of sensitivity calculations and the definition of various scenarios, attempts are made to take these uncertainties into account . Finally, the study makes reference to the fact that

  6. The Effectiveness of Singing or Playing a Wind Instrument in Improving Respiratory Function in Patients with Long-Term Neurological Conditions: A Systematic Review.

    Science.gov (United States)

    Ang, Kexin; Maddocks, Matthew; Xu, Huiying; Higginson, Irene J

    2017-03-01

    Many long-term neurological conditions adversely affect respiratory function. Singing and playing wind instruments are relatively inexpensive interventions with potential for improving respiratory function; however, synthesis of current evidence is needed to inform research and clinical use of music in respiratory care. To critically appraise, analyze, and synthesize published evidence on the effectiveness of singing or playing a wind instrument to improve respiratory function in people with long-term neurological conditions. Systematic review of published randomized controlled trials and observational studies examining singing or playing wind instruments to improve respiratory function in individuals with long-term neurological conditions. Articles meeting specified inclusion criteria were identified through a search of the Medline, Embase, PsycINFO, Cochrane Library, CINAHL, Web of Science, CAIRSS for Music, WHO International Clinical Trials Registry Platform Search Portal, and AMED databases as early as 1806 through March 2015. Information on study design, clinical populations, interventions, and outcome measures was extracted and summarized using an electronic standardized coding form. Methodological quality was assessed and summarized across studies descriptively. From screening 584 references, 68 full texts were reviewed and five studies included. These concerned 109 participants. The studies were deemed of low quality, due to evidence of bias, in part due to intervention complexity. No adverse effects were reported. Overall, there was a trend toward improved respiratory function, but only one study on Parkinson's disease had significant between-group differences. The positive trend in respiratory function in people with long-term neurological conditions following singing or wind instrument therapy is of interest, and warrants further investigation. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  7. Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function.

    Science.gov (United States)

    Kołodziejski, Paweł A; Pruszyńska-Oszmałek, Ewa; Strowski, Mathias Z; Nowak, Krzysztof W

    2017-06-01

    Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover, obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus.

  8. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

    KAUST Repository

    Tadi, Monika; Allaman, Igor; Lengacher, Sylvain; Grenningloh, Gabriele; Magistretti, Pierre J.

    2015-01-01

    We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  9. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

    Directory of Open Access Journals (Sweden)

    Monika Tadi

    Full Text Available We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4, alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  10. Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory

    KAUST Repository

    Tadi, Monika

    2015-10-29

    We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

  11. Cdk7 Is Required for Activity-Dependent Neuronal Gene Expression, Long-Lasting Synaptic Plasticity and Long-Term Memory

    Directory of Open Access Journals (Sweden)

    Guiqin He

    2017-11-01

    Full Text Available In the brain, de novo gene expression driven by learning-associated neuronal activities is critical for the formation of long-term memories. However, the signaling machinery mediating neuronal activity-induced gene expression, especially the rapid transcription of immediate-early genes (IEGs remains unclear. Cyclin-dependent kinases (Cdks are a family of serine/threonine kinases that have been firmly established as key regulators of transcription processes underling coordinated cell cycle entry and sequential progression in nearly all types of proliferative cells. Cdk7 is a subunit of transcriptional initiation factor II-H (TFIIH and the only known Cdk-activating kinase (CAK in metazoans. Recent studies using a novel Cdk7 specific covalent inhibitor, THZ1, revealed important roles of Cdk7 in transcription regulation in cancer cells. However, whether Cdk7 plays a role in the regulation of transcription in neurons remains unknown. In this study, we present evidence demonstrating that, in post-mitotic neurons, Cdk7 activity is positively correlated with neuronal activities in cultured primary neurons, acute hippocampal slices and in the brain. Cdk7 inhibition by THZ1 significantly suppressed mRNA levels of IEGs, selectively impaired long-lasting synaptic plasticity induced by 4 trains of high frequency stimulation (HFS and prevented the formation of long-term memories.

  12. Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells.

    Science.gov (United States)

    Wang, Yiping; Cheng, Xiangdong; Samma, Muhammad Kaleem; Kung, Sam K P; Lee, Clement M; Chiu, Sung Kay

    2018-06-01

    c-Myc is a highly pleiotropic transcription factor known to control cell cycle progression, apoptosis, and cellular transformation. Normally, ectopic expression of c-Myc is associated with promoting cell proliferation or triggering cell death via activating p53. However, it is not clear how the levels of c-Myc lead to different cellular responses. Here, we generated a series of stable RPE cell clones expressing c-Myc at different levels, and found that consistent low level of c-Myc induced cellular senescence by activating AP4 in post-confluent RPE cells, while the cells underwent cell death at high level of c-Myc. In addition, high level of c-Myc could override the effect of AP4 on cellular senescence. Further knockdown of AP4 abrogated senescence-like phenotype in cells expressing low level of c-Myc, and accelerated cell death in cells with medium level of c-Myc, indicating that AP4 was required for cellular senescence induced by low level of c-Myc.

  13. Unregulated provider perceptions of audit and feedback reports in long-term care: cross-sectional survey findings from a quality improvement intervention.

    Science.gov (United States)

    Fraser, Kimberly D; O'Rourke, Hannah M; Baylon, Melba Andrea B; Boström, Anne-Marie; Sales, Anne E

    2013-02-13

    Audit with feedback is a moderately effective approach for improving professional practice in other health care settings. Although unregulated caregivers give the majority of direct care in long-term care settings, little is known about how they understand and perceive feedback reports because unregulated providers have not been directly targeted to receive audit with feedback in quality improvement interventions in long-term care. The purpose of this paper is to describe unregulated care providers' perceptions of usefulness of a feedback report in four Canadian long-term care facilities. We delivered monthly feedback reports to unregulated care providers for 13 months in 2009-2010. The feedback reports described a unit's performance in relation to falls, depression, and pain as compared to eight other units in the study. Follow-up surveys captured participant perceptions of the feedback report. We conducted descriptive analyses of the variables related to participant perceptions and multivariable logistic regression to assess the association between perceived usefulness of the feedback report and a set of independent variables. The vast majority (80%) of unregulated care providers (n = 171) who responded said they understood the reports. Those who discussed the report with others and were interested in other forms of data were more likely to find the feedback report useful for making changes in resident care. This work suggests that unregulated care providers can understand and feel positively about using audit with feedback reports to make changes to resident care. Further research should explore ways to promote fuller engagement of unregulated care providers in decision-making to improve quality of care in long-term care settings.

  14. Changes in mu-opioid receptor expression and function in the mesolimbic system after long-term access to a palatable diet.

    Science.gov (United States)

    Pitman, Kimberley A; Borgland, Stephanie L

    2015-10-01

    The incidence of obesity in both adults and children is rising. In order to develop effective treatments for obesity, it is important to understand how diet can induce changes in the brain that could promote excessive intake of high-calorie foods and alter the efficacy of therapeutic targets. The mu-opioid receptor is involved in regulating the motivation for and hedonic reaction to food. Here, we review the literature examining changes in the expression and function of mu-opioid receptors in the mesolimbic system of rodents after extended access to a high-fat diet. We also review how maternal diet can induce long-term changes in the expression or function of mu-opioid receptors in the mesolimbic system of offspring. Understanding the behavioural and therapeutic implications of these changes requires further study. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S.

    Science.gov (United States)

    Fic, A; Mlakar, S Jurković; Juvan, P; Mlakar, V; Marc, J; Dolenc, M Sollner; Broberg, K; Mašič, L Peterlin

    2015-08-01

    The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10 nM BPA, BPAF, or BPS, for 8 h and 3 months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). 'Embryonic skeletal system development' was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the 'isoprenoid biosynthetic process' was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Active intervention in patients with whiplash-associated disorders improves long-term prognosis: a randomized controlled clinical trial.

    Science.gov (United States)

    Rosenfeld, Mark; Seferiadis, Aris; Carlsson, Jane; Gunnarsson, Ronny

    2003-11-15

    Three-year follow-up of a prospective randomized trial in 97 patients exposed to whiplash trauma in motor vehicle collisions. To compare the long-term efficacy of active intervention with that of standard intervention and the effect of early versus delayed initiation of intervention. There is no strong evidence for many treatments for whiplash-associated disorders. Some studies provide weak evidence supporting active intervention. Patients were randomized to an intervention using frequent active cervical rotation complemented by assessment and treatment according to McKenzie's principles or to a standard intervention of initial rest, recommended soft collar, and gradual self-mobilization. To test the time factor, interventions were either made within 96 hours or delayed 14 days from collision. The effects of the two interventions and the time factor on pain intensity, cervical range of motion, and sick leave were analyzed at 6 months and 3 years. Cervical range of motion at 3 years was also compared with that in matched, unexposed individuals. Pain intensity and sick leave were significantly (P whiplash-associated disorders, active intervention is more effective in reducing pain intensity and sick leave, and in retaining/regaining total range of motion than a standard intervention. Active intervention can be carried out as home exercises initiated and supported by appropriately trained health professionals.

  17. Neuraxial anesthesia improves long-term survival after total joint replacement: a retrospective nationwide population-based study in Taiwan.

    Science.gov (United States)

    Chen, Wei-Hung; Hung, Kuo-Chuan; Tan, Ping-Heng; Shi, Hon-Yi

    2015-04-01

    This study explored the effects of general (GA) and neuraxial (NA) anesthesia on the outcomes of primary total joint replacement (TJR) in terms of postoperative mortality, length of stay (LOS), and hospital treatment costs. From 1997 to 2010, this nationwide population-based study retrospectively evaluated 7,977 patients in Taiwan who underwent primary total hip or knee replacement. We generated two propensity-score-matched subgroups, each containing an equal number of patients who underwent TJR with either GA or NA. Of the 7,977 patients, 2,990 (37.5%) underwent GA and 4,987 (62.5%) underwent NA. Propensity-score matching was used to create comparable GA and NA groups adjusted for age, sex, comorbidities, surgery type, hospital volume, and surgeon volume. Survival over the first three years following surgery was similar. The proportion of patients alive up to 14 years postoperatively for those undergoing NA was 58.2% (95% confidence interval [CI] 50.4 to 66.0), and for those undergoing GA it was 57.3% (95% CI 51.4 to 63.2). Neuraxial anesthesia was associated with lower median [interquartile range; IQR] hospital treatment cost ($4,079 [3,805-4,444] vs $4,113 [3,812-4,568]; P anesthesia costs are removed. The mechanism underlying the association between NA and long-term survival is unknown.

  18. Animation-Based Teaching of Semiconductor Devices: Long-Term Improvement in Students’ Achievements in a Two-Year College

    Directory of Open Access Journals (Sweden)

    Aharon Gero

    2015-02-01

    Full Text Available The structure and operating principle of semiconductor devices are a central topic in teaching electronics, both in universities and in two-year colleges. Teachers teaching this subject normally run into substantial difficulties stemming from the fact that a major part of the concepts and processes that are relevant to understanding these devices are abstract. In light of the advantages of multimedia in illustrating dynamic processes, the chapter covering the field effect transistor (FET has recently been taught through animation at a two-year college in Israel. The study presented here has examined, through quantitative tools, whether animation-based teaching of the FET had any effect on students’ achievements in the subject of basic electronic devices. Forty electronics students have participated in the study. Its findings indicate that in the short and long term alike, the achievements of students who studied the transistor through animation were significantly higher than those of their peers who studied it through a traditional method. Additionally, the effect size was very large.

  19. Improvement of the long term stability in the high temperature solid oxide fuel cell using functional layers

    Energy Technology Data Exchange (ETDEWEB)

    Brueckner, B.; Guenther, C.; Ruckdaeschel, R. [Siemens AG, Erlangen (Germany)] [and others

    1996-12-31

    In the planar Siemens design of the solid oxide fuel cell a metallic interconnector is used to seperate the ceramic single cells. A disadvantage of the metallic bipolar plate which consists of a chromium alloy is the formation of high volatile Cr-oxides and hydroxides at the surface at the cathode side. The reaction products evaporate and are reduced at the cathode/electrolyte interface to form new crystalline phases. This process gives rise to long term cell degradation. Protective coatings might be successful in preventing the chromium oxide evaporation. The required properties of the protective layers are (I) high electrical conductivity, (II) similar coefficients of thermal expansion to the bipolar plate (III), chemical compatibility to the bipolar plate and cathode material, (IV) a low diffusion coefficient of Cr and (V) chemical stability up to 1223K under oxygen atmosphere. Furthermore, during operation at 1223K an electrical contact between the metallic plate and the electrodes has to be maintained. This problem could be solved using ceramic layer between the metallic plate and the single cells.

  20. Communication training improves sense of performance expectancy of public health nurses engaged in long-term elderly prevention care program.

    Science.gov (United States)

    Tanabe, Motoko; Suzukamo, Yoshimi; Tsuji, Ichiro; Izumi, Sin-Ichi

    2012-01-01

    This study examines the effectiveness of a communication skill training based on a coaching theory for public health nurses (PHNs) who are engaged in Japan's long-term care prevention program. The participants in this study included 112 PHNs and 266 service users who met with these PHNs in order to create a customized care plan within one month after the PHNs' training. The participants were divided into three groups: a supervised group in which the PHNs attended the 1-day training seminar and the follow-up supervision; a seminar group attended only the 1-day training seminar; a control group. The PHNs' sense of performance expectancy, and user's satisfaction, user's spontaneous behavior were evaluated at the baseline (T1), at one month (T2), and at three months (T3) after the PHNs' training. At T3, the PHNs performed a recalled evaluation (RE) of their communication skills before the training. The PHNs' sense of performance expectancy increased significantly over time in the supervised group and the control group (F = 11.28, P < 0.001; F = 4.03, P < 0.05, resp.). The difference score between T3-RE was significantly higher in the supervised group than the control group (P < 0.01). No significant differences in the users' outcomes were found.

  1. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    Science.gov (United States)

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

    Science.gov (United States)

    Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

    2018-04-05

    Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I and a more variable phase (stage-II. We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

  4. Digital gene expression analysis in the gills of Ruditapes philippinarum exposed to short- and long-term exposures of ammonia nitrogen.

    Science.gov (United States)

    Cong, Ming; Wu, Huifeng; Cao, Tengfei; Lv, Jiasen; Wang, Qing; Ji, Chenglong; Li, Chenghua; Zhao, Jianmin

    2018-01-01

    Previous study revealed severe toxic effects of ammonia nitrogen on Ruditapes philippinarum including lysosomal instability, disturbed metabolic profiles, gill tissues with damaged structure, and variation of neurotransmitter concentrations. However, the underlying molecular mechanism was not fully understood yet. In the present study, digital gene expression technology (DGE) was applied to globally screen the key genes and pathways involved in the responses to short- and long-term exposures of ammonia nitrogen. Results of DGE analysis indicated that short-term duration of ammonia exposure affected pathways in Dorso-ventral axis formation, Notch signaling, thyroid hormone signaling and protein processing in endoplasmic reticulum. The long-term exposure led to DEGs significantly enriched in gap junction, immunity, signal and hormone transduction, as well as key substance metabolism pathways. Functional research of significantly changed DEGs suggested that the immunity of R. philippinarum was weakened heavily by toxic effects of ammonia nitrogen, as well as neuro-transduction and metabolism of important substances. Taken together, the present study provides a molecular support for the previous results of the detrimental toxicity of ammonia exposure in R. philippinarum, further work will be performed to investigate the specific genes and their certain functions involved in ammonia toxicity to molluscs. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  6. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

    Directory of Open Access Journals (Sweden)

    Young-Mi Lim

    Full Text Available Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1 is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1 and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.

  7. Long-term application of bioorganic fertilizers improved soil biochemical properties and microbial communities of an apple orchard soil

    Directory of Open Access Journals (Sweden)

    Wang Lei

    2016-11-01

    Full Text Available Soil biochemical properties and microbial communities are usually considered as important indicators of soil health because of their association with plant nutrition. In this study, we investigated the impact of long-term application of bioorganic fertilizer (BOF on soil biochemical properties and microbial communities in the apple orchard soil of the Loess Plateau. The experiment included three treatments: (1 control without fertilization (CK; (2 chemical fertilizer application (CF; and (3 bioorganic fertilizer application (BOF. The high throughput sequencing was used to examine the bacterial and fungal communities in apple orchard soil. The results showed that the BOF treatment significantly increased the apple yield during the experimental time (2009-2015. The application of BOF significantly increased the activities of catalase and invertase compared to those in CK and CF treatments. The high throughput sequencing data showed that the application of BOF changed the microbial community composition of all soil depths considered (0-20cm, 20-40cm, and 40-60cm, e.g., the relative abundance of bio-control bacteria (Xanthomonadales, Lysobacter, Pseudomonas and Bacillus, Proteobacteria, Bacteroidetes, Ohtaekwangia, Ilyonectria and Lecanicillium was increased while that of Acidobacteria, Chloroflexi, Gp4, Gp6 and Sphaerobacter was decreased. The increase in apple yield after the application of BOF might be due to increase in organic matter, total nitrogen and catalase and invertase activities of soil and change in the bacterial community composition by enriching Bacillus, Pseudomonas, Lysobacter and Ohtaekwangia. These results further enhance the understanding on how BOFs alter soil microbial community composition to stimulate soil productivity.

  8. Improving the care of people with long-term conditions in primary care: protocol for the ENHANCE pilot trial

    Directory of Open Access Journals (Sweden)

    Emma L. Healey

    2015-12-01

    Full Text Available Background: Long-term conditions (LTCs are important determinants of quality of life and healthcare expenditure worldwide. Whilst multimorbidity is increasingly the norm in primary care, clinical guidelines and the delivery of care remain focused on single diseases, resulting in poorer clinical outcomes. Osteoarthritis, and anxiety and/or depression frequently co-occur with other LTCs, yet are seldom prioritized by the patient or clinician, resulting in higher levels of disability, poorer prognosis, and increased healthcare costs. Objective: To examine the feasibility and acceptability of an integrated approach to LTC management, tackling the under-diagnosis and under-management of osteoarthritis-related pain and anxiety and/or depression in older adults with other LTCs in primary care. Design: The ENHANCE study is a pilot stepped-wedge cluster randomized controlled trial to test the feasibility and acceptability of a nurse-led ENHANCE LTC review consultation for identifying, assessing, and managing joint pain, and anxiety and/or depression in patients attending LTC reviews. Specific objectives (process evaluation and research outcomes will be achieved through a theoretically informed mixed-methods approach using participant self-reported questionnaires, a medical record review, an ENHANCE EMIS template, qualitative interviews, and audio recordings of the ENHANCE LTC review. Discussion: Success of the pilot trial will be measured against the level of the primary care team engagement, assessment of training delivery, and degree of patient recruitment and retention. Patient satisfaction and treatment fidelity will also be explored. ISRCTN registry number: 12154418. Journal of Comorbidity 2015;5(1:135–149

  9. Acute suppression, but not chronic genetic deficiency, of c-fos gene expression impairs long-term memory in aversive taste learning.

    Science.gov (United States)

    Yasoshima, Yasunobu; Sako, Noritaka; Senba, Emiko; Yamamoto, Takashi

    2006-05-02

    Several lines of evidence have indicated that the establishment of long-term memory requires protein synthesis, including the synthesis of immediate-early gene products. Although the anatomical expression patterns of the c-fos gene, a transcription factor-encoding immediate-early gene, in conditioned taste aversion (CTA) are well documented, the functional roles of c-fos gene expression and Fos-mediated transcription remain to be clarified. Using the antisense oligodeoxynucleotide (AS-ODN) method in rats and gene-targeting knockout techniques in mice (c-fos(-/-) mice), we examined the roles of c-fos gene expression in the acquisition, retrieval, and retention of CTA. Preconditioning microinfusion of AS-ODN directed against c-fos mRNA (c-fos AS-ODN) into the parabrachial nucleus (PBN) impaired the acquisition, whereas infusion of control ODNs consisting of a randomized or inverted base order had no effect. Microinfusion of c-fos AS-ODN into either the amygdala or insular cortex did not impair the acquisition, whereas it attenuated the retention. Retrieval and subsequent retention of an acquired CTA were not disrupted by c-fos AS-ODN infusion into the PBN or amygdala. Microinfusion of another AS-ODN directed against zif268 (egr-1, krox-24, NGFI-A) mRNA into the PBN or amygdala did not affect the acquisition and retention. The genetic deficiency in c-fos(-/-) mice caused normal acquisition and retention. The present results suggest that the Fos-mediated gene transcription in the PBN, amygdala, or insular cortex plays critical roles in the acquisition and/or consolidation, but not the retrieval, of long-term taste memory; nevertheless, some other factors could compensate CTA mechanism when Fos-mediated transcription is not available.

  10. Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency.

    Science.gov (United States)

    Kuang, Qi; Zhang, Sheng; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2017-01-01

    Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA-GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions.

  11. Long-term recognition memory of individual conspecifics is associated with telencephalic expression of Egr-1 in the electric fish Apteronotus leptorhynchus.

    Science.gov (United States)

    Harvey-Girard, Erik; Tweedle, Jessica; Ironstone, Joel; Cuddy, Martin; Ellis, William; Maler, Leonard

    2010-07-15

    Primates and songbirds can learn to recognize individual conspecifics based on complex sensory cues; this requires a large, highly differentiated dorsal telencephalon. Here we show that the electric fish Apteronotus leptorhynchus can learn to recognize individual conspecifics based on a simple cue, the beat frequency of their summed sinusoidal electric organ discharges (EOD). Male fish produce transient communication signals (chirps) in response to mimic EODs. The chirp response habituates over repeated stimulus presentations within one experimental session, continues to habituate over successive daily sessions and is nearly extinguished after 5-7 days. Habituation of the chirp response was specific to the presented beat frequency. The conversion of short- to long-term habituation could be disrupted by cooling the head 30 minutes after the daily habituation trials. Consolidation of long-term memory in mammals is thought to involve induced expression of an immediate early gene, Egr-1. We cloned the Apteronotid homolog of the Egr-1 gene and found that chirp-evoking stimuli induced strong expression of its mRNA within the dorsal (Dd), central (DC), and lateral (DL) subdivisions of the dorsal telencephalon. Interestingly, the dorsolateral region is hypothesized to be homologous to the amniote hippocampal formation. We conclude that A. leptorhynchus can learn to identify individual conspecifics based on their EOD frequency and can remember these frequencies for several days. We hypothesize that this form of learning, as in primates and songbirds, requires a subset of dorsal telencephalic areas and involves a consolidation-like process that includes the expression of the transcription factor AptEgr-1.

  12. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    Directory of Open Access Journals (Sweden)

    Vladimir O. Pustylnyak

    2015-01-01

    Full Text Available Gene expression plays an important role in the mechanisms of long-term potentiation (LTP, which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity.

  13. Flt3 ligand-eGFP-reporter expression characterizes functionally distinct subpopulations of CD150+ long-term repopulating murine hematopoietic stem cells.

    Science.gov (United States)

    Tornack, Julia; Kawano, Yohei; Garbi, Natalio; Hämmerling, Günter J; Melchers, Fritz; Tsuneto, Motokazu

    2017-09-01

    The pool of hematopoietic stem cells (HSCs) in the bone marrow is a mixture of resting, proliferating, and differentiating cells. Long-term repopulating HSCs (LT-HSC) are routinely enriched as Lin - Sca1 + c-Kit + CD34 - Flt3 - CD150 + CD48 - cells. The Flt3 ligand (Flt3L) and its receptor Flt3 are important regulators of HSC maintenance, expansion and differentiation. Using Flt3L-eGFP reporter mice, we show that endogenous Flt3L-eGFP-reporter RNA expression correlates with eGFP-protein expression. This Flt3L-eGFP-reporter expression distinguishes two LT-HSC populations with differences in gene expressions and reconstituting potential. Thus, Flt3L-eGFP-reporter low cells are identified as predominantly resting HSCs with long-term repopulating capacities. In contrast, Flt3L-eGFP-reporter high cells are in majority proliferating HSCs with only short-term repopulating capacities. Flt3L-eGFP-reporter low cells express hypoxia, autophagy-inducing, and the LT-HSC-associated genes HoxB5 and Fgd5, while Flt3L-eGFP-reporter high HSCs upregulate genes involved in HSC differentiation. Flt3L-eGFP-reporter low cells develop to Flt3L-eGFP-reporter high cells in vitro, although Flt3L-eGFP-reporter high cells remain Flt3L-eGFP-reporter high . CD150 + Flt3L-eGFP-reporter low cells express either endothelial protein C receptor (EPCR) or CD41, while Flt3L-eGFP-reporter high cells do express EPCR but not CD41. Thus, FACS-enrichment of Flt3/ Flt3L-eGFP-reporter negative, Lin - CD150 + CD48 - EPCR + CD41 + HSCs allows a further 5-fold enrichment of functional LT-HSCs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure

    DEFF Research Database (Denmark)

    Olsen, A. K.; Salomonsson, M.; Sørensen, C. M.

    + channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone. Only scarce information is available on the role of K+ transporters in pathophysiological mechanisms induced by long-term feeding of laboratory rats with either high-fat, high-fructose or high-fat/high-fructose...... diet. HYPOTHESIS: A 28-week diet consisting of high-fat or high-fructose, or both, will lead to changes in K+ transporter expression and function, which will be linked with changes in blood pressure, arterial smooth muscle function, endothelial function and passive structural/mechanical properties....... METHODS: Male Sprague Dawley rats (4 weeks) were randomized into 4 diet groups receiving a diet with normal chow (CTR, N=19), high-fat chow (60% saturated fat, FAT, N=18), high-fructose (10% in drinking water; FRUC, N=15), or a combination of fat/fructose (FAT/FRUC, N=15) for 28 weeks. Systolic blood...

  15. Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels

    DEFF Research Database (Denmark)

    Gradel, Anna Katrina Jógvansdóttir; Salomonsson, Max; Sørensen, Charlotte Mehlin

    2018-01-01

    in long-term diet-induced hypertension in rats. Hypothesis: A 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Methods and Results: Male Sprague Dawley rats......RNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries. BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of SKCa, IKCa, and Kir2.1 K+ channels were reduced in the High Fat/Fruc group. Reduced EDH......-type relaxation to acetylcholine was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all experimental diet groups. Conclusions: Reduced expression and function of SKCa, IKCa and Kir2.1 channels is associated with elevated blood pressure in rats fed...

  16. Making Learning Last: Teachers' Long-Term Retention of Improved Nature of Science Conceptions and Instructional Rationales

    Science.gov (United States)

    Mulvey, Bridget K.; Bell, Randy L.

    2017-01-01

    Despite successful attempts to improve learners' nature of science (NOS) conceptions through explicit, reflective approaches, retention of improved conceptions is rarely addressed in research. The issue of context for NOS instruction has implications for this retention. Whether to contextualise has been the question occupying science educators'…

  17. Visual Input Enhancement via Essay Coding Results in Deaf Learners' Long-Term Retention of Improved English Grammatical Knowledge

    Science.gov (United States)

    Berent, Gerald P.; Kelly, Ronald R.; Schmitz, Kathryn L.; Kenney, Patricia

    2009-01-01

    This study explored the efficacy of visual input enhancement, specifically "essay enhancement", for facilitating deaf college students' improvement in English grammatical knowledge. Results documented students' significant improvement immediately after a 10-week instructional intervention, a replication of recent research. Additionally, the…

  18. Long-Term Pain Treatment Did Not Improve Sleep in Nursing Home Patients with Comorbid Dementia and Depression: A 13-Week Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Kjersti M. Blytt

    2018-02-01

    Full Text Available Objective: Previous research indicates that pain treatment may improve sleep among nursing home patients. We aimed to investigate the long-term effect of pain treatment on 24-h sleep patterns in patients with comorbid depression and dementia.Design: A 13-week, multicenter, parallel-group, double-blind, placebo-controlled randomized clinical trial conducted between August 2014 and September 2016.Setting: Long-term patients from 47 nursing homes in Norway.Participants: We included 106 patients with comorbid dementia and depression according to the Mini Mental Status Examination (MMSE and the Cornell Scale for Depression in Dementia (CSDD.Intervention: Patients who were not using analgesics were randomized to receive either paracetamol (3 g/day or placebo tablets. Those who already received pain treatment were randomized to buprenorphine transdermal system (maximum 10 μg/h/7 days or placebo transdermal patches.Measurements: Sleep was assessed continuously for 7 days by actigraphy, at baseline and in week 13. Total sleep time (TST, sleep efficiency (SE, sleep onset latency (SOL, wake after sleep onset (WASO, early morning awakening (EMA, and number of wake bouts (NoW were evaluated. In addition, daytime total sleep time (DTS was estimated. Pain was assessed with Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2.Results: The linear mixed model analyses for TST, SE, SOL, WASO, EMA, NoW and DTS showed no statistically significant differences between patients who received active pain treatment and those who received placebo. Post hoc subgroup analyses showed that there were no statistically significant differences between active treatment and placebo from baseline to week 13 in patients who were in pain (MOBID-2 ≥ 3 at baseline, or in patients who had poor sleep (defined as SE < 85% at baseline. Patients who received active buprenorphine showed an increase in TST and SE compared to those who received active paracetamol

  19. Simulation-based medical education training improves short and long-term competency in, and knowledge of central venous catheter insertion: A before and after intervention study.

    Science.gov (United States)

    Cartier, Vanessa; Inan, Cigdem; Zingg, Walter; Delhumeau, Cecile; Walder, Bernard; Savoldelli, Georges L

    2016-08-01

    Multimodal educational interventions have been shown to improve short-term competency in, and knowledge of central venous catheter (CVC) insertion. To evaluate the effectiveness of simulation-based medical education training in improving short and long-term competency in, and knowledge of CVC insertion. Before and after intervention study. University Geneva Hospital, Geneva, Switzerland, between May 2008 and January 2012. Residents in anaesthesiology aware of the Seldinger technique for vascular puncture. Participants attended a half-day course on CVC insertion. Learning objectives included work organization, aseptic technique and prevention of CVC complications. CVC insertion competency was tested pretraining, posttraining and then more than 2 years after training (sustainability phase). The primary study outcome was competency as measured by a global rating scale of technical skills, a hand hygiene compliance score and a checklist compliance score. Secondary outcome was knowledge as measured by a standardised pretraining and posttraining multiple-choice questionnaire. Statistical analyses were performed using paired Student's t test or Wilcoxon signed-rank test. Thirty-seven residents were included; 18 were tested in the sustainability phase (on average 34 months after training). The average global rating of skills was 23.4 points (±SD 4.08) before training, 32.2 (±4.51) after training (P Simulation-based medical education training was effective in improving short and long-term competency in, and knowledge of CVC insertion.

  20. Long-term changes in collagen formation expressed by serum carboxyterminal propeptide of type-I procollagen and relation to left ventricular function after acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Høst, N B; Egstrup, K

    2001-01-01

    and prognosis following acute myocardial infarction (AMI). Forty-eight consecutive patients with their first AMI and 15 control subjects were studied. Patients with AMI were stratified according to the changes in s-PICP levels between days 1 and 90 (DeltaPICP) and divided into group I with ...The purpose of this study was to investigate the long-term sequential changes in serum levels of the carboxyterminal propeptide of type-I procollagen (s-PICP), which is a marker of type-I collagen synthesis, and to assess its clinical value in relation to left ventricular (LV) function....../l or group II with >16.0 microg/l. Patients in group II were characterized by LV dilatation, no improvement in ejection fraction and development of impaired diastolic filling from day 1 to 360, findings which were in contrast to group I. Cox regression analysis identified changes in s-PICP of >16.0 microg...

  1. Recognition and management of depression in skilled-nursing and long-term care settings: evolving targets for quality improvement.

    Science.gov (United States)

    Boyle, Vicki L; Roychoudhury, Canopy; Beniak, Renee; Cohn, Lisa; Bayer, Albert; Katz, Ira

    2004-01-01

    Depression is a common disorder associated with suffering, morbidity, and mortality in nursing home residents. It is treatable, and improving the quality of treatment can have a major impact. MPRO, Michigan's Quality Improvement Organization, initiated a quality-improvement project in 14 nursing facilities to improve the accuracy of assessments, targeting, and monitoring of care. Electronic Minimum Data Set (MDS) data and medical-record abstraction results were combined to form the analytic dataset. Findings from the baseline phase demonstrated that, according to medical and administrative records, 26% of newly admitted nursing home residents had symptoms of depression that were apparent at admission, and an additional 12% were recognized early in their stay. Eighty-one percent of residents with depression were receiving treatment on admission to the facility, and 79% of those with depression recognized by Day 14 were treated by then. These data demonstrate progress toward improving the initiation of treatment for depression in nursing homes; however, there are still opportunities for improving the quality of care and, especially, the quality of assessments. The authors recommend the addition of the Geriatric Depression Scale to the federally mandated MDS for cognitively intact patients. There could also be mechanisms to ensure that providers and facilities follow recommended practice guidelines. Initiating treatment with antidepressant medications should be followed with monitoring of residents to identify those who still have depressive symptoms and to modify or intensify their treatment.

  2. Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA rats.

    Directory of Open Access Journals (Sweden)

    Karen Schellong

    Full Text Available BACKGROUND: Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and 'diabesity' risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. METHODS AND FINDINGS: By rearing in normal (NL vs. small litters (SL, small-for-gestational-age (SGA rats were neonatally exposed to either normal (SGA-in-NL or over-feeding (SGA-in-SL, and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL. SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60, as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all p<0.05, and hyperphagia under normal chow as well as high-energy/high-fat diet, modelling modern 'westernized' lifestyle, were observed only in SGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (p<0.05. Lasercapture microdissection (LMD-based neuropeptide expression analyses in single neuron pools of the arcuate hypothalamic nucleus (ARC revealed a significant shift towards down-regulation of the anorexigenic melanocortinergic system (proopiomelanocortin, Pomc in SGA-in-SL rats (p<0.05. Neuropeptide expression within the orexigenic system (neuropeptide Y (Npy, agouti-related-peptide (Agrp and galanin (Gal was not significantly altered. In essence, the 'orexigenic index', proposed here as a neuroendocrine 'net-indicator', was increased in SGA-in-SL regarding Npy/Pomc expression (p<0.01, correlated to food intake (p<0.05. CONCLUSION: Adult SGA rats developed increased 'diabesity' risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding

  3. Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, Michael H; Fossum, Eigil; Høieggen, Aud

    2005-01-01

    Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...... insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction....

  4. Long-term manure applications improve soil productivity and sustain high crop yield for acidic red soils

    Science.gov (United States)

    Intensive use of chemical nitrogen (N) fertilizers has resulted in severely reduced productivity of red soils (Ferralic Cambisol) due to accelerated acidification. Manure has been shown to be effective in improving soil productivity by preventing or reversing the acidification process, but little in...

  5. General Exercise Does Not Improve Long-Term Pain and Disability in Individuals With Whiplash-Associated Disorders: A Systematic Review.

    Science.gov (United States)

    Griffin, Alexandra; Leaver, Andrew; Moloney, Niamh

    2017-07-01

    Study Design Systematic review of randomized controlled trials. Background General exercise, defined as purposeful physical activity involving repetitive exercises and incorporating multiple muscle groups, is frequently used in the management of whiplash-associated disorders (WADs). Evidence supporting its efficacy is not well established. Objectives To determine whether general exercise is effective in reducing pain and disability in people with WAD. Methods Studies published in English in peer-reviewed journals between January 1990 and May 2015 were eligible if they evaluated a general exercise intervention compared with a different intervention or control. Studies were required to evaluate pain and disability at medium-term (6-14 weeks) and long-term (52 weeks) follow-ups. The mean ± SD and sample size were recorded for follow-up scores and for change scores from baseline to follow-up. Results Of the 3 high-quality studies that were eligible for inclusion, none investigated general exercise alone. There were no clinically meaningful differences between comprehensive exercise programs, which included general exercise, and minimal intervention controls in the medium and long term. No studies directly compared general exercise with a no-treatment control. All included studies used different control interventions, preventing meta-analysis. Conclusion A lack of significant long-term improvements from general exercise interventions in individuals with WAD was identified. This finding differs from the positive benefits of general exercise for other musculoskeletal conditions. This may, in part, relate to the complexity of whiplash conditions. This may also reflect the challenge of exercise prescription in this population, where the need for sufficient intensity is balanced against the impact that exercise has on pain. Level of Evidence Therapy, level 1a. J Orthop Sports Phys Ther 2017;47(7):472-480. Epub 16 Jun 2017. doi:10.2519/jospt.2017.7081.

  6. Multiple myeloma patients in long-term complete response after autologous stem cell transplantation express a particular immune signature with potential prognostic implication.

    Science.gov (United States)

    Arteche-López, A; Kreutzman, A; Alegre, A; Sanz Martín, P; Aguado, B; González-Pardo, M; Espiño, M; Villar, L M; García Belmonte, D; de la Cámara, R; Muñoz-Calleja, C

    2017-06-01

    The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4 + T-cells was lower in patients, whereas an increment in the percentage of CD4 + and CD8 + effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naïve cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

  7. Long-Term Collections

    CERN Multimedia

    Staff Association

    2016-01-01

    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  8. Long-Term Collection

    CERN Multimedia

    Staff Association

    2016-01-01

    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  9. Collectes à long terme

    CERN Multimedia

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  10. Jumping combined exercise programs reduce fall risk and improve balance and life quality of elderly people who live in a long-term care facility.

    Science.gov (United States)

    Cakar, E; Dincer, U; Kiralp, M Z; Cakar, D B; Durmus, O; Kilac, H; Soydan, F C; Sevinc, S; Alper, C

    2010-03-01

    The objective of this study was to determine whether regular combined exercise program, which consists strength, stretching and aerobic exercises and additional jumping training, improve balance, fall risk, quality of life and depression status of older people living in a residential care. A total of 168 residents who live in a long term care facility were screened. The trial began with 78 eligible participants and they were randomly grouped as combined exercises program (COM) group that includes stretching, strength and aerobic exercises, and COM plus jumping (COMpJ) group. 66 of the participants finished the trial. The groups were convened three times a week for six weeks. Each group had a warm-up, effective training and a cooling down periods. The total exercising time was no longer than 45 minutes in each group. Berg balance test and Biodex Balance System for the assessment of the dynamic balance and fall risk, short form 36 (SF 36) for the health related quality of life and Geriatric Depression Scale (GDS) for evaluation of the depression status were used. The balance improvement and fall risk reduction were observed in both of the groups at the end of the trial; however, the improvements were statistically better in jumping combined group. Also health related quality of life improved in both groups. Regular group exercise in a long term care facility have several beneficial effects on the elderly residents in regard to balance improvement, fall risk reduction and quality of life. The addition of jumping to strength, stretching and aerobic exercises provides important contributions to balance improvement and fall risk reduction.

  11. The long-term dynamics of mortality benefits from improved water and sanitation in less developed countries.

    Science.gov (United States)

    Jeuland, Marc A; Fuente, David E; Ozdemir, Semra; Allaire, Maura C; Whittington, Dale

    2013-01-01

    The problem of inadequate access to water, sanitation and hygiene (WASH) in less-developed nations has received much attention over the last several decades (most recently in the Millennium Development Goals), largely because diseases associated with such conditions contribute substantially to mortality in poor countries. We present country-level projections for WASH coverage and for WASH-related mortality in developing regions over a long time horizon (1975-2050) and provide dynamic estimates of the economic value of potential reductions in this WASH-related mortality, which go beyond the static results found in previous work. Over the historical period leading up to the present, our analysis shows steady and substantial improvements in WASH coverage and declining mortality rates across many developing regions, namely East Asia and the Pacific, Latin America and the Caribbean, Eastern Europe and the Middle East. The economic value of potential health gains from eliminating mortality attributable to poor water and sanitation has decreased substantially, and in the future will therefore be modest in these regions. Where WASH-related deaths remain high (in parts of South Asia and much of Sub-Saharan Africa), if current trends continue, it will be several decades before economic development and investments in improved water and sanitation will result in the capture of these economic benefits. The fact that health losses will likely remain high in these two regions over the medium term suggests that accelerated efforts are needed to improve access to water and sanitation, though the costs and benefits of such efforts in specific locations should be carefully assessed.

  12. The long-term dynamics of mortality benefits from improved water and sanitation in less developed countries.

    Directory of Open Access Journals (Sweden)

    Marc A Jeuland

    Full Text Available The problem of inadequate access to water, sanitation and hygiene (WASH in less-developed nations has received much attention over the last several decades (most recently in the Millennium Development Goals, largely because diseases associated with such conditions contribute substantially to mortality in poor countries. We present country-level projections for WASH coverage and for WASH-related mortality in developing regions over a long time horizon (1975-2050 and provide dynamic estimates of the economic value of potential reductions in this WASH-related mortality, which go beyond the static results found in previous work. Over the historical period leading up to the present, our analysis shows steady and substantial improvements in WASH coverage and declining mortality rates across many developing regions, namely East Asia and the Pacific, Latin America and the Caribbean, Eastern Europe and the Middle East. The economic value of potential health gains from eliminating mortality attributable to poor water and sanitation has decreased substantially, and in the future will therefore be modest in these regions. Where WASH-related deaths remain high (in parts of South Asia and much of Sub-Saharan Africa, if current trends continue, it will be several decades before economic development and investments in improved water and sanitation will result in the capture of these economic benefits. The fact that health losses will likely remain high in these two regions over the medium term suggests that accelerated efforts are needed to improve access to water and sanitation, though the costs and benefits of such efforts in specific locations should be carefully assessed.

  13. The anti-inflammatory drug carprofen improves long-term outcome and induces gliogenesis after traumatic brain injury.

    Science.gov (United States)

    Thau-Zuchman, Orli; Shohami, Esther; Alexandrovich, Alexander G; Trembovler, Victoria; Leker, Ronen R

    2012-01-20

    Traumatic brain injury (TBI) initiates acute and chronic inflammatory processes involving cyclooxygenase-2 (COX-2), which may have detrimental effects on outcome and especially on brain regeneration. Therefore we aimed to study whether carprofen, a COX-2 inhibitor, would improve outcome and increase neurogenesis after TBI. TBI was induced in Sabra mice that were then treated with vehicle or carprofen for 7 days. Functional outcome was evaluated with the Neurological Severity Score (NSS).Cytokine levels were assessed 4 h post-TBI and water content was measured 24 h post TBI. Mice were given BrdU to label newborn cells for 10 days. The animals were killed 90 days post-TBI and the lesion size as well as newborn cell fate were assessed. Carprofen significantly reduced lesion size (p=0.002), decreased water content in the lesioned cortex (p=0.03), reduced the number of microglia in the lesioned cortex (pCarprofen led to significantly larger improvements in functional outcome (p≤0.008) which were durable over 90 days. Carprofen also induced a threefold increase in the proliferation of new cells in the peri-lesion area (p≤0.002), but newborn cells differentiated mainly into glia in both groups. Carprofen is neuroprotective and induces cell proliferation and gliogenesis after TBI. Treatment with carprofen is consistently associated with better functional outcome. Our results imply that anti-inflammatory drugs may represent novel therapeutic options for TBI.

  14. Single-Staged Improved Tubularized Preputial/Penile Skin Flap Urethroplasty for Obliterated Anterior Urethral Stricture: Long-Term Results.

    Science.gov (United States)

    Xue, Jing-Dong; Xie, Hong; Fu, Qiang; Feng, Chao; Guo, Hui; Xu, Yue-Min

    2016-01-01

    To present an improved tubularized flap (ITF) technique and report the outcome of single-stage urethroplasty using preputial/penile skin flaps (PSFs) for the treatment of obliterative anterior urethral strictures (AUSs). From January 2000 to June 2012, 42 cases of obliterative AUS (3-14 cm, mean 6.38 cm) with urethral plate unsalvageable were treated using PSF-ITF urethroplasty including longitudinal skin flap, circular island flap, L-flap, Q-flap. Patients were divided into 3 groups: pendulous urethral stricture (Group A), bulbar urethral stricture (Group B) and panurethral strictures (Group C). Patients were followed up by uroflowmetry, urethrography and ureteroscope when necessary. The mean follow-up in these patients was 65 months (range 36 months-15 years). The primary success rates at 3-year follow-up were 75, 75 and 60% for Groups A, B and C, respectively. The overall success rates were 85, 83 and 70% with the remedial measure of a single visual internal urethrotomy at 3-year follow-up. A total 60% of the patients in the study completed more than 5 years of follow-up with no additional recurrence. Improved tubularized preputial/PSF urethroplasty with relatively high overall satisfaction is a novel technique for treatment of AUS when there is inadequate urethral plate or obliterative defects. © 2016 S. Karger AG, Basel.

  15. Understanding the inter-relationship between improved glycaemic control, hypoglycaemia and weight change within a long-term economic model.

    Science.gov (United States)

    McEwan, P; Evans, M; Kan, H; Bergenheim, K

    2010-05-01

    Current guidelines for the management of type 2 diabetes advocate the attainment of sustained near normal glycaemia levels. Metformin is widely accepted as the treatment of choice for the initiation of pharmacotherapy; however, secondary failure of oral monotherapy occurs in 60% of patients resulting in the need for multiple pharmacotherapies. Therapy-related consequences of treatment, such as weight gain and hypoglycaemia impact on the cost-effectiveness profile of various agents. We therefore sought to ascertain the respective contribution of hypoglycaemia, weight change and improved blood glucose control on second-line therapy options added to metformin. This study uses a simulation model designed to evaluate the cost utility of new therapies in a population of patients with type 2 diabetes mellitus. Standard model outputs include incidence of micro- and macrovascular complications and diabetes-specific and all-cause mortality. The mean discounted quality-adjusted life year (QALY) predicted by the model was 12.31 years. Reducing Glycosylated haemoglobin (HbA1c) by 1% gave a predicted gain of 0.413 QALYs per patient. A 3-kg weight loss and 30% reduction in hypoglycaemia frequency produced a combined QALY gain of 0.355, whereas the reverse gave a QALY decrement of 0.356. The results of this analysis quantify the QALY decrement that may result from adverse therapy effects. The beneficial effects of improved glycaemic control on QALYs may be offset by characteristic treatment-specific adverse effects, such as weight gain and hypoglycaemia frequency.

  16. Improvement in the long term creep rupture strength of SUS 316 steel for fast breeder reactors by nitrogen addition

    International Nuclear Information System (INIS)

    Nakazawa, Takanori; Abo, Hideo; Tanino, Mitsuru; Komatsu, Hazime; Tashimo, Masanori; Nishida, Takashi.

    1989-01-01

    Improvement of creep fatigue property of structural materials for fast breeder reactors. In order to improve the resistance to creep fatigue of SUS 316 steels, the effects of nitrogen, carbon, and molybdenum on creep properties have been investigated, under the concept that creep fatigue endurance is correspond to creep rupture ductility. Creep rupture tests and slow strain rate tensile tests were conducted at 550degC and extensive microstructural works were performed. The strengthening by nitrogen is much greater than carbon. Moreover, while carbon reduces rupture ductility, nitrogen does not change it. The addition of carbon results in coarse carbide formation on grain boundaries during creep, but with nitrogen very fine Fe 2 Mo particles precipitate on grain boundaries. The difference between the effects of nitrogen and carbon on creep properties is arise from the different morphology of precipitation. Strengthening by molybdenum brings about a slight decrease in rupture ductility. On the basis of these results, 0.01%C-0.07%N-11%Ni-16.5%Cr-2%Mo steel is selected as a promising material for fast breeder reactors. This steel has higher rupture ductility and strength than SUS 316 steel. It is also confirmed that this steel has a higher resistance to creep fatigue. (author)

  17. Characterization of an acute molecular marker of nongenotoxic rodent hepatocarcinogenesis by gene expression profiling in a long term clofibric acid study.

    Science.gov (United States)

    Michel, Cécile; Roberts, Ruth A; Desdouets, Chantal; Isaacs, Kevin R; Boitier, Eric

    2005-04-01

    Evaluation of the nongenotoxic potential early during the development of a drug presents a major challenge. Recently, two genes were identified as potential molecular markers of rodent hepatic carcinogenesis: transforming growth factor-beta stimulated clone 22 (TSC-22) and NAD(P)H cytochrome P450 oxidoreductase (CYP-R) (1). They were identified after comparing the gene expression profiles obtained from the livers of Sprague-Dawley rats treated with different genotoxic and nongenotoxic compounds in a 5 day repeat dose in vivo study. To assess the potential of these two genes as acute markers of carcinogenesis, we investigated their modulation during a long-term nongenotoxic study in the rat using a classic initiation-promotion regime. Clofibric acid (CLO), which belongs to the broad class of chemicals known as peroxisome proliferators, was used as a nongenotoxic hepatocarcinogen. Male F344 rats were given a single nonnecrogenic injection of diethylnitrosamine (0 or 30 mg/kg) and fed a diet containing none or 5000 ppm CLO for up to 20 months. Necropsies of five rats per groups were performed at 18, 46, 102, 264, 377, 447 (control, DEN, and DEN + CLO rats), 524, and 608 days (for the CLO and control rats). Gross macroscopic and microscopic evaluation and gene expression profiling (on Affymetrix microarrays) were performed in peritumoral and tumoral liver tissues. Bioanalysis of the liver gene expression data revealed that TSC-22 was strongly down-regulated early in the study. Its underexpression was maintained throughout the study but disappeared upon CLO withdrawal. These modulations were confirmed by real-time polymerase chain reaction. However, CYP-R gene expression was not significantly altered in our study. Taken together, our results showed that TSC-22, but not CYP-R, has the potential to be an acute early molecular marker for nongenotoxic hepatocarcinogenesis in rodents.

  18. Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

    Science.gov (United States)

    Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

    2015-07-01

    Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

  19. Long term storage in liquid nitrogen leads to only minor phenotypic and gene expression changes in the mammary carcinoma model cell line BT474.

    Science.gov (United States)

    Fazekas, Judit; Grunt, Thomas W; Jensen-Jarolim, Erika; Singer, Josef

    2017-05-23

    Cancer cell lines are indispensible surrogate models in cancer research, as they can be used off-the-shelf, expanded to the desired extent, easily modified and exchanged between research groups for affirmation, reproduction or follow-up experiments.As malignant cells are prone to genomic instability, phenotypical changes may occur after certain passages in culture. Thus, cell lines have to be regularly authenticated to ensure data quality. In between experiments these cell lines are often stored in liquid nitrogen for extended time periods.Although freezing of cells is a necessary evil, little research is performed on how long-term storage affects cancer cell lines. Therefore, this study investigated the effects of a 28-year long liquid nitrogen storage period on BT474 cells with regard to phenotypical changes, differences in cell-surface receptor expression as well as cytokine and gene expressional variations. Two batches of BT474 cells, one frozen in 1986, the other directly purchased from ATCC were investigated by light microscopy, cell growth analysis, flow cytometry and cytokine as well as whole-transcriptome expression profiling. The cell lines were morphologically indifferent and showed similar growth rates and similar cell-surface receptor expression. Transcriptome analysis revealed significant differences in only 26 of 40,716 investigated RefSeq transcripts with 4 of them being up-regulated and 22 down-regulated. This study demonstrates that even after very long periods of storage in liquid nitrogen, cancer cell lines display only minimal changes in their gene expression profiles. However, also such minor changes should be carefully assessed before continuation of experiments, especially if phenotypic alterations can be additionally observed.

  20. Reassessment of Ambulatory Blood Pressure Improves Renal Risk Stratification in Nondialysis Chronic Kidney Disease: Long-Term Cohort Study.

    Science.gov (United States)

    Minutolo, Roberto; Gabbai, Francis B; Chiodini, Paolo; Garofalo, Carlo; Stanzione, Giovanna; Liberti, Maria Elena; Pacilio, Mario; Borrelli, Silvio; Provenzano, Michele; Conte, Giuseppe; De Nicola, Luca

    2015-09-01

    In nondialysis chronic kidney disease, ambulatory blood pressure (ABP) performs better than clinic BP in predicting outcome, but whether repeated assessment of ABP further refines prognosis remains ill-defined. We recruited 182 consecutive hypertensive patients with nondialysis chronic kidney disease who underwent 2 ABPs 12 months apart to evaluate the enhancement in risk stratification provided by a second ABP obtained 1 year after baseline on the risk (hazard ratio and 95% confidence interval) of composite renal end point (death, chronic dialysis, and estimated glomerular filtration rate decline ≥40%). The difference in daytime and nighttime systolic BP between the 2 ABPs (daytime and nighttime bias) was added to a survival model including baseline ABP. Net reclassification improvement was also calculated. Age was 65.6±13.4 years; 36% had diabetes mellitus and 36% had previous cardiovascular event; estimated glomerular filtration rate was 42.2±19.6 mL/min per 1.73 m(2), and clinic BP was 145±18/80±11 mm Hg. Baseline ABP (daytime, 131±16/75±10 and nighttime, 122±18/66±10 mm Hg) and daytime/nighttime BP goals (58.2% and 43.4%) did not change at month 12. Besides baseline ABP values, bias for daytime and nighttime systolic BP linearly associated with renal outcome (1.12, 1.04-1.21 and 1.18, 1.08-1.29 for every 5-mm Hg increase, respectively). Classification of patients at risk improved when considering nighttime systolic level at second ABP (net reclassification improvement, 0.224; 95% confidence interval, 0.005-0.435). Patients with first and second ABPs above target showed greater renal risk (2.15, 1.29-3.59 and 1.71, 1.07-2.72, for daytime and nighttime, respectively). In nondialysis chronic kidney disease, reassessment of ABP at 1 year further refines renal prognosis; such reassessment should specifically be considered in patients with uncontrolled BP at baseline. © 2015 American Heart Association, Inc.

  1. Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice

    International Nuclear Information System (INIS)

    Kramer, M. Gabriela; Masner, Martín; Casales, Erkuden; Moreno, María; Smerdou, Cristian; Chabalgoity, José A.

    2015-01-01

    Metastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer. 2×10 8 particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×10 7 units of an aroC − Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay. SFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90 % of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor

  2. Improving the Long-Term Stability of Perovskite Solar Cells with a Porous Al 2 O 3 Buffer Layer

    KAUST Repository

    Guarnera, Simone; Abate, Antonio; Zhang, Wei; Foster, Jamie M.; Richardson, Giles; Petrozza, Annamaria; Snaith, Henry J.

    2015-01-01

    © 2015 American Chemical Society. Hybrid perovskites represent a new paradigm for photovoltaics, which have the potential to overcome the performance limits of current technologies and achieve low cost and high versatility. However, an efficiency drop is often observed within the first few hundred hours of device operation, which could become an important issue. Here, we demonstrate that the electrode's metal migrating through the hole transporting material (HTM) layer and eventually contacting the perovskite is in part responsible for this early device degradation. We show that depositing the HTM within an insulating mesoporous "buffer layer" comprised of Al2O3 nanoparticles prevents the metal electrode migration while allowing for precise control of the HTM thickness. This enables an improvement in the solar cell fill factor and prevents degradation of the device after 350 h of operation. (Graph Presented).

  3. Improving the Long-Term Stability of Perovskite Solar Cells with a Porous Al 2 O 3 Buffer Layer

    KAUST Repository

    Guarnera, Simone

    2015-02-05

    © 2015 American Chemical Society. Hybrid perovskites represent a new paradigm for photovoltaics, which have the potential to overcome the performance limits of current technologies and achieve low cost and high versatility. However, an efficiency drop is often observed within the first few hundred hours of device operation, which could become an important issue. Here, we demonstrate that the electrode\\'s metal migrating through the hole transporting material (HTM) layer and eventually contacting the perovskite is in part responsible for this early device degradation. We show that depositing the HTM within an insulating mesoporous "buffer layer" comprised of Al2O3 nanoparticles prevents the metal electrode migration while allowing for precise control of the HTM thickness. This enables an improvement in the solar cell fill factor and prevents degradation of the device after 350 h of operation. (Graph Presented).

  4. Different surgical strategies for chronic pancreatitis significantly improve long-term outcome: a comparative single center study

    Directory of Open Access Journals (Sweden)

    Hildebrand P

    2010-08-01

    Full Text Available Abstract Objective In general, chronic pancreatitis (CP primarily requires conservative treatment. The chronic pain syndrome and complications make patients seek surgical advice, frequently after years of progression. In the past, surgical procedures involving drainage as well as resection have been employed successfully. The present study compared the different surgical strategies. Patients and Methods From March 2000 until April 2005, a total of 51 patients underwent surgical treatment for CP at the Department of surgery, University of Schleswig-Holstein, Campus Lübeck. Out of those 51 patients, 39 (76.5% were operated according to the Frey procedure, and in 12 cases (23.5% the Whipple procedure was performed. Patient data were documented prospectively throughout the duration of the hospital stay. The evaluation of the postoperative pain score was carried out retrospectively with a validated questionnaire. Results Average operating time was 240 minutes for the Frey group and 411 minutes for the Whipple group. The medium number of blood transfusions was 1 in the Frey group and 4.5 in the Whipple group. Overall morbidity was 21% in the Frey group and 42% in the Whipple group. 30-day mortality was zero for all patients. During the median follow-up period of 50 months, an improvement in pain score was observed in 93% of the patients of the Frey group and 67% of the patients treated according to the Whipple procedure. Conclusion The results show that both the Frey procedure as well as partial pancreaticoduodenectomy are capable of improving chronic pain symptoms in CP. As far as later endocrine and exocrine pancreatic insufficiency is concerned, however, the extended drainage operation according to Frey proves to be advantageous compared to the traditional resection procedure by Whipple. Accordingly, the Frey procedure provides us with an organ-preserving surgical procedure which treats the complications of CP sufficiently, thus being an

  5. Spectroscopic Evidence of the Improvement of Reactive Iron Mineral Content in Red Soil by Long-Term Application of Swine Manure.

    Directory of Open Access Journals (Sweden)

    Chichao Huang

    Full Text Available Mineral elements in soil solutions are thought to be the precursor of the formation of reactive minerals, which play an important role in global carbon (C cycling. However, information regarding the regulation of mineral elements release in soil is scarce. Here, we examined the long-term (i.e., 23 yrs effects of fertilisation practices on Fe minerals in a red soil in Southern China. The results from chemical analysis and Fourier-transform infrared spectroscopy showed that long-term swine manure (M treatment released greater amounts of minerals into soil solutions than chemical fertilisers (NPK treatment, and Fe played a dominant role in the preservation of dissolved organic C. Furthermore, Fe K-edge X-ray absorption near-edge fine structure spectroscopy demonstrated that reactive Fe minerals were mainly composed of less crystalline ferrihydrite in the M-treated soil and more crystalline goethite in the NPK-treated soil. In conclusion, this study reported spectroscopic evidence of the improvement of reactive Femineral content in the M-treated soil colloids when compared to NPK-treated soil colloids.

  6. Effects of episodic future thinking on discounting: Personalized age-progressed pictures improve risky long-term health decisions.

    Science.gov (United States)

    Kaplan, Brent A; Reed, Derek D; Jarmolowicz, David P

    2016-03-01

    Many everyday choices are associated with both delayed and probabilistic outcomes. The temporal attention hypothesis suggests that individuals' decision making can be improved by focusing attention on temporally distal events and implies that environmental manipulations that bring temporally distal outcomes into focus may alter an individual's degree of discounting. One such manipulation, episodic future thinking, has shown to lower discount rates; however, several questions remain about the applicability of episodic future thinking to domains other than delay discounting. The present experiments examine the effects of a modified episodic-future-thinking procedure in which participants viewed age-progressed computer-generated images of themselves and answered questions related to their future, on probability discounting in the context of both a delayed health gain and loss. Results indicate that modified episodic future thinking effectively altered individuals' degree of discounting in the predicted directions and demonstrate the applicability of episodic future thinking to decision making of socially significant outcomes. © 2015 Society for the Experimental Analysis of Behavior.

  7. Improved Housing Accessibility for Older People in Sweden and Germany: Short Term Costs and Long-Term Gains.

    Science.gov (United States)

    Slaug, Björn; Chiatti, Carlos; Oswald, Frank; Kaspar, Roman; Schmidt, Steven M

    2017-08-26

    The physical housing environment is important to facilitate activities of daily living (ADL) for older people. A hindering environment may lead to ADL dependence and thus increase the need for home services, which is individually restricting and a growing societal burden. This study presents simulations of policy changes with regard to housing accessibility that estimates the potential impact specifically on instrumental activities of daily living (I-ADL), usage of home services, and related costs. The models integrate empirical data to test the hypothesis that a policy providing funding to remove the five most severe environmental barriers in the homes of older people who are at risk of developing dependence in I-ADL, can maintain independence and reduce the need for home services. In addition to official statistics from state agencies in Sweden and Germany, we utilized published results from the ENABLE-AGE and other scientific studies to generate the simulations. The simulations predicted that new policies that remove potentially hindering housing features would improve I-ADL performance among older people and reduce the need for home services. Our findings suggest that a policy change can contribute to positive effects with regard to I-ADL independence among older people and to a reduction of societal burden.

  8. Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Abbuehl, Jean-Paul; Tatarova, Zuzana; Held, Werner; Huelsken, Joerg

    2017-08-03

    Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E + (CD73) + ENG - (CD105) - LY6A + (SCA1) + BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats

    Directory of Open Access Journals (Sweden)

    Miklos Szokol

    2017-10-01

    Full Text Available The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH, in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT. Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF, fractional shortening (FS, isovolumetric relaxation time (IVRT, mitral annular plane systolic excursion (MAPSE, and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status.

  10. FAIR principles and the IEDB: short-term improvements and a long-term vision of OBO-foundry mediated machine-actionable interoperability

    Science.gov (United States)

    Vita, Randi; Overton, James A; Mungall, Christopher J; Sette, Alessandro

    2018-01-01

    Abstract The Immune Epitope Database (IEDB), at www.iedb.org, has the mission to make published experimental data relating to the recognition of immune epitopes easily available to the scientific public. By presenting curated data in a searchable database, we have liberated it from the tables and figures of journal articles, making it more accessible and usable by immunologists. Recently, the principles of Findability, Accessibility, Interoperability and Reusability have been formulated as goals that data repositories should meet to enhance the usefulness of their data holdings. We here examine how the IEDB complies with these principles and identify broad areas of success, but also areas for improvement. We describe short-term improvements to the IEDB that are being implemented now, as well as a long-term vision of true ‘machine-actionable interoperability’, which we believe will require community agreement on standardization of knowledge representation that can be built on top of the shared use of ontologies. PMID:29688354

  11. Randomised clinical trial: enteral nutrition does not improve the long-term outcome of alcoholic cirrhotic patients with jaundice.

    Science.gov (United States)

    Dupont, B; Dao, T; Joubert, C; Dupont-Lucas, C; Gloro, R; Nguyen-Khac, E; Beaujard, E; Mathurin, P; Vastel, E; Musikas, M; Ollivier, I; Piquet, M-A

    2012-05-01

    Malnutrition and jaundice are independent prognostic factors in cirrhosis. To assess the impact of enteral nutrition on the survival of alcoholic cirrhotic patients with jaundice but without acute alcoholic hepatitis. The study was a multicentre prospective randomised controlled trial comparing effects of enteral nutrition vs. a symptomatic support in patients with alcoholic cirrhosis and jaundice (bilirubin ≥51 µmol/L) but without severe acute alcoholic hepatitis. A total of 99 patients were randomised to receive either the conventional symptomatic treatment (55 patients) or the symptomatic support associated with 35 kcal/Kg/day of enteral nutrition during 4 weeks followed by an oral nutritional support during 2 months (44 patients). Randomisation was stratified on nutritional status. One-year survival curves were compared using the Kaplan-Meier method and Logrank test. Populations in both arms were similar. One-year survival was similar in the overall population (27/44 patients (61.4%) in the enteral nutrition arm vs. 36/55 (65.5%) in the control arm; Logrank P = 0.60) and in the subgroup suffering from malnutrition [18/29 patients (62.1%) in the enteral nutrition arm vs. 20/32 (62.5%) in the control arm; Logrank P = 0.99]. There was no statistical difference for bilirubin, prothrombin rate, Child-Pugh score, albumin or nutritional assessment. Complications during treatment (bleeding, encephalopathy, infection) occurred in 23% of patients in the enteral nutrition group (10/44) vs. 16% (9/55) of the control patients (P = 0.59). Enteral nutrition does not improve the survival and hepatic or nutritional parameters of cirrhotic patients with jaundice. © 2012 Blackwell Publishing Ltd.

  12. Improving the long-term stability of PBDTTPD polymer solar cells through material purification aimed at removing organic impurities

    KAUST Repository

    Mateker, William R.; Douglas, Jessica D.; Cabanetos, Clement; Sachs-Quintana, I. T.; Bartelt, Jonathan A.; Hoke, Eric T.; El Labban, Abdulrahman; Beaujuge, Pierre; Frechet, Jean; McGehee, Michael D.

    2013-01-01

    While bulk heterojunction (BHJ) solar cells fabricated from high M n PBDTTPD achieve power conversion efficiencies (PCE) as high as 7.3%, the short-circuit current density (JSC) of these devices can drop by 20% after seven days of storage in the dark and under inert conditions. This degradation is characterized by the appearance of S-shape features in the reverse bias region of current-voltage (J-V) curves that increase in amplitude over time. Conversely, BHJ solar cells fabricated from low Mn PBDTTPD do not develop S-shaped J-V curves. However, S-shapes identical to those observed in high Mn PBDTTPD solar cells can be induced in low M n devices through intentional contamination with the TPD monomer. Furthermore, when high Mn PBDTTPD is purified via size exclusion chromatography (SEC) to reduce the content of low molecular weight species, the JSC of polymer devices is significantly more stable over time. After 111 days of storage in the dark under inert conditions, the J-V curves do not develop S-shapes and the JSC degrades by only 6%. The S-shape degradation feature, symptomatic of low device lifetimes, appears to be linked to the presence of low molecular weight contaminants, which may be trapped within samples of high Mn polymer that have not been purified by SEC. Although these impurities do not affect initial device PCE, they significantly reduce device lifetime, and solar cell stability is improved by increasing the purity of the polymer materials. © 2013 The Royal Society of Chemistry.

  13. Facial primer provides immediate and long-term improvements in mild-to-moderate facial hyperpigmentation and fine lines associated with photoaging

    Directory of Open Access Journals (Sweden)

    Roberts WE

    2015-09-01

    Full Text Available Wendy E Roberts,1 Lily I Jiang,2 James H Herndon Jr3 1Generational and Cosmetic Dermatology, Rancho Mirage, CA, 2Thomas J Stephens and Associates, Richardson, 3Dermatology Center of Dallas, Dallas, TX, USA Background: Photoaged skin results from various environmental factors, most importantly chronic sun exposure. Dyschromia and fine lines/wrinkles are common clinical manifestations of photodamaged skin. Purpose: This single-center clinical trial was conducted to assess the efficacy and tolerability of a new multifunctional facial primer (camouflage, broad-spectrum SPF 50, and a treatment for hyperpigmentation when used by females with mild-to-moderate facial hyperpigmentation and fine lines due to photoaging over a course of 12 weeks. Patients and methods: Subjects were provided test material (Even Up-Clinical Pigment Perfector and supporting products to use on their face and neck. Products were used according to specific application instructions. Clinical grading for efficacy and tolerability assessments were performed by an expert grader at baseline, baseline (post-application primer, week 4, week 8, week 12, and week 12 (post-application primer. Standardized digital photographs were taken, and self-assessment questionnaires were conducted. Results: Twenty-eight female subjects completed the 12-week trial. The facial primer improved scores for the appearance of hyperpigmentation and other photoaging parameters immediately after the first application. The treatment also showed a progressive improvement in the clinical assessment of hyperpigmentation and other photoaging parameters over the 12-week trial. These long-term benefits can be attributed to an improvement in the underlying skin condition. The facial primer was well tolerated. Subject questionnaires showed that the product was highly rated at all visits. Conclusion: The facial primer was shown to be effective and well tolerated for immediate and long-term improvement in the appearance

  14. Long-term lifestyle intervention with optimized high-intensity interval training improves body composition, cardiometabolic risk, and exercise parameters in patients with abdominal obesity.

    Science.gov (United States)

    Gremeaux, Vincent; Drigny, Joffrey; Nigam, Anil; Juneau, Martin; Guilbeault, Valérie; Latour, Elise; Gayda, Mathieu

    2012-11-01

    The aim of this study was to study the impact of a combined long-term lifestyle and high-intensity interval training intervention on body composition, cardiometabolic risk, and exercise tolerance in overweight and obese subjects. Sixty-two overweight and obese subjects (53.3 ± 9.7 yrs; mean body mass index, 35.8 ± 5 kg/m(2)) were retrospectively identified at their entry into a 9-mo program consisting of individualized nutritional counselling, optimized high-intensity interval exercise, and resistance training two to three times a week. Anthropometric measurements, cardiometabolic risk factors, and exercise tolerance were measured at baseline and program completion. Adherence rate was 97%, and no adverse events occurred with high-intensity interval exercise training. Exercise training was associated with a weekly energy expenditure of 1582 ± 284 kcal. Clinically and statistically significant improvements were observed for body mass (-5.3 ± 5.2 kg), body mass index (-1.9 ± 1.9 kg/m(2)), waist circumference (-5.8 ± 5.4 cm), and maximal exercise capacity (+1.26 ± 0.84 metabolic equivalents) (P high-density lipoprotein ratio were also significantly improved (P body mass and waist circumference loss were baseline body mass index and resting metabolic rate; those for body mass index decrease were baseline waist circumference and triglyceride/high-density lipoprotein cholesterol ratio. A long-term lifestyle intervention with optimized high-intensity interval exercise improves body composition, cardiometabolic risk, and exercise tolerance in obese subjects. This intervention seems safe, efficient, and well tolerated and could improve adherence to exercise training in this population.

  15. Improvement of non-key traits in radiata pine breeding programme when long-term economic importance is uncertain.

    Science.gov (United States)

    Li, Yongjun; Dungey, Heidi; Yanchuk, Alvin; Apiolaza, Luis A

    2017-01-01

    Diameter at breast height (DBH), wood density (DEN) and predicted modulus of elasticity (PME) are considered as 'key traits' (KT) in the improvement in radiata pine breeding programmes in New Zealand. Any other traits which are also of interest to radiata pine breeders and forest growers are called 'non-key traits' (NKTs). External resin bleeding (ERB), internal checking (IC), number of heartwood rings (NHR) are three such non-key traits which affect wood quality of radiata pine timber. Economic importance of the KTs and NKTs is hard to define in radiata pine breeding programmes due to long rotation period. Desired-gain index (DGIs) and robust selection were proposed to incorporate NKTs into radiata pine breeding programme in order to deal with the uncertainty of economic importance. Four desired-gain indices A-D were proposed in this study. The desired-gain index A (DGI-A) emphasized growth and led to small decrease in ERB and small increase in IC and NHR. The expected genetic gains of all traits in the desired-gain index B (DGI-B) were in the favourable directions (positive genetic gains in the key traits and negative genetic gains in the non-key traits). The desired-gain index C (DGI-C) placed emphasis on wood density, leading to favourable genetic gain in the NKTs but reduced genetic gains for DBH and PME. The desired-gain index D (DGI-D) exerted a bit more emphasis on the non-key traits, leading large favourable reduction in the non-key traits and lower increase in the key traits compared with the other DGIs. When selecting both the key traits and the non-key traits, the average EBVs of six traits were all in the same directions as the expected genetic gains except for DBH in the DGI-D. When the key traits were measured and selected, internal checking always had a negative (favourable) genetic gain but ERB and NHR had unfavourable genetic gain in the most of time. After removing some individuals with high sensitivity to the change of economic weights, robust

  16. Improvement of non-key traits in radiata pine breeding programme when long-term economic importance is uncertain.

    Directory of Open Access Journals (Sweden)

    Yongjun Li

    Full Text Available Diameter at breast height (DBH, wood density (DEN and predicted modulus of elasticity (PME are considered as 'key traits' (KT in the improvement in radiata pine breeding programmes in New Zealand. Any other traits which are also of interest to radiata pine breeders and forest growers are called 'non-key traits' (NKTs. External resin bleeding (ERB, internal checking (IC, number of heartwood rings (NHR are three such non-key traits which affect wood quality of radiata pine timber. Economic importance of the KTs and NKTs is hard to define in radiata pine breeding programmes due to long rotation period. Desired-gain index (DGIs and robust selection were proposed to incorporate NKTs into radiata pine breeding programme in order to deal with the uncertainty of economic importance. Four desired-gain indices A-D were proposed in this study. The desired-gain index A (DGI-A emphasized growth and led to small decrease in ERB and small increase in IC and NHR. The expected genetic gains of all traits in the desired-gain index B (DGI-B were in the favourable directions (positive genetic gains in the key traits and negative genetic gains in the non-key traits. The desired-gain index C (DGI-C placed emphasis on wood density, leading to favourable genetic gain in the NKTs but reduced genetic gains for DBH and PME. The desired-gain index D (DGI-D exerted a bit more emphasis on the non-key traits, leading large favourable reduction in the non-key traits and lower increase in the key traits compared with the other DGIs. When selecting both the key traits and the non-key traits, the average EBVs of six traits were all in the same directions as the expected genetic gains except for DBH in the DGI-D. When the key traits were measured and selected, internal checking always had a negative (favourable genetic gain but ERB and NHR had unfavourable genetic gain in the most of time. After removing some individuals with high sensitivity to the change of economic weights

  17. Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models.

    Science.gov (United States)

    Bigagli, Elisabetta; Luceri, Cristina; Scartabelli, Tania; Dolara, Piero; Casamenti, Fiorella; Pellegrini-Giampietro, Domenico E; Giovannelli, Lisa

    2016-01-01

    Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-β deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-β-galactosidase activity, oxidative stress, γ-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 µM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement.

    Science.gov (United States)

    Naugle, Michelle M; Gore, Andrea C

    2014-01-01

    Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responds to the primary regulatory sex steroid hormone, estradiol (E2), are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons and whether this changes with aging and/or E2 treatment. We used immunofluorescence double-labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2-year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double-labeled. Additionally, many GPER-labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust co-localization of GPER in GnRH in a clinically relevant model, and they support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates.

  19. Long-term effect of early nutrition on endocrine parameters and liver and endometrial gene expression of the members of the somatotrophic axis in Hereford heifers.

    Science.gov (United States)

    Guggeri, D; Meikle, A; Carriquiry, M; De Barbieri, I; Montossi, F; Viñoles, C

    2018-04-23

    This study compared the effect of different management systems on endocrine parameters, and gene expression of members of the somatotrophic axis in the liver and endometrium of beef heifers. Twenty-two 709-days-old heifers submitted to Early Weaning (EW, n = 8), Traditional Weaning (TW, n = 7) and TW plus creep feeding (TW+CF, n = 7) were used. Animals were synchronized with two prostaglandin (PG) injections at 11-day interval (Oestrus = Day 0). Blood samples were collected daily for progesterone (P4) determination, and endometrial and liver biopsies on Days 7 and 16 for transcript determination of members of the somatotrophic axis. Progesterone concentrations were greater on Days 15 and 16 (p < .02) of the cycle in TW+CF than TW and EW heifers. On Day 7, TW+CF heifers expressed greater liver total growth hormone receptor transcripts than TW heifers (p = .05) and greater insulin-like growth factor (IGF)-binding protein 3 mRNA than both EW and TW groups (p < .05). On Days 7 and 16, TW+CF expressed more endometrial IGF1 mRNA than the other groups (p < .01). We conclude that increasing the plane of nutrition of nursing calves may have a long-term effect on the functioning of the somatotrophic axis both in the liver and in the endometrium. © 2018 Blackwell Verlag GmbH.

  20. Expression of StAR and Key Genes Regulating Cortisol Biosynthesis in Near Term Ovine Fetal Adrenocortical Cells: Effects of Long-Term Hypoxia.

    Science.gov (United States)

    Vargas, Vladimir E; Myers, Dean A; Kaushal, Kanchan M; Ducsay, Charles A

    2018-02-01

    We previously demonstrated decreased expression of key genes regulating cortisol biosynthesis in long-term hypoxic (LTH) sheep fetal adrenals compared to controls. We also showed that inhibition of the extracellular signal-regulated kinases (ERKs) with the mitogen-activated protein kinase (MEK)/ERK inhibitor UO126 limited adrenocorticotropic (ACTH)-induced cortisol production in ovine fetal adrenocortical cells (FACs), suggesting a role for ERKs in cortisol synthesis. This study was designed to determine whether the previously observed decrease in LTH cytochrome P45011A1/cytochrome P450c17 (CYP11A1/CYP17) in adrenal glands was maintained in vitro, and whether ACTH alone with or without UO126 treatment had altered the expression of CYP11A1, CYP17, and steroidogenic acute regulatory protein (StAR) in control versus LTH FACs. Ewes were maintained at high altitude (3820 m) from ∼40 days of gestation (dG). At 138 to 141 dG, fetal adrenal glands were collected from LTH (n = 5) and age-matched normoxic controls (n = 6). Fetal adrenocortical cells were challenged with ACTH (10 -8 M) with or without UO126 (10 µM) for 18 hours. Media samples were collected for cortisol analysis and messenger RNA (mRNA) for CYP11A1, CYP17, and StAR was quantified by quantitative real-time polymerase chain reaction. Cortisol was higher in the LTH versus control ( P StAR mRNA was decreased in LTH versus control ( P StAR expression.

  1. The use of data for process and quality improvement in long term care and home care: a systematic review of the literature.

    Science.gov (United States)

    Sales, Anne E; Bostrom, Anne-Marie; Bucknall, Tracey; Draper, Kellie; Fraser, Kimberly; Schalm, Corinne; Warren, Sharon

    2012-02-01

    Standardized resident or client assessments, including the Resident Assessment Instrument (RAI), have been available in long term care and home care settings (continuing care sector) in many jurisdictions for a number of years. Although using these data can make quality improvement activities more efficient and less costly, there has not been a review of the literature reporting quality improvement interventions using standardized data. To address 2 questions: (1) How have RAI and other standardized data been used in process or quality improvement activities in the continuing care sector? and (2) Has the use of RAI and similar data resulted in improvements to resident or other outcomes? Searches using a combination of keyword and controlled vocabulary term searches were conducted in MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, the Cochrane Library, and PsychINFO. ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: English language publications from database inception to October 2008 were included. Eligibility criteria included the following: (1) set in continuing care (long-term care facility or home care), (2) involved some form of intervention designed to improve quality or process of care, and (3) used standardized data in the quality or process improvement intervention. After reviewing the articles, we grouped the studies according to the type of intervention used to initiate process improvement. Four different intervention types were identified. We organized the results and discussion by these 4 intervention types. Key word searches identified 713 articles, of which we excluded 639 on abstract review because they did not meet inclusion criteria. A further 50 articles were excluded on full-text review, leaving a total of 24 articles. Of the 24 studies, 10 used a defined process improvement model, 8 used a combination of interventions (multimodal), 5 implemented new guidelines or protocols, and 1 used an education

  2. NMDA and kainate receptor expression, long-term potentiation, and neurogenesis in the hippocampus of long-lived Ames dwarf mice.

    Science.gov (United States)

    Sharma, Sunita; Darland, Diane; Lei, Saobo; Rakoczy, Sharlene; Brown-Borg, Holly M

    2012-06-01

    In the current study, we investigated changes in N-methyl D-aspartate (NMDA) and kainate receptor expression, long-term potentiation (LTP), and neurogenesis in response to neurotoxic stress in long-living Ames dwarf mice. We hypothesized that Ames dwarf mice have enhanced neurogenesis that enables retention of spatial learning and memory with age and promotes neurogenesis in response to injury. Levels of the NMDA receptors (NR)1, NR2A, NR2B, and the kainate receptor (KAR)2 were increased in Ames dwarf mice, relative to wild-type littermates. Quantitative assessment of the excitatory postsynaptic potential in Schaffer collaterals in hippocampal slices from Ames dwarf mice showed an increased response in high-frequency induced LTP over time compared with wild type. Kainic acid (KA) injection was used to promote neurotoxic stress-induced neurogenesis. KA mildly increased the number of doublecortin-positive neurons in wild-type mice, but the response was significantly enhanced in the Ames dwarf mice. Collectively, these data support our hypothesis that the enhanced learning and memory associated with the Ames dwarf mouse may be due to elevated levels of NMDA and KA receptors in hippocampus and their ability to continue producing new neurons in response to neuronal damage.

  3. The use of long term agreements to improve energy efficiency in the industrial sector: Overview of the European experiences and proposal for a common framework

    International Nuclear Information System (INIS)

    Bertoldi, P.

    1999-01-01

    In the European Union efficiency improvements in the industrial sector are regarded as a key element of Member States' strategies to meet their Kyoto target. Besides the traditional policy instruments, such as fiscal and financial aids, minimum efficiency standards, R and D and technology programs, there is an increasing interest by both public authorities and industry for voluntary approaches to improve industrial energy efficiency. In the European context the term voluntary approach is often used to describe a wide range of industry actions including, inter alia: industry covenants, negotiated agreements, long term agreements, self regulations, codes of conduct, benchmarking and monitoring schemes. These voluntary approaches differ in relation to their form, legal status, provisions and enforceability. The paper provides an up-to-date overview of the present status of the different voluntary approaches for the industrial sector in several Member States (the Netherlands, Sweden, Germany, Denmark, Finland, Ireland, and the United Kingdom). The paper will focus on the particular type of voluntary approach implemented in the Netherlands and commonly called Long Term Agreements (LTA). The paper analyses the opportunities and advantages for creating a common EU framework for the conclusion and implementation of LTAs, based on the successful Dutch model. In doing so, the paper intends also to contribute to the approximation of the LTA's essential elements throughout the Community in order to reduce possible distortions of the internal market and of the competitive position of national industries, thus enlarging the acceptability of this instrument by public authorities and industry. For some industrial sectors, which are quite homogeneous throughout the Community and represent a limited number of companies, the paper analyses the advantages of having European LTAs and recommends their implementation. The paper presents the achievable results at EU level in terms of

  4. The NHV rehabilitation services program improves long-term physical functioning in survivors of the 2008 Sichuan earthquake: a longitudinal quasi experiment.

    Directory of Open Access Journals (Sweden)

    Xia Zhang

    Full Text Available BACKGROUND: Long-term disability following natural disasters significantly burdens survivors and the impacted society. Nevertheless, medical rehabilitation programming has been historically neglected in disaster relief planning. 'NHV' is a rehabilitation services program comprised of non-governmental organizations (NGOs (N, local health departments (H, and professional rehabilitation volunteers (V which aims to improve long-term physical functioning in survivors of the 2008 Sichuan earthquake. We aimed to evaluate the effectiveness of the NHV program. METHODS/FINDINGS: 510 of 591 enrolled earthquake survivors participated in this longitudinal quasi-experimental study (86.3%. The early intervention group (NHV-E consisted of 298 survivors who received institutional-based rehabilitation (IBR followed by community-based rehabilitation (CBR; the late intervention group (NHV-L was comprised of 101 survivors who began rehabilitation one year later. The control group of 111 earthquake survivors did not receive IBR/CBR. Physical functioning was assessed using the Barthel Index (BI. Data were analyzed with a mixed-effects Tobit regression model. Physical functioning was significantly increased in the NHV-E and NHV-L groups at follow-up but not in the control group after adjustment for gender, age, type of injury, and time to measurement. We found significant effects of both NHV (11.14, 95% CI 9.0-13.3 and sponaneaous recovery (5.03; 95% CI 1.73-8.34. The effect of NHV-E (11.3, 95% CI 9.0-13.7 was marginally greater than that of NHV-L (10.7, 95% CI 7.9-13.6. It could, however, not be determined whether specific IBR or CBR program components were effective since individual component exposures were not evaluated. CONCLUSION: Our analysis shows that the NHV improved the long-term physical functioning of Sichuan earthquake survivors with disabling injuries. The comprehensive rehabilitation program benefitted the individual and society, rehabilitation services

  5. Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with improved long-term survival.

    Science.gov (United States)

    Ali, Ayyaz; Patel, Amit; Ali, Ziad; Abu-Omar, Yasir; Saeed, Amber; Athanasiou, Thanos; Pepper, John

    2011-08-01

    Aortic valve replacement in patients with aortic stenosis is usually followed by regression of left ventricular hypertrophy. More complete resolution of left ventricular hypertrophy is suggested to be associated with superior clinical outcomes; however, its translational impact on long-term survival after aortic valve replacement has not been investigated. Demographic, operative, and clinical data were obtained retrospectively through case note review. Transthoracic echocardiography was used to measure left ventricular mass preoperatively and at annual follow-up visits. Patients were classified according to their reduction in left ventricular mass at 1 year after the operation: group 1, less than 25 g; group 2, 25 to 150 g; and group 3, more than 150 g. Kaplan-Meier and multivariable Cox regression were used. A total of 147 patients were discharged from the hospital after aortic valve replacement for aortic stenosis between 1991 and 2001. Preoperative left ventricular mass was 279 ± 98 g in group 1 (n = 47), 347 ± 104 g in group 2 (n = 62), and 491 ± 183 g in group 3 (n = 38) (P regression such as ischemic heart disease or hypertension, valve type, or valve size used. Ten-year actuarial survival was not statistically different in patients with enhanced left ventricular mass regression when compared with the log-rank test (group 1, 51% ± 9%; group 2, 54% ± 8%; and group 3, 72% ± 10%) (P = .26). After adjustment, left ventricular mass reduction of more than 150 g was demonstrated as an independent predictor of improved long-term survival on multivariate analysis (P = .02). Our study is the first to suggest that enhanced postoperative left ventricular mass regression, specifically in patients undergoing aortic valve replacement for aortic stenosis, may be associated with improved long-term survival. In view of these findings, strategies purported to be associated with superior left ventricular mass regression should be considered when undertaking

  6. The abilities of improved schizophrenia patients to work and live independently in the community: a 10-year long-term outcome study from Mumbai, India

    Directory of Open Access Journals (Sweden)

    Thakar Meghana

    2009-10-01

    Full Text Available Abstract Background The outcome of first episode schizophrenia has several determinants. Socioecological factors, particularly living conditions, migration, community and culture, not only affect the level of risk but also the outcome. Mega cities around the world show a unique socioecological condition that has several challenges for mental health. The present study reports on the long-term status of patients with schizophrenia in such a mega city: Mumbai, India. Aim This study aims to reveal the long-term outcome of patients suffering from schizophrenia with special reference to clinical symptoms and social functioning. Methods The cohort for this study was drawn from a 10-year follow-up of first episode schizophrenia. Patients having completed 10 years of consistent treatment after first hospitalisation were assessed on psychopathological and recovery criteria. Clinical as well as social parameters of recovery were evaluated. Descriptive statistics with 95% confidence intervals are provided. Results Of 200 patients recruited at the beginning of this study, 122 patients (61% were present in the city of Mumbai at the end of 10-year follow-up study period. Among 122 available patients, 101 patients (50.5% were included in the assessment at the end of 10-year follow-up study period, 6 patients (3.0% were excluded from the study due to changed diagnosis, and 15 patients (7.5% were excluded due to admission into long-term care facilities. This indicates that 107 out of 122 available patients (87.7% were living in the community with their families. Out of 101 (50.5% patients assessed at the end of 10 years, 61 patients (30.5% showed improved recovery on the Clinical Global Impression Scale, 40 patients (20% revealed no improvement in the recovery, 43 patients (72.9% were able to live independently, and 24 patients (40% were able to find employment. Conclusion With 10 years of treatment, the recovery rate among schizophrenia patients in Mumbai was 30

  7. The abilities of improved schizophrenia patients to work and live independently in the community: a 10-year long-term outcome study from Mumbai, India.

    Science.gov (United States)

    Srivastava, Amresh Kumar; Stitt, Larry; Thakar, Meghana; Shah, Nilesh; Chinnasamy, Gurusamy

    2009-10-13

    The outcome of first episode schizophrenia has several determinants. Socioecological factors, particularly living conditions, migration, community and culture, not only affect the level of risk but also the outcome. Mega cities around the world show a unique socioecological condition that has several challenges for mental health. The present study reports on the long-term status of patients with schizophrenia in such a mega city: Mumbai, India. This study aims to reveal the long-term outcome of patients suffering from schizophrenia with special reference to clinical symptoms and social functioning. The cohort for this study was drawn from a 10-year follow-up of first episode schizophrenia. Patients having completed 10 years of consistent treatment after first hospitalisation were assessed on psychopathological and recovery criteria. Clinical as well as social parameters of recovery were evaluated. Descriptive statistics with 95% confidence intervals are provided. Of 200 patients recruited at the beginning of this study, 122 patients (61%) were present in the city of Mumbai at the end of 10-year follow-up study period. Among 122 available patients, 101 patients (50.5%) were included in the assessment at the end of 10-year follow-up study period, 6 patients (3.0%) were excluded from the study due to changed diagnosis, and 15 patients (7.5%) were excluded due to admission into long-term care facilities. This indicates that 107 out of 122 available patients (87.7%) were living in the community with their families. Out of 101 (50.5%) patients assessed at the end of 10 years, 61 patients (30.5%) showed improved recovery on the Clinical Global Impression Scale, 40 patients (20%) revealed no improvement in the recovery, 43 patients (72.9%) were able to live independently, and 24 patients (40%) were able to find employment. With 10 years of treatment, the recovery rate among schizophrenia patients in Mumbai was 30.5%. Among the patients, 87.7% of patients lived in the

  8. The NHV rehabilitation services program improves long-term physical functioning in survivors of the 2008 Sichuan earthquake: a longitudinal quasi experiment.

    Science.gov (United States)

    Zhang, Xia; Reinhardt, Jan D; Gosney, James E; Li, Jianan

    2013-01-01

    Long-term disability following natural disasters significantly burdens survivors and the impacted society. Nevertheless, medical rehabilitation programming has been historically neglected in disaster relief planning. 'NHV' is a rehabilitation services program comprised of non-governmental organizations (NGOs) (N), local health departments (H), and professional rehabilitation volunteers (V) which aims to improve long-term physical functioning in survivors of the 2008 Sichuan earthquake. We aimed to evaluate the effectiveness of the NHV program. 510 of 591 enrolled earthquake survivors participated in this longitudinal quasi-experimental study (86.3%). The early intervention group (NHV-E) consisted of 298 survivors who received institutional-based rehabilitation (IBR) followed by community-based rehabilitation (CBR); the late intervention group (NHV-L) was comprised of 101 survivors who began rehabilitation one year later. The control group of 111 earthquake survivors did not receive IBR/CBR. Physical functioning was assessed using the Barthel Index (BI). Data were analyzed with a mixed-effects Tobit regression model. Physical functioning was significantly increased in the NHV-E and NHV-L groups at follow-up but not in the control group after adjustment for gender, age, type of injury, and time to measurement. We found significant effects of both NHV (11.14, 95% CI 9.0-13.3) and sponaneaous recovery (5.03; 95% CI 1.73-8.34). The effect of NHV-E (11.3, 95% CI 9.0-13.7) was marginally greater than that of NHV-L (10.7, 95% CI 7.9-13.6). It could, however, not be determined whether specific IBR or CBR program components were effective since individual component exposures were not evaluated. Our analysis shows that the NHV improved the long-term physical functioning of Sichuan earthquake survivors with disabling injuries. The comprehensive rehabilitation program benefitted the individual and society, rehabilitation services in China, and international rehabilitation

  9. A study on making a long-term improvement in the national energy efficiency and GHG control plans by the AHP approach

    International Nuclear Information System (INIS)

    Lee, Seong Kon; Yoon, Yong Jin; Kim, Jong Wook

    2007-01-01

    Owing to the expiration of the national 10-year period plan and the establishment of an efficient energy and resource technology R and D system, the Korean government needs to make a strategic long-term national energy and resource technology R and D plan (NERP) to cope with forthcoming 10-year period. A new NERP aims to improve the energy intensity, reduce the emissions of greenhouse gas within the United Nations framework convention on climate change (UNFCCC), and contribute to the construction of an advanced economic system. We determine the priorities in technology development for the energy efficiency and greenhouse gas control plans (EGCP), which are parts of a new NERP, by using the AHP approach for the first time. We suggest a scientific procedure to determine the priorities in technology development by using AHP

  10. Intrathecal long-term gene expression by self-complementary adeno-associated virus type 1 suitable for chronic pain studies in rats

    Directory of Open Access Journals (Sweden)

    Janssen William GM

    2006-01-01

    Full Text Available Abstract Background Intrathecal (IT gene transfer is an attractive approach for targeting spinal mechanisms of nociception but the duration of gene expression achieved by reported methods is short (up to two weeks impairing their utility in the chronic pain setting. The overall goal of this study was to develop IT gene transfer yielding true long-term transgene expression defined as ≥ 3 mo following a single vector administration. We defined "IT" administration as atraumatic injection into the lumbar cerebrospinal fluid (CSF modeling a lumbar puncture. Our studies focused on recombinant adeno-associated virus (rAAV, one of the most promising vector types for clinical use. Results Conventional single stranded rAAV2 vectors performed poorly after IT delivery in rats. Pseudotyping of rAAV with capsids of serotypes 1, 3, and 5 was tested alone or in combination with a modification of the inverted terminal repeat. The former alters vector tropism and the latter allows packaging of self-complementary rAAV (sc-rAAV vectors. Combining both types of modification led to the identification of sc-rAAV2/l as a vector that performed superiorly in the IT space. IT delivery of 3 × 10e9 sc-rAAV2/l particles per animal led to stable expression of enhanced green fluorescent protein (EGFP for ≥ 3 mo detectable by Western blotting, quantitative PCR, and in a blinded study by confocal microscopy. Expression was strongest in the cauda equina and the lower sections of the spinal cord and only minimal in the forebrain. Microscopic examination of the SC fixed in situ with intact nerve roots and meninges revealed strong EGFP fluorescence in the nerve roots. Conclusion sc-rAAVl mediates stable IT transgene expression for ≥ 3 mo. Our findings support the underlying hypothesis that IT target cells for gene transfer lack the machinery for efficient conversion of the single-stranded rAAV genome into double-stranded DNA and favor uptake of serotype 1 vectors over 2

  11. Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.

    Science.gov (United States)

    Dossat, Amanda M; Jourdi, Hussam; Wright, Katherine N; Strong, Caroline E; Sarkar, Ambalika; Kabbaj, Mohamed

    2017-01-06

    In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-01-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E 2 ). With these LTEE cells and with parallel control cells cultured without E 2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E 2 -dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E 2 .

  13. Short and long-term impact of lipectomy on expression profile of hepatic anabolic genes in rats: a high fat and high cholesterol diet-induced obese model.

    Science.gov (United States)

    Ling, Bey-Leei; Chiu, Chun-Tang; Lu, Hsiu-Chin; Lin, Jin-Jin; Kuo, Chiung-Yin; Chou, Fen-Pi

    2014-01-01

    To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR) ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α) and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC) analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, Pshort term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These metabolic changes could be the results of reduced circulating adiponectin that further influences the functions of insulin and hepatic HNF4α.

  14. Introduction: Long term prediction

    International Nuclear Information System (INIS)

    Beranger, G.

    2003-01-01

    Making a decision upon the right choice of a material appropriate to a given application should be based on taking into account several parameters as follows: cost, standards, regulations, safety, recycling, chemical properties, supplying, transformation, forming, assembly, mechanical and physical properties as well as the behaviour in practical conditions. Data taken from a private communication (J.H.Davidson) are reproduced presenting the life time range of materials from a couple of minutes to half a million hours corresponding to applications from missile technology up to high-temperature nuclear reactors or steam turbines. In the case of deep storage of nuclear waste the time required is completely different from these values since we have to ensure the integrity of the storage system for several thousand years. The vitrified nuclear wastes should be stored in metallic canisters made of iron and carbon steels, stainless steels, copper and copper alloys, nickel alloys or titanium alloys. Some of these materials are passivating metals, i.e. they develop a thin protective film, 2 or 3 nm thick - the so-called passive films. These films prevent general corrosion of the metal in a large range of chemical condition of the environment. In some specific condition, localized corrosion such as the phenomenon of pitting, occurs. Consequently, it is absolutely necessary to determine these chemical condition and their stability in time to understand the behavior of a given material. In other words the corrosion system is constituted by the complex material/surface/medium. For high level nuclear wastes the main features for resolving problem are concerned with: geological disposal; deep storage in clay; waste metallic canister; backfill mixture (clay-gypsum) or concrete; long term behavior; data needed for modelling and for predicting; choice of appropriate solution among several metallic candidates. The analysis of the complex material/surface/medium is of great importance

  15. Long-Term Symbolic Learning

    National Research Council Canada - National Science Library

    Kennedy, William G; Trafton, J. G

    2007-01-01

    What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

  16. Long-term hormonal contraceptive use is associated with a reversible suppression of antral follicle count and a break from hormonal contraception may improve oocyte yield.

    Science.gov (United States)

    Letourneau, Joseph M; Cakmak, Hakan; Quinn, Molly; Sinha, Nikita; I Cedars, Marcelle; Rosen, Mitchell P

    2017-09-01

    Unlike infertility, patients presenting for fertility preservation (FP) are often using combined hormonal contraceptives (CHC). We studied whether long-term (≥6 months) CHC use is associated with reversible suppression of antral follicle count (AFC). This is a longitudinal study of FP cycles from 2012 to 2016. We studied three groups: those without CHC exposure (NO CHC), those with CHC usage with a CHC break (BREAK), and without a break (NO BREAK) prior to ovarian stimulation. We assessed ovarian reserve by AFC at initial consultation and discussed the possibility of CHC suppression of AFC. Patients chose between ovarian stimulation with no CHC break versus ovarian stimulation after a CHC break. AFC was measured serially in the BREAK group. We assessed whether AFC suppression was reversed in the BREAK group. Total oocyte yield was compared among the NO CHC, BREAK, and NO BREAK groups. T tests, ANOVA, and linear/logistic regressions were used. Seven hundred forty-three women underwent FP. Twenty-one percent (n = 154) were taking long-term CHC (≥6 months). AFC suppression was more likely with CHC use (OR 1.6, 95% CI 1.1-2.4, P = 0.011). The BREAK group (n = 79) stopped CHC for an average of 4 months. AFC improvement started at 1 month and plateaued at approximately 6- to 7-month break. The BREAK group had approximately twice as many oocytes per initial AFC as NO BREAK (2.8 ± 3.8 vs. 1.4 ± 0.9, P women present for FP on CHC, AFC may be suppressed. A CHC break of several months is associated with an increase in AFC and a potential improvement in overall egg yield.

  17. Avocado oil induces long-term alleviation of oxidative damage in kidney mitochondria from type 2 diabetic rats by improving glutathione status.

    Science.gov (United States)

    Ortiz-Avila, Omar; Figueroa-García, María Del Consuelo; García-Berumen, Claudia Isabel; Calderón-Cortés, Elizabeth; Mejía-Barajas, Jorge A; Rodriguez-Orozco, Alain R; Mejía-Zepeda, Ricardo; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2017-04-01

    Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

  18. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    International Nuclear Information System (INIS)

    Franckena, Martine; Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-01-01

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research

  19. Intensity-Modulated Radiotherapy is Associated With Improved Global Quality of Life Among Long-term Survivors of Head-and-Neck Cancer

    International Nuclear Information System (INIS)

    Chen, Allen M.; Farwell, D. Gregory; Luu, Quang; Vazquez, Esther G.; Lau, Derick H.; Purdy, James A.

    2012-01-01

    Purpose: To compare the long-term quality of life among patients treated with and without intensity-modulated radiotherapy (IMRT) for head-and-neck cancer. Methods and Materials: University of Washington Quality of Life instrument scores were reviewed for 155 patients previously treated with radiation therapy for locally advanced head-and-neck cancer. All patients were disease free and had at least 2 years of follow-up. Eighty-four patients (54%) were treated with IMRT. The remaining 71 patients (46%) were treated with three-dimensional conformal radiotherapy (3D CRT) by use of initial opposed lateral fields matched to a low anterior neck field. Results: The mean global quality of life scores were 67.5 and 80.1 for the IMRT patients at 1 and 2 years, respectively, compared with 55.4 and 57.0 for the 3D CRT patients, respectively (p < 0.001). At 1 year after the completion of radiation therapy, the proportion of patients who rated their global quality of life as “very good” or “outstanding” was 51% and 41% among patients treated by IMRT and 3DCRT, respectively (p = 0.11). At 2 years, the corresponding percentages increased to 73% and 49%, respectively (p < 0.001). On multivariate analysis accounting for sex, age, radiation intent (definitive vs. postoperative), radiation dose, T stage, primary site, use of concurrent chemotherapy, and neck dissection, the use of IMRT was the only variable independently associated with improved quality of life (p = 0.01). Conclusion: The early quality of life improvements associated with IMRT not only are maintained but apparently become more magnified over time. These data provide powerful evidence attesting to the long-term benefits of IMRT for head-and-neck cancer.

  20. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  1. Effects of long-term environmental enrichment on anxiety, memory, hippocampal plasticity and overall brain gene expression in C57BL6 mice

    Directory of Open Access Journals (Sweden)

    Melanie Hüttenrauch

    2016-08-01

    Full Text Available There is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer’s disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging WT mice has not been studied in detail yet. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE paradigm for a duration of eleven months, leads to reduced anxiety and improved spatial reference memory in C57BL6 wildtype (WT mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH and EE mice, the number of dentate gyrus (DG neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders.

  2. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  3. Long-term biodosimetry Redux

    International Nuclear Information System (INIS)

    Simon, Steven L.; Bouville, Andre

    2016-01-01

    This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

  4. Long term high resolution rainfall runoff observations for improved water balance uncertainty and database QA-QC in the Walnut Gulch Experimental Watershed.

    Science.gov (United States)

    Bitew, M. M.; Goodrich, D. C.; Demaria, E.; Heilman, P.; Kautz, M. A.

    2017-12-01

    Walnut Gulch is a semi-arid environment experimental watershed and Long Term Agro-ecosystem Research (LTAR) site managed by USDA-ARS Southwest Watershed Research Center for which high-resolution long-term hydro-climatic data are available across its 150 km2 drainage area. In this study, we present the analysis of 50 years of continuous hourly rainfall data to evaluate runoff control and generation processes for improving the QA-QC plans of Walnut Gulch to create high-quality data set that is critical for reducing water balance uncertainties. Multiple linear regression models were developed to relate rainfall properties, runoff characteristics and watershed properties. The rainfall properties were summarized to event based total depth, maximum intensity, duration, the location of the storm center with respect to the outlet, and storm size normalized to watershed area. We evaluated the interaction between the runoff and rainfall and runoff as antecedent moisture condition (AMC), antecedent runoff condition (ARC) and, runoff depth and duration for each rainfall events. We summarized each of the watershed properties such as contributing area, slope, shape, channel length, stream density, channel flow area, and percent of the area of retention stock ponds for each of the nested catchments in Walnut Gulch. The evaluation of the model using basic and categorical statistics showed good predictive skill throughout the watersheds. The model produced correlation coefficients ranging from 0.4-0.94, Nash efficiency coefficients up to 0.77, and Kling-Gupta coefficients ranging from 0.4 to 0.98. The model predicted 92% of all runoff generations and 98% of no-runoff across all sub-watersheds in Walnut Gulch. The regression model also indicated good potential to complement the QA-QC procedures in place for Walnut Gulch dataset publications developed over the years since the 1960s through identification of inconsistencies in rainfall and runoff relations.

  5. Do mental health consumers want to improve their long-term disease risk behaviours? A survey of over 2000 psychiatric inpatients.

    Science.gov (United States)

    Bartlem, Kate; Bailey, Jacqueline; Metse, Alexandra; Asara, Ashley; Wye, Paula; Clancy, Richard; Wiggers, John; Bowman, Jenny

    2017-12-02

    Policies and clinical guidelines acknowledge the role mental health services have in addressing the physical health of individuals with a mental illness; however, little research has explored interest in reducing health risk behaviours or the acceptability of receiving support to reduce such risks among psychiatric inpatients. This study estimated the prevalence of four long-term disease risk behaviours (tobacco smoking, hazardous alcohol consumption, inadequate fruit and/or vegetable consumption, and inadequate physical activity); patient interest in reducing these risks; and acceptability of being provided care to do so during a psychiatric inpatient stay. A cross-sectional survey was undertaken with 2075 inpatients from four inpatient psychiatric facilities in one health district in Australia (October 2012-April 2014). Prevalence of risk behaviours ranged from 50.2% (inadequate physical activity) to 94.8% (inadequate fruit and/or vegetable consumption). The majority of respondents (88.4%) had more than one risk behaviour, and most were seriously considering improving their risk behaviours (47.6% to 65.3%). The majority (80.4%) agreed that it would be acceptable to be provided support and advice to change such behaviours during their psychiatric inpatient stay. Some diagnoses were associated with smoking and hazardous alcohol consumption, interest in reducing alcohol consumption and increasing fruit and/or vegetable consumption, and acceptability of receiving advice and support. The findings reinforce the need and opportunity for psychiatric inpatient facilities to address the long-term disease risk behaviours of their patients. © 2017 The Authors International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd on behalf of Australian College of Mental Health Nurses Inc.

  6. Evaluating long term forecasts

    Energy Technology Data Exchange (ETDEWEB)

    Lady, George M. [Department of Economics, College of Liberal Arts, Temple University, Philadelphia, PA 19122 (United States)

    2010-03-15

    The U.S. Department of Energy's Energy Information Administration (EIA), and its predecessor organizations, has published projections of U.S. energy production, consumption, distribution and prices annually for over 30 years. A natural issue to raise in evaluating the projections is an assessment of their accuracy compared to eventual outcomes. A related issue is the determination of the sources of 'error' in the projections that are due to differences between the actual versus realized values of the associated assumptions. One way to do this would be to run the computer-based model from which the projections are derived at the time the projected values are realized, using actual rather than assumed values for model assumptions; and, compare these results to the original projections. For long term forecasts, this approach would require that the model's software and hardware configuration be archived and available for many years, possibly decades, into the future. Such archival creates many practical problems; and, in general, it is not being done. This paper reports on an alternative approach for evaluating the projections. In the alternative approach, the model is run many times for cases in which important assumptions are changed individually and in combinations. A database is assembled from the solutions and a regression analysis is conducted for each important projected variable with the associated assumptions chosen as exogenous variables. When actual data are eventually available, the regression results are then used to estimate the sources of the differences in the projections of the endogenous variables compared to their eventual outcomes. The results presented here are for residential and commercial sector natural gas and electricity consumption. (author)

  7. Field performance of transgenic citrus trees: assessment of the long-term expression of uidA and nptII transgenes and its impact on relevant agronomic and phenotypic characteristics.

    Science.gov (United States)

    Pons, Elsa; Peris, Josep E; Peña, Leandro

    2012-07-15

    The future of genetic transformation as a tool for the improvement of fruit trees depends on the development of proper systems for the assessment of unintended effects in field-grown GM lines. In this study, we used eight transgenic lines of two different citrus types (sweet orange and citrange) transformed with the marker genes β-glucuronidase (uidA) and neomycin phosphotransferase II (nptII) as model systems to study for the first time in citrus the long-term stability of transgene expression and whether transgene-derived pleiotropic effects occur with regard to the morphology, development and fruit quality of orchard-grown GM citrus trees. The stability of the integration and expression of the transgenes was confirmed in 7-year-old, orchard-grown transgenic lines by Southern blot analysis and enzymatic assays (GUS and ELISA NPTII), respectively. Little seasonal variation was detected in the expression levels between plants of the same transgenic line in different organs and over the 3 years of analysis, confirming the absence of rearrangements and/or silencing of the transgenes after transferring the plants to field conditions. Comparisons between the GM citrus lines with their non-GM counterparts across the study years showed that the expression of these transgenes did not cause alterations of the main phenotypic and agronomic plant and fruit characteristics. However, when comparisons were performed between diploid and tetraploid transgenic citrange trees and/or between juvenile and mature transgenic sweet orange trees, significant and consistent differences were detected, indicating that factors other than their transgenic nature induced a much higher phenotypic variability. Our results indicate that transgene expression in GM citrus remains stable during long-term agricultural cultivation, without causing unexpected effects on crop characteristics. This study also shows that the transgenic citrus trees expressing the selectable marker genes that are most

  8. Does packaging with a calendar feature improve adherence to self-administered medication for long-term use? A systematic review.

    Science.gov (United States)

    Zedler, Barbara K; Kakad, Priyanka; Colilla, Susan; Murrelle, Lenn; Shah, Nirav R

    2011-01-01

    The therapeutic benefit of self-administered medications for long-term use is limited by an average 50% nonadherence rate. Patient forgetfulness is a common factor in unintentional nonadherence. Unit-of-use packaging that incorporates a simple day-and-date feature (calendar packaging) is designed to improve adherence by prompting patients to maintain the prescribed dosing schedule. To review systematically, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, randomized controlled trial evidence of the adherence benefits and harms of calendar blister packaging (CBP) and calendar pill organizers (CPO) for self-administered, long-term medication use. Data sources included the MEDLINE and Web of Science and Cochrane Library databases from their inception to September 2010 and communication with researchers in the field. Key search terms included blister-calendar pack, blister pack, drug packaging, medication adherence, medication compliance, medication compliance devices, medication containers, medication organizers, multicompartment compliance aid, persistence, pill-box organizers, prescription refill, randomized controlled trials, and refill compliance. Selected studies had an English-language title; a randomized controlled design; medication packaged in CBP or CPO; a requirement of solid, oral medication self-administered daily for longer than 1 month in community-dwelling adults; and at least 1 quantitative outcome measure of adherence. Two reviewers extracted data independently on study design, sample size, type of intervention and control, and outcomes. Ten trials with a total of 1045 subjects met the inclusion criteria, and 9 also examined clinical outcomes (seizures, blood pressure, psychiatric symptoms) or health care resource utilization. Substantial heterogeneity among trials precluded meta-analysis. In 3 studies, calendar packaging was part of a multicomponent adherence intervention. Six of 10 trials

  9. Short and long-term impact of lipectomy on expression profile of hepatic anabolic genes in rats: a high fat and high cholesterol diet-induced obese model.

    Directory of Open Access Journals (Sweden)

    Bey-Leei Ling

    Full Text Available OBJECTIVE: To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. METHODS: The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. RESULTS: No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, P<0.05 and negatively to glucose and insulin (r = -0.821 and -0.892 respectively, P<0.05. Eight weeks after the operation, the lipectomized animals revealed significant higher body and liver weights, weight gain, liver to body weight ratio, hepatic triacylglycerol and serum insulin level. CONCLUSIONS: In response to lipectomy a short term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These

  10. Improving long-term operation of power sources in off-grid hybrid systems based on renewable energy, hydrogen and battery

    Science.gov (United States)

    García, Pablo; Torreglosa, Juan P.; Fernández, Luis M.; Jurado, Francisco

    2014-11-01

    This paper presents two novel hourly energy supervisory controls (ESC) for improving long-term operation of off-grid hybrid systems (HS) integrating renewable energy sources (wind turbine and photovoltaic solar panels), hydrogen system (fuel cell, hydrogen tank and electrolyzer) and battery. The first ESC tries to improve the power supplied by the HS and the power stored in the battery and/or in the hydrogen tank, whereas the second one tries to minimize the number of needed elements (batteries, fuel cells and electrolyzers) throughout the expected life of the HS (25 years). Moreover, in both ESC, the battery state-of-charge (SOC) and the hydrogen tank level are controlled and maintained between optimum operating margins. Finally, a comparative study between the controls is carried out by models of the commercially available components used in the HS under study in this work. These ESC are also compared with a third ESC, already published by the authors, and based on reducing the utilization costs of the energy storage devices. The comparative study proves the right performance of the ESC and their differences.

  11. Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials

    Directory of Open Access Journals (Sweden)

    M. Kripp

    2015-01-01

    Full Text Available Purpose. The addition of cetuximab to radiochemotherapy (RCT failed to improve complete response rates in locally advanced rectal cancer (LARC. We report the long-term results in patients treated within two sequential clinical trials. Methods. Patients receiving neoadjuvant RCT using capecitabine and irinotecan (CapIri within a phase I/II trial or CapIri + cetuximab within a phase II trial were evaluated for analysis of disease-free survival (DFS and overall survival (OS. KRAS exon 2 mutational status had been analyzed in patients receiving cetuximab. Results. 37 patients from the CapIri trial and 49 patients from the CapIri-cetuximab treatment group were evaluable. Median follow-up time was 75.2 months. The 5-year DFS rate was 82% (CapIri and 79% (CapIri-cetuximab (P=0.62. The median OS was 127.4 months. 5-year OS was 73% for both groups (CapIri and CapIri-cetuximab (P=0.61. No significant difference in DFS (P=0.86 or OS (P=0.39 was noticed between patients receiving CapIri and those receiving CapIri-cetuximab with KRAS wild-type tumors. Conclusions. As the addition of cetuximab did not improve neither DFS nor OS it should not play a role in the perioperative treatment of patients with LARC, not even of patients with (KRAS WT tumors.

  12. A risk-informed approach of quantification of epistemic uncertainty for the long-term radioactive waste disposal. Improving reliability of expert judgements with an advanced elicitation procedure

    International Nuclear Information System (INIS)

    Sugiyama, Daisuke; Chida, Taiji; Fujita, Tomonari; Tsukamoto, Masaki

    2011-01-01

    A quantification methodology of epistemic uncertainty by expert judgement based on the risk-informed approach is developed to assess inevitable uncertainty for the long-term safety assessment of radioactive waste disposal. The proposed method in this study employs techniques of logic tree, by which options of models and/or scenarios are identified, and Evidential Support Logic (ESL), by which possibility of each option is quantified. In this report, the effect of a feedback process of discussion between experts and input of state-of-the-art knowledge in the proposed method is discussed to estimate alteration of the distribution of expert judgements which is one of the factors causing uncertainty. In a preliminary quantification experiment of uncertainty of degradation of the engineering barrier materials in a tentative sub-surface disposal using the proposed methodology, experts themselves modified questions appropriately to facilitate sound judgements and to correlate those with scientific evidences clearly. The result suggests that the method effectively improves confidence of expert judgement. Also, the degree of consensus of expert judgement was sort of improved in some cases, since scientific knowledge and information of expert judgement in other fields became common understanding. It is suggested that the proposed method could facilitate consensus on uncertainty between interested persons. (author)

  13. Sustained Improvement of Arterial Stiffness and Blood Pressure after Long-Term Rosuvastatin Treatment in Patients with Inflammatory Joint Diseases: Results from the RORA-AS Study.

    Directory of Open Access Journals (Sweden)

    Eirik Ikdahl

    Full Text Available Patients with inflammatory joint diseases (IJD have a high prevalence of hypertension and increased arterial stiffness. The aim of the present study was to evaluate the effect of long-term rosuvastatin treatment on arterial stiffness, measured by augmentation index (AIx and aortic pulse wave velocity (aPWV, and blood pressure (BP in IJD patients with established atherosclerosis.Eighty-nine statin naïve IJD patients with carotid atherosclerotic plaque(s (rheumatoid arthritis n = 55, ankylosing spondylitis n = 23, psoriatic arthritis n = 11 received rosuvastatin for 18 months to achieve low-density lipoprotein cholesterol goal ≤1.8 mmol/L. Change in AIx (ΔAIx, aPWV (ΔaPWV, systolic BP (ΔsBP and diastolic BP (ΔdBP from baseline to study end was assessed by paired samples t-tests. Linear regression was applied to evaluate associations between cardiovascular disease (CVD risk factors, rheumatic disease specific variables and medication, and ΔAIx, ΔaPWV, ΔsBP and ΔdBP.AIx, aPWV, sBP and dBP were significantly reduced from baseline to study end. The mean (95%CI changes were: ΔAIx: -0.34 (-0.03, -0.65% (p = 0.03, ΔaPWV: -1.69 (-0.21, -3.17 m/s2 (p = 0.03, ΔsBP: -5.27 (-1.61, -8.93 mmHg (p = 0.004 and ΔdBP -2.93 (-0.86, -5.00 mmHg (p = 0.01. In linear regression models, ∆aPWV was significantly correlated with ΔsBP and ΔdBP (for all: p<0.001.There is an unmet need of studies evaluating CVD prevention in IJD patients. We have shown for the first time that long-term intensive lipid lowering with rosuvastatin improved arterial stiffness and induced a clinically significant BP reduction in patients with IJD. These improvements were linearly correlated and may represent novel insight into the pleiotropic effects by statins.ClinicalTrials.gov NCT01389388.

  14. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression.

    Science.gov (United States)

    Ferris, Robert L; Blumenschein, George; Fayette, Jerome; Guigay, Joel; Colevas, A Dimitrios; Licitra, Lisa; Harrington, Kevin J; Kasper, Stefan; Vokes, Everett E; Even, Caroline; Worden, Francis; Saba, Nabil F; Docampo, Lara Carmen Iglesias; Haddad, Robert; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Lynch, Mark; Jayaprakash, Vijayvel; Li, Li; Gillison, Maura L

    2018-06-01

    We report 2-year results from CheckMate 141 to establish the long-term efficacy and safety profile of nivolumab and outcomes by tumor PD-L1 expression in patients with recurrent or metastatic (R/M),platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). Patients with R/M SCCHN with tumor progression/recurrence within 6 months of platinum therapy were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC). Primary endpoint: overall survival (OS). Data cutoff: September 2017. With 24.2 months' minimum follow-up, nivolumab (n = 240) continued to improve OS vs IC (n = 121), hazard ratio (HR) = 0.68 (95% CI 0.54-0.86). Nivolumab nearly tripled the estimated 24-month OS rate (16.9%) vs IC (6.0%), and demonstrated OS benefit across patients with tumor PD-L1 expression ≥1% (HR [95% CI] = 0.55 [0.39-0.78]) and  < 1% (HR [95% CI] = 0.73 [0.49-1.09]), and regardless of tumor HPV status. Estimated OS rates at 18, 24, and 30 months with nivolumab were consistent irrespective of PD-L1 expression (<1%/≥1%). In the nivolumab arm, there were no observed differences in baseline characteristics or safety profile between long-term survivors and the overall population. Grade 3-4 treatment-related adverse event rates were 15.3% and 36.9% for nivolumab and IC, respectively. Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636). Copyright © 2018. Published by Elsevier Ltd.

  15. Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.

    Science.gov (United States)

    Stevens, Karen E; Choo, Kevin S; Stitzel, Jerry A; Marks, Michael J; Adams, Catherine E

    2014-03-13

    Perinatal choline supplementation has produced several benefits in rodent models, from improved learning and memory to protection from the behavioral effects of fetal alcohol exposure. We have shown that supplemented choline through gestation and lactation produces long-term improvement in deficient sensory inhibition in DBA/2 mice which models a similar deficit in schizophrenia patients. The present study extends that research by feeding normal or supplemented choline diets to DBA/2 mice carrying the null mutation for the α7 nicotinic receptor gene (Chrna7). DBA/2 mice heterozygotic for Chrna7 were bred together. Dams were placed on supplemented (5 gm/kg diet) or normal (1.1 gm/kg diet) choline at mating and remained on the specific diet until offspring weaning. Thereafter, offspring were fed standard rodent chow. Adult offspring were assessed for sensory inhibition. Brains were obtained to ascertain hippocampal α7 nicotinic receptor levels. Choline-supplemented mice heterozygotic or null-mutant for Chrna7 failed to show improvement in sensory inhibition. Only wildtype choline-supplemented mice showed improvement with the effect solely through a decrease in test amplitude. This supports the hypothesis that gestational-choline supplementation is acting through the α7 nicotinic receptor to improve sensory inhibition. Although there was a significant gene-dose-related change in hippocampal α7 receptor numbers, binding studies did not reveal any choline-dose-related change in binding in any hippocampal region, the interaction being driven by a significant genotype main effect (wildtype>heterozygote>null mutant). These data parallel a human study wherein the offspring of pregnant women receiving choline supplementation during gestation, showed better sensory inhibition than offspring of women on placebo. Published by Elsevier B.V.

  16. Long Term Financing of Infrastructure

    OpenAIRE

    Sinha, Sidharth

    2014-01-01

    Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

  17. Changes in soil physical and chemical properties in long term improved natural and traditional agroforestry management systems of cacao genotypes in Peruvian Amazon.

    Science.gov (United States)

    Arévalo-Gardini, Enrique; Canto, Manuel; Alegre, Julio; Loli, Oscar; Julca, Alberto; Baligar, Virupax

    2015-01-01

    Growing cacao (Theobroma cacao L.) in an agroforestry system generates a productive use of the land, preserves the best conditions for physical, chemical and biological properties of tropical soils, and plays an important role in improving cacao production and fertility of degraded tropical soils. The aim of this study was to evaluate the impact of two long term agroforestry systems of cacao management on soil physical and chemical properties in an area originally inhabited by 30 years old native secondary forest (SF). The two agroforestry systems adapted were: improved natural agroforestry system (INAS) where trees without economic value were selectively removed to provide 50% shade and improved traditional agroforestry system (ITAS) where all native trees were cut and burnt in the location. For evaluation of the changes of soil physical and chemical properties with time due to the imposed cacao management systems, plots of 10 cacao genotypes (ICS95, UF613, CCN51, ICT1112, ICT1026, ICT2162, ICT2171, ICT2142, H35, U30) and one plot with a spontaneous hybrid were selected. Soil samples were taken at 0-20, 20-40 and 40-60 cm depths before the installation of the management systems (2004), and then followed at two years intervals. Bulk density, porosity, field capacity and wilting point varied significantly during the years of assessment in the different soil depths and under the systems assessed. Soil pH, CEC, exchangeable Mg and sum of the bases were higher in the INAS than the ITAS. In both systems, SOM, Ext. P, K and Fe, exch. K, Mg and Al+H decreased with years of cultivation; these changes were more evident in the 0-20 cm soil depth. Overall improvement of SOM and soil nutrient status was much higher in the ITAS than INAS. The levels of physical and chemical properties of soil under cacao genotypes showed a marked difference in both systems.

  18. Long-Term Improvement of Neurological Signs and Metabolic Dysfunction in a Mouse Model of Krabbe's Disease after Global Gene Therapy.

    Science.gov (United States)

    Marshall, Michael S; Issa, Yazan; Jakubauskas, Benas; Stoskute, Monika; Elackattu, Vince; Marshall, Jeffrey N; Bogue, Wil; Nguyen, Duc; Hauck, Zane; Rue, Emily; Karumuthil-Melethil, Subha; Zaric, Violeta; Bosland, Maarten; van Breemen, Richard B; Givogri, Maria I; Gray, Steven J; Crocker, Stephen J; Bongarzone, Ernesto R

    2018-03-07

    We report a global adeno-associated virus (AAV)9-based gene therapy protocol to deliver therapeutic galactosylceramidase (GALC), a lysosomal enzyme that is deficient in Krabbe's disease. When globally administered via intrathecal, intracranial, and intravenous injections to newborn mice affected with GALC deficiency (twitcher mice), this approach largely surpassed prior published benchmarks of survival and metabolic correction, showing long-term protection of demyelination, neuroinflammation, and motor function. Bone marrow transplantation, performed in this protocol without immunosuppressive preconditioning, added minimal benefits to the AAV9 gene therapy. Contrasting with other proposed pre-clinical therapies, these results demonstrate that achieving nearly complete correction of GALC's metabolic deficiencies across the entire nervous system via gene therapy can have a significant improvement to behavioral deficits, pathophysiological changes, and survival. These results are an important consideration for determining the safest and most effective manner for adapting gene therapy to treat this leukodystrophy in the clinic. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  19. Long-term Saxagliptin Treatment Improves Endothelial Function but not Pulse Wave Velocity and Intima-Media Thickness in Type 2 Diabetic Patients.

    Science.gov (United States)

    Dell'Oro, Raffaella; Maloberti, Alessandro; Nicoli, Francesco; Villa, Paolo; Gamba, Pierluigi; Bombelli, Michele; Mancia, Giuseppe; Grassi, Guido

    2017-12-01

    Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes. We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables. In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls. The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process.

  20. Impact of protein supplementation and exercise in preventing changes in gene expression profiling in woman muscles after long-term bedrest as revealed by microarray analysis.

    Science.gov (United States)

    Chopard, Angele; Lecunff, Martine; Danger, Richard; Teusan, Raluca; Jasmin, Bernard J.; Marini, Jean-Francois; Leger, Jean

    Long duration space flights have a dramatic impact on human physiology and under such a condition, skeletal muscles are known to be one of the most affected systems. A thorough understanding of the basic mechanisms leading to muscle impairment under microgravity, which causes significant loss of muscle mass as well as structural disorders, is necessary for the development of efficient space flight countermeasures. This study was conducted under the aegis of the European Space Agency (ESA), the National Aeronautics and Space Administration of the USA (NASA), the Canadian Space Agency (CSA), and the French "Centre National d'Etudes Spatiales" (CNES). It gave us the opportunity to investigate for the first time the effects of prolonged disuse (long-term bedrest, LTBR) on the transcriptome of different muscle types in healthy women (control, n=8), as well as the potential beneficial impact of protein supplementation (nutrition, n=8) and a combined resistance and aerobic exercise training program (exercise, n=8). Pre- (LTBR -8) and post- (LTBR +59) biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles from each subject. Skeletal muscle gene expression profiles were obtained using a custom made microarray containing 6681 muscle-relevant genes. 555 differentiallyexpressed and statistically-significant genes were identified in control group following 60 days of LTBR, including 348 specific for SOL, 83 specific for VL, and 124 common for the two types of muscle (p<0.05). After LTBR, both muscle types exhibited a consistent decrease in pathways involved in fatty acid oxidation, ATP synthesis, and oxidative phosphorylation (p<0.05). However, the postural SOL muscle exhibited a higher level of changes with mRNA encoding proteins involved in protein synthesis and activation of protein degradation (mainly ubiquitinproteasome components) (p<0.05). Major changes in muscle function, such as those involved in calcium signaling and muscle structure including

  1. [Prognostic prediction of the functional capacity and effectiveness of functional improvement program of the musculoskeletal system among users of preventive care service under long-term care insurance].

    Science.gov (United States)

    Sone, Toshimasa; Nakaya, Naoki; Tomata, Yasutake; Aida, Jun; Okubo, Ichiro; Ohara, Satoko; Obuchi, Shuichi; Sugiyama, Michiko; Yasumura, Seiji; Suzuki, Takao; Tsuji, Ichiro

    2013-01-01

    The purpose of this study was to examine the effectiveness of the Functional Improvement Program of the Musculoskeletal System among users of Preventive Care Service under Long-Term Care Insurance. A total of 3,073 subjects were analyzed. We used the prediction formula to estimate the predicted value of the Kihon Checklist after one year, and calculated the measured value minus the predicted value. The subjects were divided into two groups according to the measured value minus predicted value tertiles: the lowest and middle tertile (good-to-fair measured value) and the highest tertile (poor measured value). We used a multiple logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of the good-to-fair measured values of the Kihon Checklist after one year, according to the Functional Improvement Program of the Musculoskeletal System. In potentially dependent elderly, the multivariate adjusted ORs (95% CI) of the good-to-fair measured values were 2.4 (1.3-4.4) for those who attended the program eight times or more in a month (vs those who attended it three times or less in a month), 1.3 (1.0-1.8) for those who engaged in strength training using machines (vs those who did not train), and 1.4 (1.0-1.9) for those who engaged in endurance training. In this study, among potentially dependent elderly, those who attended the program eight times or more in a month and those who engaged in strength training using machines or endurance training showed a significant improvement of their functional capacity.

  2. Long-term urethral catheterisation.

    Science.gov (United States)

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  3. Long-term assessment at field scale of Floating Treatment Wetlands for improvement of water quality and provision of ecosystem services in a eutrophic urban pond.

    Science.gov (United States)

    Olguín, Eugenia J; Sánchez-Galván, Gloria; Melo, Francisco J; Hernández, Víctor J; González-Portela, Ricardo E

    2017-04-15

    Pollution of urban water bodies requires stringent control measures and the development of low-cost and highly efficient alternative technologies. In contrast to Constructed Wetlands, Floating Treatment Wetlands (FTWs) have the advantage of not requiring large surface of land since they operate in situ. However, there is limited information about their long-term evaluation while operating at field scale. The aim of this work was to assess the performance of FTWs using a combination of Pontederia sagittata and Cyperus papyrus for the improvement of the water quality and provision of ecosystem services of a eutrophic urban pond. The FTWs were built with low-cost material easy to acquire and to ensemble. Two FTWs (17.5m 2 and 33m 2 ) located in Pond 1 within a complex of 4 urban artificial ponds were evaluated for two years. They promoted an increase in the dissolved oxygen (D.O.) within a range of 15 to 67%, a removal of fecal coliforms in the range of 9 to 86% and a nitrate removal in the range of 9 to 76%. The plant productivity reached a maximum of 363g dm m -2 d -1 in the FTW1 and 536g dm m -2 d -1 in the FTW2 during the period March-June 2016. The TKN and the TP content in the plant were in the range of 18.3 to 28.1 and of 0.05 to 0.196gkg -1 dry matter, respectively. In conclusion, the tested FTWs have proved to be a very beneficial low-cost technology for the improvement of water quality and provision of ecosystem services. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies.

    Science.gov (United States)

    Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi; Huang, Tao; Ma, Wenjie; Rimm, Eric B; Manson, JoAnn E; Hu, Frank B; Willett, Walter C; Qi, Lu

    2018-01-10

    To investigate whether improving adherence to healthy dietary patterns interacts with the genetic predisposition to obesity in relation to long term changes in body mass index and body weight. Prospective cohort study. Health professionals in the United States. 8828 women from the Nurses' Health Study and 5218 men from the Health Professionals Follow-up Study. Genetic predisposition score was calculated on the basis of 77 variants associated with body mass index. Dietary patterns were assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (AMED). Five repeated measurements of four year changes in body mass index and body weight over follow-up (1986 to 2006). During a 20 year follow-up, genetic association with change in body mass index was significantly attenuated with increasing adherence to the AHEI-2010 in the Nurses' Health Study (P=0.001 for interaction) and Health Professionals Follow-up Study (P=0.005 for interaction). In the combined cohorts, four year changes in body mass index per 10 risk allele increment were 0.07 (SE 0.02) among participants with decreased AHEI-2010 score and -0.01 (0.02) among those with increased AHEI-2010 score, corresponding to 0.16 (0.05) kg versus -0.02 (0.05) kg weight change every four years (Pdietary patterns could attenuate the genetic association with weight gain. Moreover, the beneficial effect of improved diet quality on weight management was particularly pronounced in people at high genetic risk for obesity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies

    Science.gov (United States)

    Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi; Huang, Tao; Ma, Wenjie; Rimm, Eric B; Manson, JoAnn E; Hu, Frank B; Willett, Walter C

    2018-01-01

    Abstract Objective To investigate whether improving adherence to healthy dietary patterns interacts with the genetic predisposition to obesity in relation to long term changes in body mass index and body weight. Design Prospective cohort study. Setting Health professionals in the United States. Participants 8828 women from the Nurses’ Health Study and 5218 men from the Health Professionals Follow-up Study. Exposure Genetic predisposition score was calculated on the basis of 77 variants associated with body mass index. Dietary patterns were assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (AMED). Main outcome measures Five repeated measurements of four year changes in body mass index and body weight over follow-up (1986 to 2006). Results During a 20 year follow-up, genetic association with change in body mass index was significantly attenuated with increasing adherence to the AHEI-2010 in the Nurses’ Health Study (P=0.001 for interaction) and Health Professionals Follow-up Study (P=0.005 for interaction). In the combined cohorts, four year changes in body mass index per 10 risk allele increment were 0.07 (SE 0.02) among participants with decreased AHEI-2010 score and −0.01 (0.02) among those with increased AHEI-2010 score, corresponding to 0.16 (0.05) kg versus −0.02 (0.05) kg weight change every four years (Pdietary patterns could attenuate the genetic association with weight gain. Moreover, the beneficial effect of improved diet quality on weight management was particularly pronounced in people at high genetic risk for obesity. PMID:29321156

  6. LONG TERM COLLECTIONS

    CERN Multimedia

    2004-01-01

    The Committee would like to thank all those, from near and far, who kindly gave donations to the collection organized at the time of the sudden death of our friend and colleague Stephen O'NEALE The sum of 3,615 francs will be sent to the INEPE Association for the education of children in Quito, Ecuador. We are deeply grateful for this gesture from Steve's family and hope that they find comfort in knowing that Steve's memory will live on through the children whose daily lives will be improved by this gift.

  7. Accessibility Long Term Perspectives

    Directory of Open Access Journals (Sweden)

    Kay Axhausen

    2008-11-01

    Full Text Available Improved accessibility and its correlate lower generalized cost of contact, travel and transport have been sought by dynamic human societies for their economic and social benefits through- out recorded history. The paper will reflect about this process at a number of different spatial and temporal scales based on a conceptual model. Looking back at European history, it will trace the interaction between Christaller's logic of local market areas and the idea of (low contact cost network cities. Focusing on Switzerland since 1950 it will show how network investment changed the relative distribution of population and employment and how this interacted with changes in the preferences of the travelers. Using a recent snapshot of how a substantial sample of Swiss maintain their social networks over often very large areas, it will try to answer the question of what will happen in the future, if the current trend of ever lower costs of contact will persist.

  8. A Decade of Improvements for Solid Oxide Electrolysis Cells. Long-Term Degradation Rate from 40%/Kh to 0.4 % Kh

    DEFF Research Database (Denmark)

    Hauch, Anne; Brodersen, Karen; Chen, Ming

    2016-01-01

    Solid oxide electrolysis cells (SOEC) have the potential for efficient large-scale conversion from electrical energy to chemical energy stored in fuels, such as hydrogen or synthetic hydrocarbon fuels by use of well-known catalysis processes. Key issues for the break-through of this technology...... are to provide inexpensive, reliable, high performing and long-term stable SOEC for stack and system applications. At DTU Energy (formerly Department of Fuel Cells and Solid State Chemistry, Risø National Laboratory), research within SOEC for more than a decade has led to long-term degradation rates on cell...

  9. Long-term follow-up of a randomized controlled trial on additional core stability exercises training for improving dynamic sitting balance and trunk control in stroke patients.

    Science.gov (United States)

    Cabanas-Valdés, Rosa; Bagur-Calafat, Caritat; Girabent-Farrés, Montserrat; Caballero-Gómez, Fernanda Mª; du Port de Pontcharra-Serra, Helena; German-Romero, Ana; Urrútia, Gerard

    2017-11-01

    Analyse the effect of core stability exercises in addition to conventional physiotherapy training three months after the intervention ended. A randomized controlled trial. Outpatient services. Seventy-nine stroke survivors. In the intervention period, both groups underwent conventional physiotherapy performed five days/week for five weeks, and in addition the experimental group performed core stability exercises for 15 minutes/day. Afterwards, during a three-month follow-up period, both groups underwent usual care that could eventually include conventional physiotherapy or physical exercise but not in a controlled condition. Primary outcome was trunk control and dynamic sitting balance assessed by the Spanish-Version of Trunk Impairment Scale 2.0 and Function in Sitting Test. Secondary outcomes were standing balance and gait evaluated by the Berg Balance Scale, Tinetti Test, Brunel Balance Assessment, Spanish-Version of Postural Assessment Scale for Stroke and activities of daily living using the Barthel Index. A total of 68 subjects out of 79 completed the three-month follow-up period. The mean difference (SD) between groups was 0.78 (1.51) points ( p = 0.003) for total score on the Spanish-Version of Trunk Impairment Scale 2.0, 2.52 (6.46) points ( p = 0.009) for Function in Sitting Test, dynamic standing balance was 3.30 (9.21) points ( p= 0.009) on the Berg Balance Scale, gait was 0.82 (1.88) points ( p = 0.002) by Brunel Balance Assessment (stepping), and 1.11 (2.94) points ( p = 0.044) by Tinetti Test (gait), all in favour of core stability exercises. Core stability exercises plus conventional physiotherapy have a positive long-term effect on improving dynamic sitting and standing balance and gait in post-stroke patients.

  10. Referral for psychological therapy of people with long term conditions improves adherence to antidepressants and reduces emergency department attendance: Controlled before and after study

    Science.gov (United States)

    de Lusignan, Simon; Chan, Tom; Tejerina Arreal, Maria C.; Parry, Glenys; Dent-Brown, Kim; Kendrick, Tony

    2013-01-01

    Background Referral to psychological therapies is recommended for people with common mental health problems (CMHP) however its impact on healthcare utilisation in people with long term conditions (LTCs) is not known. Method Routinely collected primary care, psychological therapy clinic and hospital data were extracted for the registered population of 20 practices (N = 121199). These data were linked using the SAPREL (Secure and Private Record Linkage) method. We linked the 1118 people referred to psychological therapies with 6711 controls, matched for age, gender and practice. We compared utilisation of healthcare resources by people with LTCs, 6 months before and after referral, and conducted a controlled before and after study to compare health utilisation with controls. We made the assumption that collection of a greater number of repeat prescriptions for antidepressants was associated with greater adherence. Results Overall 21.8% of people with an LTC had CMHP vs. 18.8% without (p < 0.001). People with LTCs before referral were more likely to use health care resources (2-tailed t-test p < 0.001). Cases with LTCs showed referral to the psychological therapies clinic was associated with increased antidepressant medication prescribing (mean differences 0.62, p < 0.001) and less use of emergency department than controls (mean difference −0.21, p = 0.003). Conclusions Referral to improved access to psychological therapies (IAPT) services appears of value to people with LTC. It is associated with the issue of a greater number of prescriptions for anti-depressant medicines and less use of emergency services. Further studies are needed to explore bed occupancy and outpatient attendance. PMID:23639304

  11. Developing a Validated Long-Term Satellite-Based Albedo Record in the Central Alaska Range to Improve Regional Hydroclimate Reconstructions

    Science.gov (United States)

    Kreutz, K. J.; Godaire, T. P.; Burakowski, E. A.; Winski, D.; Campbell, S. W.; Wang, Z.; Sun, Q.; Hamilton, G. S.; Birkel, S. D.; Wake, C. P.; Osterberg, E. C.; Schaaf, C.

    2015-12-01

    Mountain glaciers around the world, particularly in Alaska, are experiencing significant surface mass loss from rapid climatic shifts and constitute a large proportion of the cryosphere's contribution to sea level rise. Surface albedo acts as a primary control on a glacier's mass balance, yet it is difficult to measure and quantify spatially and temporally in steep, mountainous settings. During our 2013 field campaign in Denali National Park to recover two surface to bedrock ice cores, we used an Analytical Spectral Devices (ASD) FieldSpec4 Standard Resolution spectroradiometer to measure incoming solar radiation, outgoing surface reflectance and optical grain size on the Kahiltna Glacier and at the Kahiltna Base Camp. A Campbell Scientific automatic weather station was installed on Mount Hunter (3900m) in June 2013, complementing a longer-term (2008-present) station installed at Kahiltna Base Camp (2100m). Use of our in situ data aids in the validation of surface albedo values derived from Moderate Resolution Imaging Spectroradiometer (MODIS) and Landsat satellite imagery. Comparisons are made between ASD FieldSpec4 ground measurements and 500m MODIS imagery to assess the ability of MODIS to capture the variability of surface albedo across the glacier surface. The MODIS MCD43A3 BRDF/Albedo Product performs well at Kahiltna Base Camp (albedo (10-28% relative to ASD data) appear to occur along the Kahiltna Glacier due to the snow-free valley walls being captured in the 500m MODIS footprint. Incorporating Landsat imagery will strengthen our interpretations and has the potential to produce a long-term (1982-present) validated satellite albedo record for steep and mountainous terrain. Once validation is complete, we will compare the satellite-derived albedo record to the Denali ice core accumulation rate, aerosol records (i.e. volcanics and biomass burning), and glacier mass balance data. This research will ultimately contribute to an improved understanding of the

  12. Does outpatient physical therapy with the aim of improving health-related physical fitness influence the level of physical activity in patients with long-term musculoskeletal conditions?

    Science.gov (United States)

    Holm, I; Tveter, A T; Moseng, T; Dagfinrud, H

    2015-09-01

    To evaluate any change in self-reported level of physical activity in patients receiving a general physical exercise programme in addition to disease-specific physiotherapy treatment. Pre-post-intervention study. Outpatient physiotherapy clinics. One hundred and ninety patients with long-term musculoskeletal conditions attending outpatient physiotherapy were recruited from seven physiotherapy clinics. Physiotherapy including disease-specific modalities and a general individually tailored exercise programme. Patients were evaluated at baseline and at the end of the programme. International Physical Activity Questionnaire short form (IPAQ-sf) and COOP WONCA functional assessment charts. Forty-two patients were excluded from the analysis because they did not complete the IPAQ-sf correctly or dropped out during the treatment period. There was a significant increase in the number of metabolic equivalent task (MET)-min/week for vigorous and moderate-intensity activities, walking and total physical activity. The number of exercise sessions per week increased from 1.8 [standard deviation (SD) 0.9] to 2.2 (SD 1.2) (P=0.001). The proportion of patients with a low level of physical activity decreased by 12%, and the proportion of the participants who did not/could not exercise decreased from 26% to 8%. The COOP WONCA charts showed significant improvements in the physical fitness, feelings, daily activities and social activities items. A significant increase was found in the number of MET-min/week for all activity levels. Therefore, a general physical exercise programme initiated by a physiotherapist led to a positive change in level of physical activity. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  13. Do interventions with staff in long-term residential facilities improve quality of care or quality for life people with dementia? A systematic review of the evidence.

    Science.gov (United States)

    Bird, Mike; Anderson, Katrina; MacPherson, Sarah; Blair, Annaliese

    2016-12-01

    Common sense suggests and research indicates relationships between staff factors in residential dementia care and quality of life (QOL) for residents, with poor care increasing suffering. However, we do not have a coherent picture of which staff interventions have an impact on quality of care (QOC) or resident QOL. A comprehensive search of 20 years' peer-reviewed literature using Medline, PsycINFO, Embase, PubMed, CINAHL, and the Cochrane, Campbell Collaboration identified 4,760 studies meriting full text review. Forty-six met the inclusion criteria, namely interventions in long-term facilities helping staff develop their capacity to provide better care and/or QOL for residents with dementia. Thirty-five other papers comprised an associated predictor review. Conclusions from these limited data are further compromised because nine studies failed to measure effects on residents and only half assessed effects after the project team withdrew. Of these, excellent studies produced change over the medium (3-4 months) or longer term, including reduction in challenging behavior and restraint use but this applied only to a minority. A number of studies failed to measure effects on QOC, limiting conclusions about mechanisms underlying change. In general, level of intervention required depended on the target. For outcomes like restraint use, structured education sessions with some support appear adequate. Programs to reduce pain require more support. For complicated issues like challenging behavior and increasing co-operation in showering, detailed, supportive, on-site interventions are required. Improvements in restraint and staff/resident interactions were the most promising findings. (Review registration number: PROSPERO 2014:CRD42014015224).

  14. Statistical package for improved analysis of hillslope monitoring data collected as part of the Board of Forestry's long-term monitoring program

    Science.gov (United States)

    Jack Lewis; Jim Baldwin

    1997-01-01

    The State of California has embarked upon a Long-Term Monitoring Program whose primary goal is to assess the effectiveness of the Forest Practice Rules and Review Process in protecting the beneficial uses of waters from the impacts of timber operations on private timberlands. The Board of Forestry's Monitoring Study Group concluded that hillslope monitoring should...

  15. Rolls-Royce I and C long term support a dedicated solution to manage plant condition, optimize operating life and maximize plant value while improving safety

    International Nuclear Information System (INIS)

    Baillonmartos, F.

    2010-01-01

    Rolls-Royce supplied safety I and C equipment as Original Equipment Manufacturer (OEM) for 200 reactors in operation from 1970', including various technological steps (analog to digital hardware). The hardware scope covers various systems, either more than 500 hardware references, either more than 150000 parts in operation. Rolls-Royce contributes to life time extension ensuring system availability and reliability on long term basis by determining the optimum solution between different maintenance approaches: maintenance and repair with limited retrofit or major system retrofit. Based on Long Term Support (LTS) agreement with customers, Rolls-Royce commits to maintain the capability to manufacture, modify, repair, test, at board, rack and systems level over a long time period. This means finding solution to hardware ageing, technology evolution, skills and tools maintenance. This paper describes how Rolls-Royce has built a global process based on delivering a package of services and developing long term support engineering solutions and tools. Our main experience on EDF partnership will serve to illustrate Rolls-Royce I and C Long Term Support activity. (authors)

  16. An Evidence-Based Cue-Selection Guide and Logic Model to Improve Pressure Ulcer Prevention in Long-term Care.

    Science.gov (United States)

    Yap, Tracey L; Kennerly, Susan M; Bergstrom, Nancy; Hudak, Sandra L; Horn, Susan D

    2016-01-01

    Pressure ulcers have consistently resisted prevention efforts in long-term care facilities nationwide. Recent research has described cueing innovations that-when selected according to the assumptions and resources of particular facilities-support best practices of pressure ulcer prevention. This article synthesizes that research into a unified, dynamic logic model to facilitate effective staff implementation of a pressure ulcer prevention program.

  17. [Oral health hygiene education programme for nursing personnel to improve oral health of residents in long-term care facilities 2010 in Frankfurt/Main, Germany].

    Science.gov (United States)

    Czarkowski, G; Allroggen, S; Köster-Schmidt, A; Bausback-Schomakers, S; Frank, M; Heudorf, U

    2013-06-01

    demonstrated, significant for plaque index, cleanliness of the tongue and denture hygiene index. The positive assessment of the nursing personnel as well as the positive effects on oral hygiene in the residents are in agreement with the results of many other studies in many countries. Therefore, these education programmes will be continued in the long-term care facilities in Frankfurt/Main, Germany.· © Georg Thieme Verlag KG Stuttgart · New York.

  18. MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

    Science.gov (United States)

    Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

    2014-01-01

    Purpose Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Patients and Methods Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Results Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Conclusions Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

  19. MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

    Directory of Open Access Journals (Sweden)

    Thomas Pavelitz

    Full Text Available Colon cancers deficient in mismatch repair (MMR may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Cancer and Leukemia Group B 89803 (Alliance randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV or irinotecan+FU/LV (IFL, with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS, and a secondary endpoint was disease-free survival (DFS. Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.Of 625 tumor cases examined, 70 (11.2% exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11. In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.ClinicalTrials.gov NCT00003835.

  20. Long term complications of diabetes

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  1. Epidural analgesia during open radical prostatectomy does not improve long-term cancer-related outcome: a retrospective study in patients with advanced prostate cancer.

    Directory of Open Access Journals (Sweden)

    Patrick Y Wuethrich

    Full Text Available BACKGROUND: A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. METHODS: In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP with general anesthesia combined with intra- and postoperative epidural analgesia (n=67 or with postoperative ketorolac-morphine analgesia (n=81 were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs. Biochemical recurrence (BCR-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. RESULTS: The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07. For both groups, higher preoperative PSA (hazard ratio (HR 1.02, 95% confidence interval (CI 1.01-1.02, P<0.0001, increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007 and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04 were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001. CONCLUSIONS: General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.

  2. Ibuprofen-in-cyclodextrin-in-W/O/W emulsion - Improving the initial and long-term encapsulation efficiency of a model active ingredient.

    Science.gov (United States)

    Hattrem, Magnus N; Kristiansen, Kåre A; Aachmann, Finn L; Dille, Morten J; Draget, Kurt I

    2015-06-20

    A challenge in formulating water-in-oil-in-water (W/O/W) emulsions is the uncontrolled release of the encapsulated compound prior to application. Pharmaceuticals and nutraceuticals usually have amphipathic nature, which may contribute to leakage of the active ingredient. In the present study, cyclodextrins (CyDs) were used to impart a change in the relative polarity and size of a model compound (ibuprofen) by the formation of inclusion complexes. Various inclusion complexes (2-hydroxypropyl (HP)-β-CyD-, α-CyD- and γ-CyD-ibuprofen) were prepared and presented within W/O/W emulsions, and the initial and long-term encapsulation efficiency was investigated. HP-β-CyD-ibuprofen provided the highest encapsulation of ibuprofen in comparison to a W/O/W emulsion with unassociated ibuprofen confined within the inner water phase, with a four-fold increase in the encapsulation efficiency. An improved, although lower, encapsulation efficiency was obtained for the inclusion complex γ-CyD-ibuprofen in comparison to HP-β-CyD-ibuprofen, whereas α-CyD-ibuprofen had a similar encapsulation efficiency to that of unassociated ibuprofen. The lower encapsulation efficiency of ibuprofen in combination with α-CyD and γ-CyD was attributed to a lower association constant for the γ-CyD-ibuprofen inclusion complex and the ability of α-CyD to form inclusion complexes with fatty acids. For the W/O/W emulsion prepared with HP-β-CyD-ibuprofen, the highest encapsulation of ibuprofen was obtained at hyper- and iso-osmotic conditions and by using an excess molar ratio of CyD to ibuprofen. In the last part of the study, it was suggested that the chemical modification of the HP-β-CyD molecule did not influence the encapsulation of ibuprofen, as a similar encapsulation efficiency was obtained for an inclusion complex prepared with mono-1-glucose-β-CyD. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. [Long-term psychiatric hospitalizations].

    Science.gov (United States)

    Plancke, L; Amariei, A

    2017-02-01

    Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

  4. Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy

    DEFF Research Database (Denmark)

    Mauch, Peter; Ng, Andrea; Aleman, Berthe

    2005-01-01

    A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Ho...

  5. Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

    Directory of Open Access Journals (Sweden)

    Alejandro Hernández

    2008-01-01

    Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  6. Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

    Science.gov (United States)

    Hernández, Alejandro; Burgos, Héctor; Mondaca, Mauricio; Barra, Rafael; Núñez, Héctor; Pérez, Hernán; Soto-Moyano, Rubén; Sierralta, Walter; Fernández, Victor; Olivares, Ricardo; Valladares, Luis

    2008-01-01

    Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  7. Improving deformation models by discounting transient signals in geodetic data: 2. Geodetic data, stress directions, and long-term strain rates in Italy

    Science.gov (United States)

    Carafa, Michele M. C.; Bird, Peter

    2016-07-01

    The lithosphere of Italy is exposed to a number of different short-term strain transients, including but not limited to landslides, postseismic relaxation, and volcanic inflation/deflation. These transients affect GPS velocities and complicate the assessment of the long-term tectonic component of the surface deformation. In a companion paper we present a method for anticipating the principal patterns of nontectonic, short-term strains and building this information into the covariance matrix of the geodetic velocities. In this work we apply this method to Italian GPS velocities to build an augmented covariance matrix that characterizes all expected discrepancies between short- and long-term velocities. We find that formal uncertainties usually reported for GPS measurements are smaller than the variability of the same benchmarks across a geologic time span. Furthermore, we include in our modeling the azimuths of most compressive horizontal principal stresses (SHmax) because GPS data cannot resolve the active kinematics of coastal and offshore areas. We find that the final tectonic model can be made relatively insensitive to short-term interfering processes if the augmented covariance matrix and SHmax data records are used in the objective function. This results in a preferred neotectonic model that is also in closer agreement with independent geologic and seismological constraints and has the advantage of reducing short-term biases in forecasts of long-term seismicity.

  8. Recreational music-making: a cost-effective group interdisciplinary strategy for reducing burnout and improving mood states in long-term care workers.

    Science.gov (United States)

    Bittman, Barry; Bruhn, Karl T; Stevens, Christine; Westengard, James; Umbach, Paul O

    2003-01-01

    This controlled, prospective, randomized study examined the clinical and potential economic impact of a 6-session Recreational Music-making (RMM) protocol on burnout and mood dimensions, as well as on Total Mood Disturbance (TMD) in an interdisciplinary group of long-term care workers. A total of 112 employees participated in a 6-session RMM protocol focusing on building support, communication, and interdisciplinary respect utilizing group drumming and keyboard accompaniment. Changes in burnout and mood dimensions were assessed with the Maslach Burnout Inventory and the Profile of Mood States respectively. Cost savings were projected by an independent consulting firm, which developed an economic impact model. Statistically-significant reductions of multiple burnout and mood dimensions, as well as TMD scores, were noted. Economic-impact analysis projected cost savings of $89,100 for a single typical 100-bed facility, with total annual potential savings to the long-term care industry of $1.46 billion. A cost-effective, 6-session RMM protocol reduces burnout and mood dimensions, as well as TMD, in long-term care workers.

  9. Upward appraisal as a means for improving supervisory performance and promoting process improvement, with long-term implications for organizational change

    Science.gov (United States)

    Siegfeldt, Denise V.

    1994-01-01

    This study represents the implementation phase of an organizational development project which was initiated last year in the Management Support Division (MSD) at Langley Research Center to diagnose organizational functioning. As a result of MSD survey data from last year's effort, a Quality Action Team was created to address the responses compiled from the MSD Organizational Assessment Questionnaire and Follow-Up Questionnaire. The team was officially named the MSD Employee Relations Improvement Team (MERIT). MERIT's goal was to analyze major concerns generated by the questionnaires and to present feasible solutions to management which would improve supervisory performance, promote process improvement; and ultimately, lead to a better organization. The team met weekly and was very disciplined in following guidelines needed to ensure a fully functioning team. Several TQM tools were used during the team process, including brainstorming and the cause and effect diagram. One of the products produced by MERIT was a 'report card', more formally known as an upward appraisal system, to evaluate supervisory performance in the division office, its three branches, and in teams. Major areas of emphasis on the 47 item report card were those identified by employees through the previously administered questionnaires as needing to be improved; specifically, training, recognition, teamwork, supervision and leadership, and communication. MERIT created an enlarged and modified version of the report card which enabled scores for each individual supervisor to be recorded on a separate form, along with summary results and employee comments. Report card results have been compiled and fed back to the Division Chief and Assistant Division Chief. These individuals will in turn, feed the results back to the remaining supervisors and the team leaders. Although results differ among supervisors, some similarities exist. Communication generally appears to be adequate, which represents an

  10. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.

    Science.gov (United States)

    Liu, E; Tong, Y; Dotti, G; Shaim, H; Savoldo, B; Mukherjee, M; Orange, J; Wan, X; Lu, X; Reynolds, A; Gagea, M; Banerjee, P; Cai, R; Bdaiwi, M H; Basar, R; Muftuoglu, M; Li, L; Marin, D; Wierda, W; Keating, M; Champlin, R; Shpall, E; Rezvani, K

    2018-02-01

    Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.

  11. Effects of long-term theophylline exposure on recovery of respiratory function and expression of adenosine A1 mRNA in cervical spinal cord hemisected adult rats.

    Science.gov (United States)

    Nantwi, Kwaku D; Basura, Gregory J; Goshgarian, Harry G

    2003-07-01

    long as 30 days when drug administration was stopped and serum levels of the drug were virtually undetected. Furthermore, recovered activity in 3D and 7D animals increased significantly as a function of duration of weaning. Adenosine A1 receptor mRNA expression was not significantly changed by theophylline administration. It is concluded that recovery of respiratory function in C2-hemisected rats induced by chronic theophylline is unrelated to adenosine A1 receptor mRNA expression. Recovered activity persists even when drug administration has been stopped. The significance of our results is that in the clinical application of theophylline to improve respiratory impairment, intermittent drug administration may be sufficient to engender and maintain the therapeutic benefits of the drug.

  12. Simulating trends in crop yield and soil carbon in a long-term experiment - effects of rising CO2, N deposition and improved cultivation

    DEFF Research Database (Denmark)

    Berntsen, Jørgen; Petersen, Bjørn Molt; Olesen, Jørgen E.

    2006-01-01

    Measurements of crop yield and soil carbon in the Bad Lauchstädt long-term fertiliser experiment were analysed with the FASSET model. The model satisfactorily predicted yield and soil carbon development in four treatments: no fertiliser, mineral fertiliser, farmyard manure and farmyard manure plus...... was the use of new crop varieties and/or pesticides, while the increase in atmospheris CO2 and changes in local N deposition were of lesser importance. The rise in CO2 thus only explained 9-37% of the yield increase. The observed and simulated developments in soil carbon were quite different in the four...

  13. Chinese Herbal Medicines Might Improve the Long-Term Clinical Outcomes in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: Results of a Decision-Analytic Markov Model

    Directory of Open Access Journals (Sweden)

    Shao-Li Wang

    2015-01-01

    Full Text Available Aims. The priority of Chinese herbal medicines (CHMs plus conventional treatment over conventional treatment alone for acute coronary syndrome (ACS after percutaneous coronary intervention (PCI was documented in the 5C trial (chictr.org number: ChiCTR-TRC-07000021. The study was designed to evaluate the 10-year effectiveness of CHMs plus conventional treatment versus conventional treatment alone with decision-analytic model for ACS after PCI. Methods and Results. We constructed a decision-analytic Markov model to compare additional CHMs for 6 months plus conventional treatment versus conventional treatment alone for ACS patients after PCI. Sources of data came from 5C trial and published reports. Outcomes were expressed in terms of quality-adjusted life years (QALYs. Sensitivity analyses were performed to test the robustness of the model. The model predicted that over the 10-year horizon the survival probability was 77.49% in patients with CHMs plus conventional treatment versus 77.29% in patients with conventional treatment alone. In combination with conventional treatment, 6-month CHMs might be associated with a gained 0.20% survival probability and 0.111 accumulated QALYs, respectively. Conclusions. The model suggested that treatment with CHMs, as an adjunctive therapy, in combination with conventional treatment for 6 months might improve the long-term clinical outcome in ACS patients after PCI.

  14. The prediction of the level of personality organization on reduction of psychiatric symptoms and improvement of work ability in short- versus long-term psychotherapies during a 5-year follow-up.

    Science.gov (United States)

    Knekt, Paul; Lindfors, Olavi; Keinänen, Matti; Heinonen, Erkki; Virtala, Esa; Härkänen, Tommi

    2017-09-01

    How level of personality organization (LPO) predicts psychiatric symptoms and work ability in short- versus long-term psychotherapies is poorly known. We investigated the importance of the LPO on the benefits of short-term versus long-term psychotherapies. A cohort study based on 326 outpatients with mood or anxiety disorder was allocated to long-term (LPP) and short-term (SPP) psychodynamic psychotherapy, and solution-focused therapy (SFT). The LPO was assessed by interview at baseline and categorized into neuroses and higher level borderline. Outcome was assessed at baseline and 4-9 times during a 5-year follow-up, using self-report and interview-based measures of symptoms and work ability. For patients receiving SPP, improvement in work ability, symptom reduction, and the remission rate were more considerable in patients with neuroses than in higher level borderline patients, whereas LPP or SFT showed no notable differences in effectiveness in the two LPO groups. In patients with neuroses, improvement was more considerable in the short-term therapy groups during the first year of follow-up, and in higher level borderline patients LPP was more effective after 3 years of follow-up. The remission rate, defined as both symptom reduction and lack of auxiliary treatment, was higher in LPP than in SPP for both the LPO groups considered. In neuroses, short-term psychotherapy was associated with a more rapid reduction of symptoms and increase in work ability, whereas LPP was more effective for longer follow-ups in both LPO groups. Further large-scale studies are needed. Level of personality organization is relevant for selection between short- and long-term psychotherapies. Short-term therapy gives faster benefits for neurotic patients but not for patients with higher level borderline personality organization. Sustained remission from symptoms is more probable after long-term than short-term therapy. © 2016 The British Psychological Society.

  15. C-C4-02: Improving Survivorship Care for Long-Term Colorectal Cancer Survivors: Key Findings of a 5-Year Study

    Science.gov (United States)

    McMullen, Carmit K; Hornbrook, Mark C; Herrinton, Lisa J; Altschuler, Andrea; Grant, Marcia; Wendel, Christopher; Coons, Stephen Joel; Green, Sylvan B; Mohler, M Jane; Baldwin, Carol M; Ramirez, Michelle; Krouse, Robert S

    2010-01-01

    Aims: Understand the determinants of health related quality of life (HRQOL) and the lived experiences among colorectal cancer (CRC) survivors, and identify strategies to help maintain or enhance CRC survivors’ HRQOL. Methods: Mail survey and focus groups. Subjects were 283 ostomy and 392 anastomosis long-term CRC survivors within an HMO. Focus groups for subjects with ostomy were divided by gender and high and low HRQOL. Outcome measures were the modified City of Hope Quality of Life (mCOH-QOL)-Ostomy (abridged for anastomosis) and SF-36v2 questionnaires. The SF-6D scoring algorithm was used to calculate an overall HRQOL score from SF-36v2 data. Focus groups were conducted to explore ostomy-related barriers to effective self-care and adaptation strategies. Results: CRC survivors with an ostomy experienced multiple persistent HRQOL losses that differ between men and women. Women CRC survivors with ostomies, for example, reported more sleep disruption and fatigue than men. Living with an ostomy, co-morbidities, socioeconomic status, self-reported depression, and employment status were independent predictors of SF-6D scores. Among CRC survivors with ostomy, fistulas had important implications for HRQOL. Psychological wellbeing among CRC survivors was positively associated with income. Intestinal stomas significantly influenced spiritual HRQOL. Provision or withdrawal of a partners’ support affected both short- and long-term psychosocial adjustment of female CRC ostomy patients. Focus group participants identified dietary changes to control bowel output and odor, demands of coping and adjustment, and the time it took to accept the reality of daily living with an ostomy as significant challenges. Conclusions: The greatest challenges reported by CRC survivors confirmed the IOMs findings that survivorship is a distinct, chronic phase of cancer care, and that cancer effects are broad and pervasive. CRC survivors could benefit from dietary and behavioral interventions

  16. An Improved Methodology of Monetary Values of the Unit Collective Dose for Intervention Against Long-Term Exposure Following a Nuclear Accident

    International Nuclear Information System (INIS)

    Hwang, Won Tae; Kim, Eun Han; Suh, Kyung Suk; Choi, Young Gil; Han, Moon Hee

    2002-01-01

    A more practice approach for the determination of monetary values of the unit collective dose for intervention against long-term exposure following a nuclear accident was proposed. In addition, the monetary values of the unit collective dose estimated from the proposed approach were compared with those estimated from the previous model, which are derived from assumptions of routine exposure and the same values are applied in a nuclear accident without modification, using Korea economic data. The monetary values based on the proposed approach showed a distinct difference depending on inequity in the distribution of individual doses. The discounting rate was also an important factor in determination of monetary values of the unit collective dose

  17. An Improved Methodology of Monetary Values of the Unit Collective Dose for Intervention Against Long-Term Exposure Following a Nuclear Accident

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Won Tae; Kim, Eun Han; Suh, Kyung Suk; Choi, Young Gil; Han, Moon Hee [KAERI, Daejeon (Korea, Republic of)

    2002-06-15

    A more practice approach for the determination of monetary values of the unit collective dose for intervention against long-term exposure following a nuclear accident was proposed. In addition, the monetary values of the unit collective dose estimated from the proposed approach were compared with those estimated from the previous model, which are derived from assumptions of routine exposure and the same values are applied in a nuclear accident without modification, using Korea economic data. The monetary values based on the proposed approach showed a distinct difference depending on inequity in the distribution of individual doses. The discounting rate was also an important factor in determination of monetary values of the unit collective dose.

  18. Kootenai River Wildlife Habitat Enhancement Project : Long-term Bighorn Sheep/Mule Deer Winter and Spring Habitat Improvement Project : Wildlife Mitigation Project, Libby Dam, Montana : Management Plan.

    Energy Technology Data Exchange (ETDEWEB)

    Yde, Chis

    1990-06-01

    The Libby hydroelectric project, located on the Kootenai River in northwestern Montana, resulted in several impacts to the wildlife communities which occupied the habitats inundated by Lake Koocanusa. Montana Department of Fish, Wildlife and Parks, in cooperation with the other management agencies, developed an impact assessment and a wildlife and wildlife habitat mitigation plan for the Libby hydroelectric facility. In response to the mitigation plan, Bonneville Power Administration funded a cooperative project between the Kootenai National Forest and Montana Department of Fish, Wildlife and Parks to develop a long-term habitat enhancement plan for the bighorn sheep and mule deer winter and spring ranges adjacent to Lake Koocanusa. The project goal is to rehabilitate 3372 acres of bighorn sheep and 16,321 acres of mule deer winter and spring ranges on Kootenai National Forest lands adjacent to Lake Koocanusa and to monitor and evaluate the effects of implementing this habitat enhancement work. 2 refs.

  19. Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats

    Directory of Open Access Journals (Sweden)

    Alireza Sarkaki

    2013-09-01

    Full Text Available   Objective(s: Cerebral hypoperfusion/ischemia (CHI is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE on passive avoidance memory and long-term potentiation (LTP after permanent bilateral common carotid arteries occlusion (2CCAO in male adult rats.   Materials and Methods: Thirty-two adult male Wistar rats were randomly divided into: 1 Sham+Veh, 2 Isch+Veh, 3 Sham+GSE, 4 Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL was measured and LTP was recorded from hippocampal dentate gyrus (DG after high frequency stimulation (HFS in all rats. Results: We found that memory was significantly impaired in rats after CHI (P

  20. Improvement in switching characteristics and long-term stability of Zn-O-N thin-film transistors by silicon doping

    Directory of Open Access Journals (Sweden)

    Hiroshi Tsuji

    2017-06-01

    Full Text Available The effects of silicon doping on the properties of Zn-O-N (ZnON films and on the device characteristics of ZnON thin-film transistors (TFTs were investigated by co-sputtering silicon and zinc targets. Silicon doping was effective at decreasing the carrier concentration in ZnON films; therefore, the conductivity of the films can be controlled by the addition of a small amount of silicon. Doped silicon atoms also form bonds with nitrogen atoms, which suppresses nitrogen desorption from the films. Furthermore, Si-doped ZnON-TFTs are demonstrated to exhibit less negative threshold voltages, smaller subthreshold swings, and better long-term stability than non-doped ZnON-TFTs.

  1. Improved Long-Term Stability of Transparent Conducting Electrodes Based on Double-Laminated Electrosprayed Antimony Tin Oxides and Ag Nanowires

    Directory of Open Access Journals (Sweden)

    Koo B.-R.

    2017-06-01

    Full Text Available We fabricated double-laminated antimony tin oxide/Ag nanowire electrodes by spin-coating and electrospraying. Compared to pure Ag nanowire electrodes and single-laminated antimony tin oxide/Ag nanowire electrodes, the double-laminated antimony tin oxide/Ag nanowire electrodes had superior transparent conducting electrode performances with sheet resistance ~19.8 Ω/□ and optical transmittance ~81.9%; this was due to uniform distribution of the connected Ag nanowires because of double lamination of the metallic Ag nanowires without Ag aggregation despite subsequent microwave heating at 250°C. They also exhibited excellent and superior long-term chemical and thermal stabilities and adhesion to substrate because double-laminated antimony tin oxide thin films act as the protective layers between Ag nanowires, blocking Ag atoms penetration.

  2. Nuclear Energy, Long Term Requirements

    International Nuclear Information System (INIS)

    Knapp, V.

    2006-01-01

    There are serious warnings about depletion of oil and gas and even more serious warnings about dangers of climate change caused by emission of carbon dioxide. Should developed countries be called to replace CO2 emitting energy sources as soon as possible, and the time available may not be longer then few decades, can nuclear energy answer the call and what are the requirements? Assuming optimistic contribution of renewable energy sources, can nuclear energy expand to several times present level in order to replace large part of fossil fuels use? Paper considers intermediate and long-term requirements. Future of nuclear power depends on satisfactory answers on several questions. First group of questions are those important for near and intermediate future. They deal with economics and safety of nuclear power stations in the first place. On the same time scale a generally accepted concept for radioactive waste disposal is also required. All these issues are in the focus of present research and development. Safer and more economical reactors are targets of international efforts in Generation IV and INPRO projects, but aiming further ahead these innovative projects are also addressing issues such as waste reduction and proliferation resistance. However, even assuming successful technical development of these projects, and there is no reason to doubt it, long term and large-scale nuclear power use is thereby not yet secured. If nuclear power is to play an essential role in the long-term future energy production and in reduction of CO2 emission, than several additional questions must be replied. These questions will deal with long-term nuclear fuel sufficiency, with necessary contribution of nuclear power in sectors of transport and industrial processes and with nuclear proliferation safety. This last issue is more political then technical, thus sometimes neglected by nuclear engineers, yet it will have essential role for the long-term prospects of nuclear power. The

  3. Early crisis nontechnical skill teaching in residency leads to long-term skill retention and improved performance during crises: A prospective, nonrandomized controlled study.

    Science.gov (United States)

    Doumouras, Aristithes G; Engels, Paul T

    2017-07-01

    Medical error is common in crises, and the majority of observed errors are nontechnical in nature. The long-term impact of teaching crisis nontechnical skills to residents has not been evaluated. The objective of this study was to determine the effect of simulation-based teaching of crisis nontechnical skills compared to controls one year after initial teaching. This was a prospective study using both historical controls and a before-and-after methodology to evaluate the effect of a high-fidelity simulation curriculum that used crisis resource management principles to teach nontechnical skills. Postgraduate year 2 and 3 residents were invited to take part in a prospective training course over 2 years. The primary outcome was leader performance evaluated by expert raters using the previously validated 7-point Ottawa Global Rating Scale. Overall, 23 residents performed 30 simulations over the 2 years with the intervention group of 7 residents being assessed in both years. After adjustment, the postgraduate year 3 intervention group who received training the previous year had significantly higher overall performance scores than all postgraduate year 2 scores (1.09 95% confidence interval 0.70-1.47, P crisis performance compared to historical postgraduate year 3 controls and untrained postgraduate year 2 residents. There were no significant differences between the crisis performance of postgraduate year 2 residents and the untrained postgraduate year 3 controls. This confirms the beneficial effect and long-term retention after crisis nontechnical skill training. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Intermediate-term and long-term outcome of piggyback drainage: connecting glaucoma drainage device to a device in-situ for improved intraocular pressure control.

    Science.gov (United States)

    Dervan, Edward; Lee, Edward; Giubilato, Antonio; Khanam, Tina; Maghsoudlou, Panayiotis; Morgan, William H

    2017-11-01

    This study provides results of a treatment option for patients with failed primary glaucoma drainage device. The study aimed to describe and evaluate the long-term intraocular pressure control and complications of a new technique joining a second glaucoma drainage device directly to an existing glaucoma drainage device termed 'piggyback drainage'. This is a retrospective, interventional cohort study. Eighteen eyes of 17 patients who underwent piggyback drainage between 2004 and 2013 inclusive have been studied. All patients had prior glaucoma drainage device with uncontrolled intraocular pressure. The piggyback technique involved suturing a Baerveldt (250 or 350 mm) or Molteno3 glaucoma drainage device to an unused scleral quadrant and connecting the silicone tube to the primary plate bleb. Failure of intraocular pressure control defined as an intraocular pressure greater than 21 mmHg on maximal therapy on two separate occasions or further intervention to control intraocular pressure. The intraocular pressure was controlled in seven eyes (39%) at last follow-up with a mean follow-up time of 74.2 months. The mean preoperative intraocular pressure was 27.1 mmHg (95% confidence interval 23.8-30.3) compared with 18.4 mmHg (95% confidence interval 13.9-22.8) at last follow-up. The mean time to failure was 57.1 months (95% confidence interval 32.2-82), and the mean time to further surgery was 72.3 months (95% confidence interval 49.9-94.7). Lower preoperative intraocular pressure was associated with longer duration of intraocular pressure control (P = 0.048). If the intraocular pressure was controlled over 2 years, it continued to be controlled over the long term. Two eyes (11%) experienced corneal decompensation. Piggyback drainage represents a viable surgical alternative for the treatment of patients with severe glaucoma with failing primary glaucoma drainage device, particularly in those at high risk of corneal decompensation. © 2017 Royal Australian and New Zealand

  5. Minimally Invasive Placement of Spinal Cord Stimulator Paddle Electrodes Is Associated With Improved Perioperative and Long-Term Experience Among Neuropathic Pain Patients.

    Science.gov (United States)

    Shamji, Mohammed F; Paul, Darcia; Mednikov, Alina

    2018-03-01

    Prospective, observational cohort study. This study compared in-hospital and long-term outcomes among spinal cord stimulation (SCS) patients undergoing paddle insertion by open or minimally invasive surgery (MIS) approaches. Patients with treatment-refractory extremity neuropathic pain may benefit from SCS. Conventional placement of surgical paddles for an external neurostimulation trial is through open laminectomy, but MIS techniques may offer advantages. Twenty SCS patients were prospectively assessed. Open patients underwent caudal thoracic laminectomy for multicolumnar electrode paddle placement. MIS patients underwent paddle placement through interlaminar flavectomy using tubular retractors. Demographic data included age, sex, underlying diagnosis, and preoperative visual analog scale (VAS) extremity scores. Intraoperative data included operative duration, blood loss, and number of device passages to achieve final position. Perioperative data included VAS back pain scores; trial data included time-to-trial and time-to-decision. Postoperative data included 1 month VAS back pain scores and 1 year follow-up device complications. No demographic differences were observed among surgical cohorts. MIS procedures had shorter operative duration (P = 0.03), less blood loss (P patients reported less perioperative surgical back pain (P patients who also made sooner decision whether to implant the SCS device (2.8 ± 1.4 vs 4.3 ± 1.0 days, P = 0.013). Similar 1 month back pain scores were reported between surgical cohorts (P = 0.08). MIS techniques for SCS surgical paddle implantation is associated with less perioperative morbidity and surgical site back pain, shorter external neurostimulator trial duration, and long-term device stability benefits. 2.

  6. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    Science.gov (United States)

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Kollins, S.H.; Wigal, T.L.; Newcorn, J.H.; Telang, F.W.; Fowler, J.S.; Logan, J.; Wong, C.T.; Swanson, J.M.

    2012-01-01

    Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and ( 11 C)raclopride (D 2 /D 3 receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D 2 /D 3 receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

  8. Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Wang G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Kollins, S.H.; Wigal, T.L.; Newcorn, J.H.; Telang, F.W.; Fowler, J.S.; Logan, J.; Wong, C.T.; Swanson, J.M.

    2012-01-18

    Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [{sup 11}C]raclopride (D{sub 2}/D{sub 3} receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D{sub 2}/D{sub 3} receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

  9. Analysing long term discursive processes

    DEFF Research Database (Denmark)

    Horsbøl, Anders

    which extend beyond the single interaction, for instance negotiations or planning processes, seems to have played a less important role, with studies such as Iedema 2001 and Wodak 2000 as exceptions. These long term processes, however, are central to the constitution and workings of organizations......What do timescales - the notion that processes take place or can be viewed within a shorter or longer temporal range (Lemke 2005) - mean for the analysis of discourse? What are the methodological consequences of analyzing discourse at different timescales? It may be argued that discourse analysis...... in general has favored either the analysis of short term processes such as interviews, discussions, and lessons, or the analysis of non-processual entities such as (multimodal) texts, arguments, discursive repertoires, and discourses (in a Foucaultian sense). In contrast, analysis of long term processes...

  10. Comparing long term energy scenarios

    International Nuclear Information System (INIS)

    Cumo, M.; Simbolotti, G.

    2001-01-01

    Major projection studies by international organizations and senior analysts have been compared with reference to individual key parameters (population, energy demand/supply, resources, technology, emissions and global warming) to understand trends and implications of the different scenarios. Then, looking at the long term (i.e., 2050 and beyond), parameters and trends have been compared together to understand and quantify whether and when possible crisis or market turbulence might occur due to shortage of resources or environmental problems [it

  11. Long term radioactive waste management

    International Nuclear Information System (INIS)

    Lavie, J.M.

    1984-01-01

    In France, waste management, a sensitive issue in term of public opinion, is developing quickly, and due to twenty years of experience, is now reaching maturity. With the launching of the French nuclear programme, the use of radioactive sources in radiotherapy and industry, waste management has become an industrial activity. Waste management is an integrated system dealing with the wastes from their production to the long term disposal, including their identification, sortage, treatment, packaging, collection and transport. This system aims at guaranteing the protection of present and future populations with an available technology. In regard to their long term management, and the design of disposals, radioactive wastes are divided in three categories. This classification takes into account the different radioisotopes contained, their half life and their total activity. Presently short-lived wastes are stored in the shallowland disposal of the ''Centre de la Manche''. Set up within the French Atomic Energy Commission (CEA), the National Agency for waste management (ANDRA) is responsible within the framework of legislative and regulatory provisions for long term waste management in France [fr

  12. Accounting of Long-Term Biological Assets

    OpenAIRE

    Valeriy Mossakovskyy; Vasyl Korytnyy

    2015-01-01

    The article is devoted to generalization of experience in valuation of long-term biological assets of plant-growing and animal-breeding, and preparation of suggestions concerning improvement of accounting in this field. Recommendations concerning accounting of such assets are given based on the study of accounting practice at specific agricultural company during long period of time. Authors believe that fair value is applicable only if price level for agricultural products is fixed by the gov...

  13. Long term expression of Drosophila melanogaster nucleoside kinase in thymidine kinase 2-deficient mice with no lethal effects caused by nucleotide pool imbalances.

    Science.gov (United States)

    Krishnan, Shuba; Paredes, João A; Zhou, Xiaoshan; Kuiper, Raoul V; Hultenby, Kjell; Curbo, Sophie; Karlsson, Anna

    2014-11-21

    Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2(-/-)) mice extended the life span of Tk2(-/-) mice from 3 weeks to at least 20 months. The Dm-dNK(+/-)Tk2(-/-) mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK(+/-)Tk2(-/-) mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK(+/-) mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Influence of bone morphogenetic protein-2 on the extracellular matrix, material properties, and gene expression of long-term articular chondrocyte cultures: loss of chondrocyte stability.

    Science.gov (United States)

    Krawczak, David A; Westendorf, Jennifer J; Carlson, Cathy S; Lewis, Jack L

    2009-06-01

    The aim of this study was to determine the effects of bone morphogenetic protein-2 (BMP-2) on articular chondrocyte tissues grown as monolayers in vitro for up to 8 weeks. Articular chondrocytes were isolated from New Zealand White rabbits and plated in monolayer cultures. The cultures were supplemented with 100 ng/mL of BMP-2 for up to 8 weeks and the extracellular matrix (ECM) composition, material properties, and messenger RNA (mRNA) expression were analyzed. mRNA expression of cartilage-specific genes, type II collagen, and aggrecan showed that BMP-2 enhanced chondrocyte stability for up to 3 weeks. After 3 weeks in culture, there was substantially more type I collagen expression and more osteopontin and runt-related transcription factor 2 expression in 5- and 8-week cultures treated with BMP-2 than in controls. Additionally, matrix metalloproteinase-13 and ADAMTS-5 (A disintegrin-like and metalloproteinase with thrombospondin 5) were upregulated in 5- and 8-week cultures treated with BMP-2, coinciding with a loss of ECM density, collagen, and proteoglycan. Eight-week tissue stimulated with BMP-2 was more fragile and tore more easily when removed from the culture dish as compared to controls, suggesting temporal limitations to the effectiveness of BMP-2 in monolayer systems and perhaps other models to enhance the generation of a cartilage-like tissue for tissue engineering purposes.

  15. Changes in Histopathology, Enzyme Activities, and the Expression of Relevant Genes in Zebrafish (Danio rerio) Following Long-Term Exposure to Environmental Levels of Thallium.

    Science.gov (United States)

    Hou, Li-Ping; Yang, Yang; Shu, Hu; Ying, Guang-Guo; Zhao, Jian-Liang; Chen, Yi-Bing; Chen, Yong-Heng; Fang, Gui-Zhen; Li, Xin; Liu, Ji-Sheng

    2017-11-01

    Thallium is a rare-earth element, but widely distributed in water environments, posing a potential risk to our health. This study was designed to investigate the chronic effects of thallium based on physiological responses, gene expression, and changes in the activity of relevant enzymes in adult zebra fish exposed to thallium at low doses. The endpoints assessed include mRNA expression of metallothionein (MT)2 and heat shock protein HSP70; enzymatic activities of superoxide dismutase (SOD) and Na + /K + -ATPase; and the histopathology of gill, gonad, and liver tissues. The results showed significant increases in HSP70 mRNA expression following exposure to 100 ng/L thallium and in MT2 expression following exposure to 500 ng/L thallium. Significantly higher activities were observed for SOD in liver and Na + /K + -ATPase activity in gill in zebra fish exposed to thallium (20 and 100 ng/L, respectively) in comparison to control fish. Gill, liver, and gonad tissues displayed different degrees of damage. The overall results imply that thallium may cause toxicity to zebra fish at environmentally relevant aqueous concentrations.

  16. On the very long term delayed behavior of concrete

    International Nuclear Information System (INIS)

    Torrenti, J.M.; Benboudjema, F.; Barre, F.; Gallitre, E.

    2015-01-01

    The prediction of very long-term deformation of prestressed concrete structures is a major challenge considering the service life of these structures. It is therefore necessary to correctly model the delayed behavior of these structures. Using a review of laboratory tests and observations of the delayed behavior of structures (bridges and nuclear power plants), the main conclusions of this work are the following ones. First, very long term creep in laboratory or of real structures seems to be non asymptotic. In the actual Eurocode-2, creep is calculated by means of an asymptotic hyperbolic function while in the recent Model Code 2010 creep is expressed as a combination of an asymptotic and a logarithmic functions. In the latter case the logarithmic function corresponds to basic creep while drying creep is asymptotic. Secondly, using a long test (3 years) in a laboratory is not enough to assess the long term behaviour of a massive structure. We need physical relations for creep in codes in order to predict the delayed behavior of massive structures. Thirdly, the biaxial creep of nuclear power plant could be modelled but using data of the structure itself. This would allow to predict the delayed behavior of these structures. Further work is needed to improve the prediction in the design phase

  17. Long-term intake of a high prebiotic fiber diet but not high protein reduces metabolic risk after a high fat challenge and uniquely alters gut microbiota and hepatic gene expression.

    Science.gov (United States)

    Saha, Dolan C; Reimer, Raylene A

    2014-09-01

    A mismatch between early developmental diet and adulthood may increase obesity risk. Our objective was to determine the effects of re-matching rats to their weaning diets high in protein or fiber after transient high-fat/high-sucrose challenge in adulthood. We hypothesize that a long-term high fiber diet will be associated with a gut microbiota and hepatic gene expression reflective of reduced adiposity. Wistar rat pups were fed a control (C), high prebiotic fiber (HF), or high protein (HP) diet from 3-15 weeks of age; a high-fat/high-sucrose diet from 15-21 weeks; their respective C, HF, or HP diets from 21-25 weeks. Gut microbiota of cecal contents and hepatic gene expression were measured when rats were terminated at 25 weeks of age. HF rats had higher total bacteria, bifidobacteria and Bacteroides/Prevotella spp than C and HP at 25 weeks (P diet attenuated the typical increase in Firmicutes:Bacteroidetes ratio associated with consumption of a high fat diet. Lower hepatic cholesterol with long-term HF diet intake may be related to alterations in gut microbiota and hepatic lipid metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Unified pre- and postsynaptic long-term plasticity enables reliable and flexible learning.

    Science.gov (United States)

    Costa, Rui Ponte; Froemke, Robert C; Sjöström, P Jesper; van Rossum, Mark Cw

    2015-08-26

    Although it is well known that long-term synaptic plasticity can be expressed both pre- and postsynaptically, the functional consequences of this arrangement have remained elusive. We show that spike-timing-dependent plasticity with both pre- and postsynaptic expression develops receptive fields with reduced variability and improved discriminability compared to postsynaptic plasticity alone. These long-term modifications in receptive field statistics match recent sensory perception experiments. Moreover, learning with this form of plasticity leaves a hidden postsynaptic memory trace that enables fast relearning of previously stored information, providing a cellular substrate for memory savings. Our results reveal essential roles for presynaptic plasticity that are missed when only postsynaptic expression of long-term plasticity is considered, and suggest an experience-dependent distribution of pre- and postsynaptic strength changes.

  19. Long Term Expression of Drosophila melanogaster Nucleoside Kinase in Thymidine Kinase 2-deficient Mice with No Lethal Effects Caused by Nucleotide Pool Imbalances*

    Science.gov (United States)

    Krishnan, Shuba; Paredes, João A.; Zhou, Xiaoshan; Kuiper, Raoul V.; Hultenby, Kjell; Curbo, Sophie; Karlsson, Anna

    2014-01-01

    Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2−/−) mice extended the life span of Tk2−/− mice from 3 weeks to at least 20 months. The Dm-dNK+/−Tk2−/− mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK+/−Tk2−/− mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK+/− mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues. PMID:25296759

  20. AHR over-expression in papillary thyroid carcinoma: clinical and molecular assessments in a series of Italian acromegalic patients with a long-term follow-up.

    Directory of Open Access Journals (Sweden)

    Caterina Mian

    Full Text Available Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3-7%. Germline mutations in the aryl-hydrocarbon receptor (AHR interacting protein (AIP have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer.Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied.12 DTCs (10 papillary and 2 follicular carcinomas were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status.The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma.

  1. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    International Nuclear Information System (INIS)

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-01-01

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life

  2. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  3. Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody.

    Science.gov (United States)

    Piperno, G M; López-Requena, A; Predonzani, A; Dorvignit, D; Labrada, M; Zentilin, L; Burrone, O R; Cesco-Gaspere, M

    2015-12-01

    The ganglioside GM3(Neu5Gc) has gained increasing attention as therapeutic target because of its selective expression in various human tumours, such as melanoma, breast and lung cancer. 14F7 is a mouse IgG1 with specific reactivity to GM3(Neu5Gc)-positive tumours. The therapeutic activity of 14F7 has also been demonstrated in vivo, through its repetitive passive administration in tumour-bearing animals. In this work we used an alternative strategy to deliver recombinant 14F7 in vivo and analysed the therapeutic efficacy of this approach. We engineered a recombinant adeno-associated vector to direct the expression of secretable recombinant 14F7 in BALB/c animals. A single administration of the rAAV induced efficient production and secretion of the antibody in the bloodstream, with an expression level reaching plateau at ∼3 weeks after injection and persisting for almost a year. Strikingly, upon challenge with GM3(Neu5Gc)-positive X63-AG8.653 myeloma cells, tumour development was significantly delayed in animals treated with rAAV-14F7 with respect to animals treated with a control rAAV codifying for an irrelevant antibody. Finally, no significant differences in survival proportion were detected in animals injected with rAAV-14F7 or treated by standard administration of repetitive doses of purified monoclonal antibody 14F7.

  4. Targeted inhibition of TGF-β results in an initial improvement but long-term deficit in force production after contraction-induced skeletal muscle injury.

    Science.gov (United States)

    Gumucio, Jonathan P; Flood, Michael D; Phan, Anthony C; Brooks, Susan V; Mendias, Christopher L

    2013-08-15

    Transforming growth factor-β (TGF-β) is a proinflammatory cytokine that regulates the response of many tissues following injury. Previous studies in our lab have shown that treating muscles with TGF-β results in a dramatic accumulation of type I collagen, substantial fiber atrophy, and a marked decrease in force production. Because TGF-β promotes atrophy and fibrosis, our objective was to investigate whether the inhibition of TGF-β after injury would enhance the recovery of muscle following injury. We hypothesized that inhibiting TGF-β after contraction-induced injury would improve the functional recovery of muscles by preventing muscle fiber atrophy and weakness, and by limiting the accumulation of fibrotic scar tissue. To test this hypothesis, we induced an injury using a series of in situ lengthening contractions to extensor digitorum longus muscles of mice treated with either a bioneutralizing antibody against TGF-β or a sham antibody. Compared with controls, muscles from mice receiving TGF-β inhibitor showed a greater recovery in force 3 days and 7 days after injury but had a decrease in force compared with controls at the 21-day time point. The early enhancement in force in the TGF-β inhibitor group was associated with an initial improvement in tissue morphology, but, at 21 days, while the control group was fully recovered, the TGF-β inhibitor group displayed an irregular extracellular matrix and an increase in atrogin-1 gene expression. These results indicate that the inhibition of TGF-β promotes the early recovery of muscle function but is detrimental overall to full muscle recovery following moderate to severe muscle injuries.

  5. Modulation of innate immunity and gene expressions in white shrimp Litopenaeus vannamei following long-term starvation and re-feeding

    Science.gov (United States)

    Lin, Yong-Chin; Chen, Jiann-Chu; C. Man, Siti Nursafura; W. Morni, Wan Zabidii; N.A. Suhaili, Awangku Shahrir; Cheng, Sha-Yen; Hsu, Chih-Hung

    2012-01-01

    The survival rate, weight loss, immune parameters, resistance against Vibrio alginolyticus and white-spot syndrome virus (WSSV), and expressions of lipopolysaccharide- and ß-glucan-binding protein (LGBP), peroxinectin (PX), prophenoloxidase-activating enzyme (ppA), prophenoloxidase (proPO) I, proPO II, α2-macroglobulin (α2-M), integrin ß, heat shock protein 70 (HSP70), cytosolic manganese superoxide dismutase (cytMnSOD), mitochondrial manganese superoxide dismutase (mtMnSOD), and extracellular copper and zinc superoxide dismutase (ecCuZnSOD) were examined in the white shrimp Litopenaeus vannamei (8.18 ± 0.86 g body weight) which had been denied food (starved) for up to 14–28 days. Among shrimp which had been starved for 7, 14, 21, and 28 days, 100%, 90%, 71%, and 59% survived, and they lost 3.2%, 7.3%, 9.2%, and 10.4% of their body weight, respectively. Hyaline cells (HCs), granular cells (GCs, including semi-granular cells), the total haemocyte count (THC), phenoloxidase (PO) activity, respiratory bursts (RBs), and SOD activity significantly decreased in shrimp which had been starved for 1, 1, 1, 5, 14, and 3 days, respectively. The expression of integrin ß significantly decreased after 0.5–5 days of starvation, whereas the expressions of LGBP, PX, proPO I, proPO II, ppA, and α2-M increased after 0.5–1 days. Transcripts of all genes except ecCuZnSOD decreased to the lowest level after 5 days, and tended to background values after 7 and 14 days. Cumulative mortality rates of 7-day-starved shrimp challenged with V. alginolyticus and WSSV were significantly higher than those of challenged control-shrimp for 1–7 and 1–4 days, respectively. In another experiment, immune parameters of shrimp which had been starved for 7 and 14 days and then received normal feeding (at 5% of their body weight daily) were examined after 3, 6, and 12 h, and 1, 3, and 5 days. All immune parameters of 7-day-starved shrimp were able to return to their baseline values

  6. Murine model of long term obstructive jaundice

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A.; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-01-01

    Background With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of 3 murine models of obstructive jaundice. Methods C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Results 70% (7/10) of tCL mice died by Day 7, whereas majority 67% (10/15) of pCL mice survived with loss of jaundice. 19% (3/16) of LMHL mice died; however, jaundice continued beyond Day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 days after ligation but jaundice rapidly decreased by Day 7. The LHML group developed portal hypertension as well as severe fibrosis by Day 14 in addition to prolonged jaundice. Conclusion The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice but long term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. PMID:27916350

  7. A new image for long-term care.

    Science.gov (United States)

    Wager, Richard; Creelman, William

    2004-04-01

    To counter widely held negative images of long-term care, managers in the industry should implement quality-improvement initiatives that include six key strategies: Manage the expectations of residents and their families. Address customers' concerns early. Build long-term customer satisfaction. Allocate resources to achieve exceptional outcomes in key areas. Respond to adverse events with compassion. Reinforce the facility's credibility.

  8. Effects of Long-Term Exposure to 60 GHz Millimeter-Wavelength Radiation on the Genotoxicity and Heat Shock Protein (Hsp Expression of Cells Derived from Human Eye

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