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  1. Impairment of Cellulose Synthases Required for Arabidopsis Secondary Cell Wall Formation Enhances Disease Resistance[W

    Science.gov (United States)

    Hernández-Blanco, Camilo; Feng, Dong Xin; Hu, Jian; Sánchez-Vallet, Andrea; Deslandes, Laurent; Llorente, Francisco; Berrocal-Lobo, Marta; Keller, Harald; Barlet, Xavier; Sánchez-Rodríguez, Clara; Anderson, Lisa K.; Somerville, Shauna; Marco, Yves; Molina, Antonio

    2007-01-01

    Cellulose is synthesized by cellulose synthases (CESAs) contained in plasma membrane–localized complexes. In Arabidopsis thaliana, three types of CESA subunits (CESA4/IRREGULAR XYLEM5 [IRX5], CESA7/IRX3, and CESA8/IRX1) are required for secondary cell wall formation. We report that mutations in these proteins conferred enhanced resistance to the soil-borne bacterium Ralstonia solanacearum and the necrotrophic fungus Plectosphaerella cucumerina. By contrast, susceptibility to these pathogens was not altered in cell wall mutants of primary wall CESA subunits (CESA1, CESA3/ISOXABEN RESISTANT1 [IXR1], and CESA6/IXR2) or POWDERY MILDEW–RESISTANT5 (PMR5) and PMR6 genes. Double mutants indicated that irx-mediated resistance was independent of salicylic acid, ethylene, and jasmonate signaling. Comparative transcriptomic analyses identified a set of common irx upregulated genes, including a number of abscisic acid (ABA)–responsive, defense-related genes encoding antibiotic peptides and enzymes involved in the synthesis and activation of antimicrobial secondary metabolites. These data as well as the increased susceptibility of ABA mutants (abi1-1, abi2-1, and aba1-6) to R. solanacearum support a direct role of ABA in resistance to this pathogen. Our results also indicate that alteration of secondary cell wall integrity by inhibiting cellulose synthesis leads to specific activation of novel defense pathways that contribute to the generation of an antimicrobial-enriched environment hostile to pathogens. PMID:17351116

  2. Enhancing disease surveillance reporting using public transport in ...

    African Journals Online (AJOL)

    Enhancing disease surveillance reporting using public transport in Dodoma District, Central Tanzania. ... LEG Mboera, SF Rumisha, EJ Mwanemile, E Mziwanda, PK Mmbuji ... Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  3. Contrast enhanced MRI in Hirayama disease

    International Nuclear Information System (INIS)

    Penev, L.; Georgieva-Kosarova, G.

    2015-01-01

    Full text: HD is a very rare condition characterized by asymmetric distal upper limbs muscle weakness and atrophy in the C8-T1 distribution without sensory or pyramidal signs. Classically, adolescent males develop initially progressive weakness followed by spontaneous stabilization within several years after onset. The pathogenesis of the disease is unclear and pathologic studies are lacking. However the prevailing theory postulates that insufficient growth of the dura relative to the spinal column during puberty allows forward displacement of the dura in flexion with compression of the spinal cord, possibly leading to ischemia of the anterior horn cells at C8 and Th1. Most reported cases have been from Asia, particularly Japan, though some have been reported from India, the Middle East, and Europe. To date, and to our knowledge, there has been no published study characterizing the MR imaging features of this disease in Bulgaria. Routine MR imaging of patients with HD has shown segmental cord atrophy, rarely associated with Th2 abnormalities. Previous studies of other cord diseases have shown, that the extent of cord tissue damage is usually underestimated by using routine MR imaging and that brain plasticity might limit the clinical consequences of cord injury. In this study, we used a multiparametric MR imaging approach to investigate in a patient with HD

  4. Enhancing radiotherapeutic efficiency in thyroid diseases

    International Nuclear Information System (INIS)

    Afanas'eva, N.I.; Filatov, A.A.

    1989-01-01

    Scientifically substantiated figures of material costs spent on the main types of radiotherapy of thyroid diseases were calculated. Cost calculation was based on the principle of the use of means in the nonindustrial field of economy. The cost of each investigation was calculated as full expenses (main funds and current costs) allocated for a particular type of investigation in any arbitrary period of time, divided into the number of investigations performed over this period. Standardization of investigations taking account of the elaborated tactical schemes makes it possible to decrease notably (almost by 20%) material cost on the investigation of thyroid patients

  5. Limits to human enhancement: nature, disease, therapy or betterment?

    Science.gov (United States)

    Hofmann, Bjørn

    2017-10-10

    New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

  6. Contrast-enhanced Ultrasound for Non-tumor Liver Diseases

    Directory of Open Access Journals (Sweden)

    H Maruyama

    2012-03-01

    Full Text Available Contrast-enhanced ultrasound (CEUS is a simple, safe and reliable technique for the clinical management of patients with various liver diseases. Although the major target of the technique may be focal hepatic lesions, it is also effective for the diagnosis of non-tumor liver diseases, such as grading hepatic fibrosis, characterization of chronic liver diseases and diagnosis of portal vein thrombosis. This review article aimed to overview the recent application of CEUS in the assessment of non-tumor liver diseases. Keywords: Cirrhosis, contrast agent, fibrosis, idiopathic portal hypertension, microbubble, portal vein thrombosis, ultrasound.

  7. Gadolinium-enhanced MR angiography of the thoracoabdominal aorta diseases

    International Nuclear Information System (INIS)

    D'Ippolito, Giuseppe; Wolosker, Nelson; Galvao Filho, Mario; Kalil, Jorge A.; Wolosker, Angela; Borri, Maria Lucia

    1998-01-01

    Gadolinium-enhanced MR angiography (GEMRA) of the thoracoabdominal aorta is a noninvasive technique that can rapidly delineate the branch vessels diseases, without flow or respiration artifacts, obtained with non contrast MRA. The objective of this paper is to show the main clinical applications of GEMRA, compared to non contrast sequences. We have evaluated 30 patients with thorocoabdominal aorta diseases. These patients have been examined with GEMRA (3D, FFE sequences) obtained after 30 mlIV contrast injection and non contrast MRA (2D-TOF sequences). In our experience, gadolinium-enhanced MRA is a high resolution and speedy technique with advantages over non contrast MRA. (author)

  8. Medications Used for Cognitive Enhancement in Patients With Schizophrenia, Bipolar Disorder, Alzheimer's Disease, and Parkinson's Disease.

    Science.gov (United States)

    Hsu, Wen-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2018-01-01

    Cognitive impairment, which frequently occurs in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease, has a significant impact on the daily lives of both patients and their family. Furthermore, since the medications used for cognitive enhancement have limited efficacy, the issue of cognitive enhancement still remains a clinically unsolved challenge. We reviewed the clinical studies (published between 2007 and 2017) that focused on the efficacy of medications used for enhancing cognition in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease. Acetylcholinesterase inhibitors and memantine are the standard treatments for Alzheimer's disease and Parkinson's disease. Some studies have reported selective cognitive improvement in patients with schizophrenia following galantamine treatment. Newer antipsychotics, including paliperidone, lurasidone, aripiprazole, ziprasidone, and BL-1020, have also been reported to exert cognitive benefits in patients with schizophrenia. Dopaminergic medications were found to improve language function in patients with Parkinson's disease. However, no beneficial effects on cognitive function were observed with dopamine agonists in patients with schizophrenia. The efficacies of nicotine and its receptor modulators in cognitive improvement remain controversial, with the majority of studies showing that varenicline significantly improved the cognitive function in schizophrenic patients. Several studies have reported that N -methyl-d-aspartate glutamate receptor (NMDAR) enhancers improved the cognitive function in patients with chronic schizophrenia. NMDAR enhancers might also have cognitive benefits in patients with Alzheimer's disease or Parkinson's disease. Raloxifene, a selective estrogen receptor modulator, has also been demonstrated to have beneficial effects on attention, processing speed, and memory in female patients with schizophrenia. Clinical trials with

  9. Music Enhances Autobiographical Memory in Mild Alzheimer's Disease

    Science.gov (United States)

    El Haj, Mohamad; Postal, Virginie; Allain, Philippe

    2012-01-01

    Studies have shown that the "Four Seasons" music may enhance the autobiographical performance of Alzheimer's disease (AD) patients. We used a repeated measures design in which autobiographical recall of 12 mild AD patients was assessed using a free narrative method under three conditions: (a) in "Silence," (b) after being exposed to the opus "Four…

  10. Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

    Science.gov (United States)

    Halstead, Scott B

    2017-11-07

    During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection. The corresponding age specific hospitalization curve for placebos experiencing heterotypic secondary dengue infections peaked at age, 9-11 years. These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Contrast-enhanced endoscopic ultrasonography in digestive diseases.

    Science.gov (United States)

    Hirooka, Yoshiki; Itoh, Akihiro; Kawashima, Hiroki; Ohno, Eizaburo; Itoh, Yuya; Nakamura, Yosuke; Hiramatsu, Takeshi; Sugimoto, Hiroyuki; Sumi, Hajime; Hayashi, Daijiro; Ohmiya, Naoki; Miyahara, Ryoji; Nakamura, Masanao; Funasaka, Kohei; Ishigami, Masatoshi; Katano, Yoshiaki; Goto, Hidemi

    2012-10-01

    Contrast-enhanced endoscopic ultrasonography (CE-EUS) was introduced in the early 1990s. The concept of the injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) led to "endoscopic ultrasonographic angiography". After the arrival of the first-generation contrast agent, high-frequency (12 MHz) EUS brought about the enhancement of EUS images in the diagnosis of pancreatico-biliary diseases, upper gastrointestinal (GI) cancer, and submucosal tumors. The electronic scanning endosonoscope with both radial and linear probes enabled the use of high-end ultrasound machines and depicted the enhancement of both color/power Doppler flow-based imaging and harmonic-based imaging using second-generation contrast agents. Many reports have described the usefulness of the differential diagnosis of pancreatic diseases and other abdominal lesions. Quantitative evaluation of CE-EUS images was an objective method of diagnosis using the time-intensity curve (TIC), but it was limited to the region of interest. Recently developed Inflow Time Mapping™ can be generated from stored clips and used to display the pattern of signal enhancement with time after injection, offering temporal difference of contrast agents and improved tumor characterization. On the other hand, three-dimensional CE-EUS images added new information to the literature, but lacked positional information. Three-dimensional CE-EUS with accurate positional information is awaited. To date, most reports have been related to pancreatic lesions or lymph nodes. Hemodynamic analysis might be of use for diseases in other organs: upper GI cancer diagnosis, submucosal tumors, and biliary disorders, and it might also provide functional information. Studies of CE-EUS in diseases in many other organs will increase in the near future.

  12. Contrast-Enhanced Ultrasonography in Crohn's Disease Diagnostics.

    Science.gov (United States)

    Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Liebert, Ariel; Kłopocka, Maria; Serafin, Zbigniew

    2015-06-01

    The chronic nature of Crohn's disease (CD) implicates necessity of multiple control assessments throughout patient's life. It is accepted that in patients with CD requiring disease monitoring, magnetic resonance enterography (MRE) and computed tomography enterography (CTE) are--apart from endoscopy--imaging studies of first choice. In practice, diagnostic imaging of patients with CD is troublesome, since MRE is an expensive and complicated study, and CTE exposes patients to high doses of ionizing radiation. Therefore, there is a need for new, both non-invasive and effective, methods of imaging in CD. Contrast-Enhanced Ultrasonography (CEUS) is a relatively new method using gas-filled microbubbles serving as contrast agent. It allows for detailed assessment of blood perfusion within intestine wall and peri-intestinal tissues, which enables detection and monitoring of inflammation and its qualitative assessment. The purpose of this paper is to describe CEUS examination technique and its clinical applications in patients with Crohn's disease.

  13. Diamox-enhanced brain SPECT in cerebrovascular diseases

    International Nuclear Information System (INIS)

    Choi, Yun Young

    2007-01-01

    Acute event in cerebrovascular disease is the second most common cause of death in Korea following cancer, and it can also cause serious neurologic deficits. Understanding of perfusion status is important for clinical applications in management of patients with cerebrovascular diseases, and then the attacks of ischemic neurologic symptoms and the risk of acute events can be reduced. Therefore, the normal vascular anatomy of brain, various clinical applications of acetazolamide-enhanced brain perfusion SPECT, including meaning and role of assessment of vascular reserve in carotid stenosis before procedure, in pediatric Moyamoya disease before and after operation, in prediction of development of hyperperfusion syndrome before procedure, and in prediction of vasospasm and of prognosis in subarachnoid hemorrhage were reviewed in this paper

  14. Enhanced tomato disease resistance primed by arbuscular mycorrhizal fungus.

    Science.gov (United States)

    Song, Yuanyuan; Chen, Dongmei; Lu, Kai; Sun, Zhongxiang; Zeng, Rensen

    2015-01-01

    Roots of most terrestrial plants form symbiotic associations (mycorrhiza) with soil- borne arbuscular mycorrhizal fungi (AMF). Many studies show that mycorrhizal colonization enhances plant resistance against pathogenic fungi. However, the mechanism of mycorrhiza-induced disease resistance remains equivocal. In this study, we found that mycorrhizal inoculation with AMF Funneliformis mosseae significantly alleviated tomato (Solanum lycopersicum Mill.) early blight disease caused by Alternaria solani Sorauer. AMF pre-inoculation led to significant increases in activities of β-1,3-glucanase, chitinase, phenylalanine ammonia-lyase (PAL) and lipoxygenase (LOX) in tomato leaves upon pathogen inoculation. Mycorrhizal inoculation alone did not influence the transcripts of most genes tested. However, pathogen attack on AMF-inoculated plants provoked strong defense responses of three genes encoding pathogenesis-related proteins, PR1, PR2, and PR3, as well as defense-related genes LOX, AOC, and PAL, in tomato leaves. The induction of defense responses in AMF pre-inoculated plants was much higher and more rapid than that in un-inoculated plants in present of pathogen infection. Three tomato genotypes: a Castlemart wild-type (WT) plant, a jasmonate (JA) biosynthesis mutant (spr2), and a prosystemin-overexpressing 35S::PS plant were used to examine the role of the JA signaling pathway in AMF-primed disease defense. Pathogen infection on mycorrhizal 35S::PS plants led to higher induction of defense-related genes and enzymes relative to WT plants. However, pathogen infection did not induce these genes and enzymes in mycorrhizal spr2 mutant plants. Bioassays showed that 35S::PS plants were more resistant and spr2 plants were more susceptible to early blight compared with WT plants. Our finding indicates that mycorrhizal colonization enhances tomato resistance to early blight by priming systemic defense response, and the JA signaling pathway is essential for mycorrhiza

  15. Environmental influences on antibody-enhanced dengue disease outcomes.

    Science.gov (United States)

    Diniz, Daniel Guerreiro; Fôro, César Augusto Raiol; Turiel, Maíra C Pereira; Sosthenes, Marcia C K; Demachki, Sâmia; Gomes, Giovanni Freitas; Rego, Carla M Damasceno; Magalhães, Marina Cutrim; Pinho, Brunno Gomes; Ramos, Juliana Pastana; Casseb, Samir M Moraes; Brito, Maysa de Vasconcelos; da Silva, Eliana Vieira Pinto; Nunes, Marcio Roberto Teixeira; Diniz, José Antonio Picanço; Cunningham, Colm; Perry, Victor Hugh; Vasconcelos, Pedro F Costa; Diniz, Cristovam W Picanço

    2012-12-01

    Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopathogenesis during heterologous dengue virus (DENV) infections, we hypothesised that an EE increases dengue severity. To compare single serotype (SS) and antibody-enhanced disease (AED) infections regimens, serial intraperitoneal were performed with DENV3 (genotype III) infected brain homogenate or anti-DENV2 hyperimmune serum followed 24 h later by DENV3 (genotype III) infected brain homogenate. Compared AED for which significant differences were detected between the EE and impoverished environmental (IE) groups (Kaplan-Meyer log-rank test, p = 0.0025), no significant differences were detected between the SS experimental groups (Kaplan-Meyer log-rank test, p = 0.089). Survival curves from EE and IE animals infected with the AED regimen were extended after corticoid injection and this effect was greater in the EE than in the IE group (Kaplan-Meyer log-rank test, p = 0.0162). Under the AED regimen the EE group showed more intense clinical signs than the IE group. Dyspnoea, tremor, hunched posture, ruffled fur, immobility, pre-terminal paralysis, shock and death were associated with dominant T-lymphocytic hyperplasia and presence of viral antigens in the liver and lungs. We propose that the increased expansion of these memory T-cells and serotype cross-reactive antibodies facilitates the infection of these cells by DENV and that these events correlate with disease severity in an EE.

  16. Enhancement and denoising of mammographic images for breast disease detection

    International Nuclear Information System (INIS)

    Yazdani, S.; Yusof, R.; Karimian, A.; Hematian, A.; Yousefi, M.

    2012-01-01

    In these two decades breast cancer is one of the leading cause of death among women. In breast cancer research, Mammographic Image is being assessed as a potential tool for detecting breast disease and investigating response to chemotherapy. In first stage of breast disease discovery, the density measurement of the breast in mammographic images provides very useful information. Because of the importance of the role of mammographic images the need for accurate and robust automated image enhancement techniques is becoming clear. Mammographic images have some disadvantages such as, the high dependence of contrast upon the way the image is acquired, weak distinction in splitting cyst from tumor, intensity non uniformity, the existence of noise, etc. These limitations make problem to detect the typical signs such as masses and microcalcifications. For this reason, denoising and enhancing the quality of mammographic images is very important. The method which is used in this paper is in spatial domain which its input includes high, intermediate and even very low contrast mammographic images based on specialist physician's view, while its output is processed images that show the input images with higher quality, more contrast and more details. In this research, 38 mammographic images have been used. The result of purposed method shows details of abnormal zones and the areas with defects so that specialist could explore these zones more accurately and it could be deemed as an index for cancer diagnosis. In this study, mammographic images are initially converted into digital images and then to increase spatial resolution power, their noise is reduced and consequently their contrast is improved. The results demonstrate effectiveness and efficiency of the proposed methods. (authors)

  17. Enhancing attention in neurodegenerative diseases: current therapies and future directions

    Directory of Open Access Journals (Sweden)

    Sharma Kanchan

    2016-01-01

    Full Text Available We all experience at least occasional lapses in attention but in some neurological conditions, loss of attention is pervasive and debilitating. Treating deficits in attention first requires an understanding of the neurobiology of attention, which we now understand to be a set of different cognitive processes. Cholinesterase inhibitors are already established as effective attentional enhancers used in the treatment of certain dementias. Other stimulant agents such as modafanil, amphetamine and methylphenidate have demonstrated limited success in healthy individuals where attention is already optimal and clinical trials in patients with neurological disease are sparse. Dietary and lifestyle changes are gaining increasing prominence, as are experimental treatments such as deep brain stimulation and transcranial magnetic stimulation. As the therapeutic arsenal widens, clinicians will be able to match specific treatments to selective deficits in attention, giving patients a tailored management plan. Here we review common diseases that impair attention and emphasise how an understanding of attentional processing within the brain might lead to improved therapeutic strategies.

  18. Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity.

    Science.gov (United States)

    De Franco, Antonio; Di Veronica, Alessandra; Armuzzi, Alessandro; Roberto, Italia; Marzo, Manuela; De Pascalis, Barbara; De Vitis, Italo; Papa, Alfredo; Bock, Enrico; Danza, Francesco M; Bonomo, Lorenzo; Guidi, Luisa

    2012-02-01

    To quantitatively assess microvascular activation in the thickened ileal walls of patients with Crohn disease (CD) by using contrast-enhanced ultrasonography (US) and evaluate its correlation with widely used indexes of CD activity. This prospective study was approved by the ethics committee, and written informed consent was obtained from all patients. The authors examined 54 consecutively enrolled patients (mean age, 35.29 years; age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the terminal ileum. Ileal wall segments thicker than 3 mm were examined with low-mechanical-index contrast-enhanced US and a second-generation US contrast agent. The authors analyzed software-plotted time-enhancement intensity curves to determine the maximum peak intensity (MPI) and wash-in slope coefficient (β) and evaluated their correlation with (a) the composite index of CD activity (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum. Statistical analysis was performed with the Mann-Whitney test, Spearman rank test, and receiver operating characteristic (ROC) analysis. MPI and β coefficients were significantly increased in the 36 patients with a CICDA indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES-CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed accurate identification (compared with CICDA) of active CD with an MPI threshold of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a β coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). Contrast-enhanced US of the ileal wall is a promising method for objective, reproducible assessment of disease activity in patients with ileal CD. © RSNA, 2011

  19. Mobile Health, a Key Factor Enhancing Disease Prevention Campaigns: Looking for Evidences in Kidney Disease Prevention

    Directory of Open Access Journals (Sweden)

    Nicole Roque Matias

    2017-01-01

    Full Text Available Background: Progressive chronic kidney disease (CKD failure and kidney diseases are increasing at an alarming rate all over the world. However, despite the remarkable advance in health technology, where it has become possible to successfully screen patients and predict kidney progression, a large portion of the world population is still unaware of their disease and risk exposure. Mobile Health (mHealth solutions associated with health campaigns and programs proved to be an effective mean to enhance awareness and behaviour change at individual and social level. Objective: The aim of this survey was to present the results of an environmental scan of what has been happening in the field of kidney disease prevention campaigns in recent years, with a focus on the use of mobile health as a tool to enhance the campaign's effects on targeting people and change their behaviour. Methodology: It was conducted a systematic and comprehensive review, combining experimental studies with theoretical perspectives, to look for evidence regarding the evaluation of kidney disease prevention campaigns. The databases consulted for the present survey were: MEDLINE, PubMed, Google Scholar, PsycINFO, SAGE Journals Online, and Web of Science among other sources, for an analysis period from January 2000 to June 2016. Results: Concerning the 14 analyzed examples with impact on kidney disease prevention campaign evaluation, two main campaigns were referred: The World Kidney Day (WKD campaign, and the Kidney Early Evaluation Program (KEEP. The indicators used in this analisys were in most cases comparable regarding the campaign messages, objectives and interventions tools, although em both cases the use of mHealth or other technologies is residually comparing to other diseases prevention campaigns or programs. Conclusions: This review pointed to the inexistence of behavioural change evidence as a target of the kidney disease prevention campaigns and their evaluation. General

  20. Adiponectin and adiponectin receptor 1 overexpression enhance inflammatory bowel disease.

    Science.gov (United States)

    Peng, Yu-Ju; Shen, Tang-Long; Chen, Yu-Shan; Mersmann, Harry John; Liu, Bing-Hsien; Ding, Shih-Torng

    2018-03-14

    Adiponectin (ADN) is an adipokine derived from adipocytes. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. We also treated a THP-1 macrophage and a HT-29 colon epithelial cell line with ADN recombinant protein to study the effects of ADN on inflammation. After inducing murine colitis, pAdipoR1 mice developed more severe symptoms than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells. Moreover, we also observed that the expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. Our study showed that ADN-AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and recruited neutrophils into the colonic tissue to increase inflammation.

  1. Medications Used for Cognitive Enhancement in Patients With Schizophrenia, Bipolar Disorder, Alzheimer’s Disease, and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Wen-Yu Hsu

    2018-04-01

    Full Text Available Background/aimsCognitive impairment, which frequently occurs in patients with schizophrenia, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease, has a significant impact on the daily lives of both patients and their family. Furthermore, since the medications used for cognitive enhancement have limited efficacy, the issue of cognitive enhancement still remains a clinically unsolved challenge.Sampling and methodsWe reviewed the clinical studies (published between 2007 and 2017 that focused on the efficacy of medications used for enhancing cognition in patients with schizophrenia, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease.ResultsAcetylcholinesterase inhibitors and memantine are the standard treatments for Alzheimer’s disease and Parkinson’s disease. Some studies have reported selective cognitive improvement in patients with schizophrenia following galantamine treatment. Newer antipsychotics, including paliperidone, lurasidone, aripiprazole, ziprasidone, and BL-1020, have also been reported to exert cognitive benefits in patients with schizophrenia. Dopaminergic medications were found to improve language function in patients with Parkinson’s disease. However, no beneficial effects on cognitive function were observed with dopamine agonists in patients with schizophrenia. The efficacies of nicotine and its receptor modulators in cognitive improvement remain controversial, with the majority of studies showing that varenicline significantly improved the cognitive function in schizophrenic patients. Several studies have reported that N-methyl-d-aspartate glutamate receptor (NMDAR enhancers improved the cognitive function in patients with chronic schizophrenia. NMDAR enhancers might also have cognitive benefits in patients with Alzheimer’s disease or Parkinson’s disease. Raloxifene, a selective estrogen receptor modulator, has also been demonstrated to have beneficial effects on attention, processing

  2. Microbial enrichment to enhance the disease suppressive activity of compost

    NARCIS (Netherlands)

    Postma, J.; Montenari, M.; Boogert, van den P.H.J.F.

    2003-01-01

    Compost amended soil has been found to be suppressive against plant diseases in various cropping systems. The level and reproducibility of disease suppressive properties of compost might be increased by the addition of antagonists. In the present study, the establishment and suppressive activity of

  3. Genetic enhancement of macroautophagy in vertebrate models of neurodegenerative diseases.

    Science.gov (United States)

    Ejlerskov, Patrick; Ashkenazi, Avraham; Rubinsztein, David C

    2018-04-03

    Most of the neurodegenerative diseases that afflict humans manifest with the intraneuronal accumulation of toxic proteins that are aggregate-prone. Extensive data in cell and neuronal models support the concept that such proteins, like mutant huntingtin or alpha-synuclein, are substrates for macroautophagy (hereafter autophagy). Furthermore, autophagy-inducing compounds lower the levels of such proteins and ameliorate their toxicity in diverse animal models of neurodegenerative diseases. However, most of these compounds also have autophagy-independent effects and it is important to understand if similar benefits are seen with genetic strategies that upregulate autophagy, as this strengthens the validity of this strategy in such diseases. Here we review studies in vertebrate models using genetic manipulations of core autophagy genes and describe how these improve pathology and neurodegeneration, supporting the validity of autophagy upregulation as a target for certain neurodegenerative diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qi Chen

    Full Text Available Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD, the focus is the amyloid beta peptide (Aß that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.

  5. Memory enhancing drugs and Alzheimer's disease: enhancing the self or preventing the loss of it?

    NARCIS (Netherlands)

    Dekkers, W.J.M.; Olde Rikkert, M.G.M.

    2007-01-01

    In this paper we analyse some ethical and philosophical questions related to the development of memory enhancing drugs (MEDs) and anti-dementia drugs. The world of memory enhancement is coloured by utopian thinking and by the desire for quicker, sharper, and more reliable memories. Dementia is

  6. Dynamic Contrast-Enhanced Magnetic Resonance Enterography and Dynamic Contrast-Enhanced Ultrasonography in Crohn's Disease

    DEFF Research Database (Denmark)

    Wilkens, Rune; Peters, David A; Nielsen, Agnete Hedemann

    2017-01-01

    Purpose e Cross-sectional imaging methods are important for objective evaluationof small intestinal inflammationinCrohn'sdisease(CD).The primary aim was to compare relative parameters of intestinal perfusion between contrast-enhanced ultrasonography (CEUS) and dynamic contrast-enhanced magnetic...

  7. Novel polymeric biochips for enhanced detection of infectious diseases

    CERN Document Server

    Hosseini, Samira

    2016-01-01

    This book focuses on the creation and development of polymeric platforms (different compositions) from a specific polymer system. This system can be used as an adaptive technique for producing sensitive analytical devices, or for simple integration into existing bioanalytical tools in order to enhance the detection signal.

  8. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

    NARCIS (Netherlands)

    van der Sanden, Sabine M. G.; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C.; Brooks, Paula; O'Donnell, Jason; Jones, Les P.; Brown, Cedric; Tompkins, S. Mark; Oberste, M. Steven; Karpilow, Jon; Tripp, Ralph A.

    2016-01-01

    Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced

  9. Efficacy of gadolinium enhanced MR imaging for the diagnosis of Legg-Calve-Perthes disease

    International Nuclear Information System (INIS)

    Kim, Jee Eun; Kim, Hyung Sik; Kim, Ji Hye

    2008-01-01

    The purpose of this study was to evaluate the efficacy of gadolinium enhanced MR imaging for making the diagnosis of Legg-Calve-Perthes (LCP) disease. We studied the gadolinium enhanced MR images of 14 hips in 12 children who had the diagnosis of LCP disease. We retrospectively analyzed the extent of necrosis, the epiphyseal revascularization pathways and the metaphyseal changes. The absence of enhancement on gadolinium enhanced MRI was noted in all cases of LCP disease. Diffuse absence of enhancement was observed in 9 femoral epiphyses. Two of them showed normal bone marrow signal intensity on the T1 and T1-weighted images. Focal absence of enhancement was observed in 5 femoral epiphyses. Enhanced MRI showed better epiphyseal revascularization in the lateral column (five cases), in the lateral and medial columns (four cases) and in the transphyseal pathway (three cases). Metaphyseal change was observed in two cases. Gadolinium enhanced MRI allows detection of LCP disease and an accurate analysis of the different revascularization patterns, and this helpful for predicting the prognosis

  10. Enhancement on infectious diseases nursing plan information system.

    Science.gov (United States)

    Yeh, Mei-Lin; Hao, Te-Hui; Hsu, Chien-Yeh

    2009-01-01

    Based on researches, the most time-consuming nursing activities, in teaching hospital, are: room patrols, the blood pressure survey, the body temperature pulse breath survey, the nursing record maintenance. The nursing record is one way to communicate data. It can allow the medical service team to understand what measures the nursing staff once did for sickness, as well as responses from sickness. Nevertheless, it is the key component to utilize the record with a clinical nursing plan, so as to provide a proficient health management. Since the maintenance of nursing plan is costly and time-consuming, therefore, it is essential to establish the nursing plan information system, which can effectively promote the nursing quality. This research main body comes from one infectious disease division nursing plan information system, which was developed in 1992, and its data base covers entire courtyard compatibility and various faculties characteristic nursing plan. The nursing staff often complained that this system is not user-friendly, its contents are not comprehensive, and sometimes it does not let staff choose the right diagnosis. Therefore this research is based on history analysis and the questionnaire survey procedure first, the infectious disease nursing plan use number of times, the frequency and the project content, then by the literature scientific theory and result of the improvement group discussion together. The original 38 infectious disease division nursing plan will be expanded to 45 nursing plans. Moreover, the common 38 infectious disease code (ICD-9), and its corresponding diagnosis items, shall automatically appear in the disease diagnose code field, so it would be better off for the nursing staff to set up the nursing plan efficiently. Infectious disease division nursing plan information system utilization ratio is promoted 9.6-folds, according to research outcome. Each task consumes 3.68 minutes beforehand-including computer program operation, the

  11. Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease

    NARCIS (Netherlands)

    Ziech, M. L. W.; Lavini, C.; Caan, M. W. A.; Nio, C. Y.; Stokkers, P. C. F.; Bipat, S.; Ponsioen, C. Y.; Nederveen, A. J.; Stoker, J.

    2012-01-01

    Objectives: To prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. Methods: Patients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of

  12. Quantitative analysis of contrast-enhanced ultrasonography of the bowel wall can predict disease activity in inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Romanini, Laura, E-mail: laura.romanini@libero.it [Department of Radiology, Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia (Italy); Passamonti, Matteo, E-mail: matteopassamonti@gmail.com [Department of Radiology-AO Provincia di Lodi, Via Fissiraga, 15, 26900 Lodi (Italy); Navarria, Mario, E-mail: navarria.mario@tiscali.it [Department of Radiology-ASL Vallecamonica-Sebino, Via Manzoni 142, 25040 Esine, BS (Italy); Lanzarotto, Francesco, E-mail: francesco.lanzarotto@spedalicivili.brescia.it [Department of Gastroenterology, Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia (Italy); Villanacci, Vincenzo, E-mail: villanac@alice.it [Department of Pathology, Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia (Italy); Grazioli, Luigi, E-mail: radiologia1@spedalicivili.brescia.it [Department of Radiology, Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia (Italy); Calliada, Fabrizio, E-mail: fabrizio.calliada@gmail.com [Department of Radiology, University of Pavia, Viale Camillo Golgi 19, 27100 Pavia (Italy); Maroldi, Roberto, E-mail: rmaroldi@gmail.com [Department of Radiology, University of Brescia, P.le Spedali Civili, 1, 25123 Brescia (Italy)

    2014-08-15

    Purpose: To evaluate the accuracy of quantitative analysis of bowel wall enhancement in inflammatory bowel disease (IBD) with contrast enhanced ultrasound (CEUS) by comparing the results with vascular density in a biopsy sample from the same area of the intestinal tract, and to determine the usefulness of this analysis for the prediction of disease activity. Materials and methods: This prospective study was approved by our institute's ethics committee and all patients gave written informed consent. We enrolled 33 consecutive adult patients undergoing colonoscopy and biopsy for IBD. All patients underwent CEUS and the results were quantitatively analyzed. Vessel count per high-power field on biopsy specimens was compared with colonoscopy, baseline ultrasonography, and CEUS findings, and with analysis of peak intensity, time to peak, regional blood volume, mean transit time, and regional blood flow. Results in patients with high and low vascular density were compared using Fisher's test, t-test, Pearson's correlation test, and receiver operating characteristic curve (ROC) analysis. Cutoff values were determined using ROC analysis, and sensitivity and specificity were calculated. Results: High vascular density (>265 vessels per field) on histological examination was significantly correlated with active disease on colonoscopy, baseline ultrasonography, and CEUS (p < .0001). Quantitative analysis showed a higher enhancement peak, a shorter time to peak enhancement, a higher regional blood flow and regional blood volume in patients with high vascular density than in those with low vascular density. Cutoff values to distinguish between active and inactive disease were identified for peak enhancement (>40.5%), and regional blood flow (>54.8 ml/min). Conclusion: Quantitative analysis of CEUS data correlates with disease activity as determined by vascular density. Quantitative parameters of CEUS can be used to predict active disease with high sensitivity and

  13. Quantitative analysis of contrast-enhanced ultrasonography of the bowel wall can predict disease activity in inflammatory bowel disease

    International Nuclear Information System (INIS)

    Romanini, Laura; Passamonti, Matteo; Navarria, Mario; Lanzarotto, Francesco; Villanacci, Vincenzo; Grazioli, Luigi; Calliada, Fabrizio; Maroldi, Roberto

    2014-01-01

    Purpose: To evaluate the accuracy of quantitative analysis of bowel wall enhancement in inflammatory bowel disease (IBD) with contrast enhanced ultrasound (CEUS) by comparing the results with vascular density in a biopsy sample from the same area of the intestinal tract, and to determine the usefulness of this analysis for the prediction of disease activity. Materials and methods: This prospective study was approved by our institute's ethics committee and all patients gave written informed consent. We enrolled 33 consecutive adult patients undergoing colonoscopy and biopsy for IBD. All patients underwent CEUS and the results were quantitatively analyzed. Vessel count per high-power field on biopsy specimens was compared with colonoscopy, baseline ultrasonography, and CEUS findings, and with analysis of peak intensity, time to peak, regional blood volume, mean transit time, and regional blood flow. Results in patients with high and low vascular density were compared using Fisher's test, t-test, Pearson's correlation test, and receiver operating characteristic curve (ROC) analysis. Cutoff values were determined using ROC analysis, and sensitivity and specificity were calculated. Results: High vascular density (>265 vessels per field) on histological examination was significantly correlated with active disease on colonoscopy, baseline ultrasonography, and CEUS (p < .0001). Quantitative analysis showed a higher enhancement peak, a shorter time to peak enhancement, a higher regional blood flow and regional blood volume in patients with high vascular density than in those with low vascular density. Cutoff values to distinguish between active and inactive disease were identified for peak enhancement (>40.5%), and regional blood flow (>54.8 ml/min). Conclusion: Quantitative analysis of CEUS data correlates with disease activity as determined by vascular density. Quantitative parameters of CEUS can be used to predict active disease with high sensitivity and

  14. Activity enhances dopaminergic long-duration response in Parkinson disease

    Science.gov (United States)

    Auinger, Peggy; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Marek, Kenneth; Seibyl, John; Lang, Anthony; Olanow, C. Warren; Tanner, Caroline; Schifitto, Giovanni; Zhao, Hongwei; Reyes, Lydia; Shinaman, Aileen; Comella, Cynthia L.; Goetz, Christopher; Blasucci, Lucia M.; Samanta, Johan; Stacy, Mark; Williamson, Kelli; Harrigan, Mary; Greene, Paul; Ford, Blair; Moskowitz, Carol; Truong, Daniel D.; Pathak, Mayank; Jankovic, Joseph; Ondo, William; Atassi, Farah; Hunter, Christine; Jacques, Carol; Friedman, Joseph H.; Lannon, Margaret; Russell, David S.; Jennings, Danna; Fussell, Barbara; Standaert, David; Schwarzschild, Michael A.; Growdon, John H.; Tennis, Marsha; Gauthier, Serge; Panisset, Michel; Hall, Jean; Gancher, Stephen; Hammerstad, John P.; Stone, Claudia; Alexander-Brown, Barbara; Factor, Stewart A.; Molho, Eric; Brown, Diane; Evans, Sharon; Clark, Jeffrey; Manyam, Bala; Simpson, Patricia; Wulbrecht, Brian; Whetteckey, Jacqueline; Martin, Wayne; Roberts, Ted; King, Pamela; Hauser, Robert; Zesiewicz, Theresa; Gauger, Lisa; Trugman, Joel; Wooten, G. Frederick; Rost-Ruffner, Elke; Perlmutter, Joel; Racette, Brad A.; Suchowersky, Oksana; Ranawaya, Ranjit; Wood, Susan; Pantella, Carol; Kurlan, Roger; Richard, Irene; Pearson, Nancy; Caviness, John N.; Adler, Charles; Lind, Marlene; Simuni, Tanya; Siderowf, Andrew; Colcher, Amy; Lloyd, Mary; Weiner, William; Shulman, Lisa; Koller, William; Lyons, Kelly; Feldman, Robert G.; Saint-Hilaire, Marie H.; Ellias, Samuel; Thomas, Cathi-Ann; Juncos, Jorge; Watts, Ray; Partlow, Anna; Tetrud, James; Togasaki, Daniel M.; Stewart, Tracy; Mark, Margery H.; Sage, Jacob I.; Caputo, Debbie; Gould, Harry; Rao, Jayaraman; McKendrick, Ann; Brin, Mitchell; Danisi, Fabio; Benabou, Reina; Hubble, Jean; Paulson, George W.; Reider, Carson; Birnbaum, Alex; Miyasaki, Janis; Johnston, Lisa; So, Julie; Pahwa, Rajesh; Dubinsky, Richard M.; Wszolek, Zbigniew; Uitti, Ryan; Turk, Margaret; Tuite, Paul; Rottenberg, David; Hansen, Joy; Ramos, Serrano; Waters, Cheryl; Lew, Mark; Welsh, Mickie; Kawai, Connie; O'Brien, Christopher; Kumar, Rajeev; Seeberger, Lauren; Judd, Deborah; Barclay, C. Lynn; Grimes, David A.; Sutherland, Laura; Dawson, Ted; Reich, Stephen; Dunlop, Rebecca; Albin, Roger; Frey, Kirk; Wernette, Kristine; Mendis, Tilak

    2012-01-01

    Objective: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. Methods: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks. Results: The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands. Conclusions: Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during “off” medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects. PMID:22459675

  15. Brassinosteroid enhances resistance to fusarium diseases of barley.

    Science.gov (United States)

    Ali, Shahin S; Kumar, G B Sunil; Khan, Mojibur; Doohan, Fiona M

    2013-12-01

    Fusarium pathogens are among the most damaging pathogens of cereals. These pathogens have the ability to attack the roots, seedlings, and flowering heads of barley and wheat plants with disease, resulting in yield loss and head blight disease and also resulting in the contamination of grain with mycotoxins harmful to human and animal health. There is increasing evidence that brassinosteroid (BR) hormones play an important role in plant defense against both biotic and abiotic stress agents and this study set out to determine if and how BR might affect Fusarium diseases of barley. Application of the epibrassinolide (epiBL) to heads of 'Lux' barley reduced the severity of Fusarium head blight (FHB) caused by Fusarium culmorum by 86% and reduced the FHB-associated loss in grain weight by 33%. Growth of plants in soil amended with epiBL resulted in a 28 and 35% reduction in Fusarium seedling blight (FSB) symptoms on the Lux and 'Akashinriki' barley, respectively. Microarray analysis was used to determine whether growth in epiBL-amended soil changed the transcriptional profile in stem base tissue during the early stages of FSB development. At 24 and 48 h post F. culmorum inoculation, there were 146 epiBL-responsive transcripts, the majority being from the 48-h time point (n = 118). Real-time reverse-transcription polymerase chain reaction analysis validated the results for eight transcripts, including five defense genes. The results of gene expression studies show that chromatin remodeling, hormonal signaling, photosynthesis, and pathogenesis-related genes are activated in plants as a result of growth in epiBL.

  16. Feeder density enhances house finch disease transmission in experimental epidemics.

    Science.gov (United States)

    Moyers, Sahnzi C; Adelman, James S; Farine, Damien R; Thomason, Courtney A; Hawley, Dana M

    2018-05-05

    Anthropogenic food provisioning of wildlife can alter the frequency of contacts among hosts and between hosts and environmental sources of pathogens. Despite the popularity of garden bird feeding, few studies have addressed how feeders influence host contact rates and disease dynamics. We experimentally manipulated feeder density in replicate aviaries containing captive, pathogen-naive, groups of house finches ( Haemorhous mexicanus ) and continuously tracked behaviours at feeders using radio-frequency identification devices. We then inoculated one bird per group with Mycoplasma gallisepticum (Mg), a common bacterial pathogen for which feeders are fomites of transmission, and assessed effects of feeder density on house finch behaviour and pathogen transmission. We found that pathogen transmission was significantly higher in groups with the highest density of bird feeders, despite a significantly lower rate of intraspecific aggressive interactions relative to the low feeder density groups. Conversely, among naive group members that never showed signs of disease, we saw significantly higher concentrations of Mg-specific antibodies in low feeder density groups, suggesting that birds in low feeder density treatments had exposure to subclinical doses of Mg. We discuss ways in which the density of garden bird feeders could play an important role in mediating the intensity of Mg epidemics.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'. © 2018 The Author(s).

  17. Sequential gadolinium-DTPA enhanced MRI studies in neuro-Behcet's disease

    International Nuclear Information System (INIS)

    Kazui, S.; Naritomi, H.; Ogawa, M.; Sawada, T.; Imakita, S.; Yamada, N.

    1991-01-01

    Sequential gadolinium-DTPA (Gd-DTPA) enhanced MR images were obtained before and after steroid therapy in a case of neuro-Behcet's disease. Multiple scattered lesions, which could not be detected on pre- and post-contrast CT, were demonstrated mainly in the white matter of the pons and/or the cerebrum with both T1- and T2-weighted images. Some of these lesions, however, were not enhanced at all by infusion of Gd-DTPA. The Gd-DTPA infusion study demonstrated marked enhancement in the white matter of the pons and cerebrum. Some lesions not seen with T2-weighted images were also strongly enhanced by Gd-DTPA infusion at the acute stage. After steroid therapy, the symptoms and abnormal laboratory findings were resolved. The pontine and cerebral lesions on plain MR images remained unchanged even after resolution of the symptoms, suggesting that they were inactive old foci. On the other hand, the lesions detected in the enhancement study before steroid therapy disappeared with the repeat Gd-DTPA enhanced MR images which were performed after resolution of the symptoms. Some active inflammatory lesions in neuro-Behcet's disease may be demonstrated only on Gd-DTPA enhanced MR images. Gd-DTPA enhanced MR imaging appears to be potentially useful for detecting active inflammatory lesions in neuro-Behcet's disease and for evaluating the efficacy of treatment. (orig.)

  18. Music as a memory enhancer in patients with Alzheimer's disease.

    Science.gov (United States)

    Simmons-Stern, Nicholas R; Budson, Andrew E; Ally, Brandon A

    2010-08-01

    Musical mnemonics have a long and diverse history of popular use. In addition, music processing in general is often considered spared by the neurodegenerative effects of Alzheimer's disease (AD). Research examining these two phenomena is limited, and no work to our knowledge has explored the effectiveness of musical mnemonics in AD. The present study sought to investigate the effect of music at encoding on the subsequent recognition of associated verbal information. Lyrics of unfamiliar children's songs were presented bimodally at encoding, and visual stimuli were accompanied by either a sung or a spoken recording. Patients with AD demonstrated better recognition accuracy for the sung lyrics than the spoken lyrics, while healthy older adults showed no significant difference between the two conditions. We propose two possible explanations for these findings: first, that the brain areas subserving music processing may be preferentially spared by AD, allowing a more holistic encoding that facilitates recognition, and second, that music heightens arousal in patients with AD, allowing better attention and improved memory. Published by Elsevier Ltd.

  19. Enhanced Feedback-Related Negativity in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Shuhei Yamaguchi

    2017-04-01

    Full Text Available Alzheimer’s disease (AD, the most common cause of dementia in the elderly, results in the impairment of executive function, including that of performance monitoring. Feedback-related negativity (FRN is an electrophysiological measure reflecting the activity of this monitoring system via feedback signals, and is generated from the anterior cingulate cortex. However, there have been no reports on FRN in AD. Based on prior aging studies, we hypothesized that FRN would decrease in AD patients. To assess this, FRN was measured in healthy individuals and those with AD during a simple gambling task involving positive and negative feedback stimuli. Contrary to our hypothesis, FRN amplitude increased in AD patients, compared with the healthy elderly. We speculate that this may reflect the existence of a compensatory mechanism against the decline in executive function. Also, there was a significant association between FRN amplitude and depression scores in AD, and the FRN amplitude tended to increase insomuch as the Self-rating Depression Scale (SDS was higher. This result suggests the existence of a negative bias in the affective state in AD. Thus, the impaired functioning monitoring system in AD is a more complex phenomenon than we thought.

  20. Music enhances verbal episodic memory in Alzheimer's disease.

    Science.gov (United States)

    Palisson, Juliette; Roussel-Baclet, Caroline; Maillet, Didier; Belin, Catherine; Ankri, Joël; Narme, Pauline

    2015-01-01

    Although previous studies suggest that music may facilitate verbal learning in a healthy population, such a mnemonic effect has seldom been investigated in Alzheimer's disease (AD). Moreover, memorization of texts was generally compared when either sung or spoken. In the present study, it was examined whether the benefit observed on verbal learning was specific to music or whether an associative context binding items together led to similar benefits, regardless of the nature of the association. Twelve patients with mild AD and 15 healthy controls learned texts presented with either a musical (sung) or a nonmusical association (spoken associated to a silent movie sequence) or without association (spoken alone). Immediate and delayed (after a 5-min delay) recall was measured. Main results showed that (a) sung texts were better remembered than spoken texts, both immediately and after a retention delay, for both groups; (b) the musical benefit was robust, being observed in most AD patients; (c) the nonmusical association may also facilitate verbal learning but to a lesser extent. A musical association during the encoding stage facilitates learning and retention in AD. Furthermore, this advantage seemed quite specific to music. The results are discussed with respect to the clinical applications in AD; theoretical implications are highlighted to explain the power of music as a mnemonic technique.

  1. Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease.

    Science.gov (United States)

    Borchert, Robin J; Rittman, Timothy; Passamonti, Luca; Ye, Zheng; Sami, Saber; Jones, Simon P; Nombela, Cristina; Vázquez Rodríguez, Patricia; Vatansever, Deniz; Rae, Charlotte L; Hughes, Laura E; Robbins, Trevor W; Rowe, James B

    2016-07-01

    Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.

  2. Chronological evaluation of liver enhancement in patients with chronic liver disease at Gd-EOB-DTPA-enhanced 3-T MR imaging. Does liver function correlate with enhancement?

    International Nuclear Information System (INIS)

    Nakamura, Shinichi; Utsunomiya, Daisuke; Namimoto, Tomohiro; Yamashita, Yasuyuki; Awai, Kazuo; Nakaura, Takeshi; Morita, Kosuke

    2012-01-01

    The purpose of this study was to investigate the chronological relationship between scan delay and liver enhancement for the hepatobiliary phase on Gd-EOB-DTPA-enhanced MRI and evaluate the effects of liver function on liver enhancement. Hepatobiliary-phase images were retrospectively evaluated in 125 patients with chronic liver disease. Hepatobiliary phase images were obtained at 5, 10, 15, and 20 min after injection. We calculated relative liver enhancement (RLE) at t min after injection by dividing the signal intensity (SI) of the liver at t min by precontrast SI. We compared RLE values at 5, 10, 15, and 20 min and evaluated the detectability of focal hepatic lesions. We analyzed the effect of liver function on RLE with the generalized linear model. There was not significant difference in RLE and lesion detectability at 15 and 20 min. RLE in the Child-Pugh C group was significantly lower than in the Child-Pugh A and B groups. The serum albumin level and prothrombin time were significantly correlated with the liver enhancement. A delay time of 15 min for the hepatobiliary phase was thought to be adequate in patients with mild liver dysfunction. The serum albumin level and prothrombin time would be predictive of liver enhancement in the hepatobiliary phase. (author)

  3. Contrast-enhanced ultrasonography for the determination of Crohn’s disease activity – preliminary experience

    Science.gov (United States)

    Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Kłopocka, Maria; Liebert, Ariel; Lemanowicz, Adam; Serafin, Zbigniew

    2014-01-01

    Summary Background Contrast-enhanced ultrasound (CEUS) is a recent non-invasive modality, which may partially replace currently used techniques (endoscopy, CT enterography and MR enterography) in the diagnostics and assessment of Crohn’s disease (CD). The aim of the study was to analyze early experience in the use of CEUS for the measurement of activity and staging of CD. Material/Methods Eleven patients previously diagnosed with CD were included in the study. They underwent contrast-enhanced ultrasonography (SonoVue, Bracco), low-dose CT enterography (LDCTE), assessment of laboratory markers of inflammation and clinical CD activity index (CDAI). Contrast enhancement was evaluated using a semi-quantitative method and a quantitative method that included measurement of peak enhancement (PE), enhancement curve rise time (RT) and wash-in-rate (WiR). Results Ileal wall thickening was observed in all patients. Semi-quantitative method was used to observe CD activity in CEUS in 10 cases that perfectly matched LDCTE findings. There was a moderate positive correlation between PE and CDAI (r=0.65, p<0.001). There was no significant relationship between perfusion parameters and laboratory markers of inflammation. Conclusions CEUS is a promising modality for non-invasive assessment of pathologic ileal vascularization in the course of Crohn’s disease. Intensity of enhancement in CEUS reflects activity of the disease detected in LDCTE and correlates with CDAI. PMID:24723988

  4. Contrast-enhanced ultrasonography for the determination of Crohn's disease activity - preliminary experience.

    Science.gov (United States)

    Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Kłopocka, Maria; Liebert, Ariel; Lemanowicz, Adam; Serafin, Zbigniew

    2014-01-01

    Contrast-enhanced ultrasound (CEUS) is a recent non-invasive modality, which may partially replace currently used techniques (endoscopy, CT enterography and MR enterography) in the diagnostics and assessment of Crohn's disease (CD). The aim of the study was to analyze early experience in the use of CEUS for the measurement of activity and staging of CD. Eleven patients previously diagnosed with CD were included in the study. They underwent contrast-enhanced ultrasonography (SonoVue, Bracco), low-dose CT enterography (LDCTE), assessment of laboratory markers of inflammation and clinical CD activity index (CDAI). Contrast enhancement was evaluated using a semi-quantitative method and a quantitative method that included measurement of peak enhancement (PE), enhancement curve rise time (RT) and wash-in-rate (WiR). Ileal wall thickening was observed in all patients. Semi-quantitative method was used to observe CD activity in CEUS in 10 cases that perfectly matched LDCTE findings. There was a moderate positive correlation between PE and CDAI (r=0.65, p<0.001). There was no significant relationship between perfusion parameters and laboratory markers of inflammation. CEUS is a promising modality for non-invasive assessment of pathologic ileal vascularization in the course of Crohn's disease. Intensity of enhancement in CEUS reflects activity of the disease detected in LDCTE and correlates with CDAI.

  5. Contrast-enhanced ultrasonography for the determination of Crohn’s disease activity – preliminary experience

    International Nuclear Information System (INIS)

    Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Kłopocka, Maria; Liebert, Ariel; Lemanowicz, Adam; Serafin, Zbigniew

    2014-01-01

    Contrast-enhanced ultrasound (CEUS) is a recent non-invasive modality, which may partially replace currently used techniques (endoscopy, CT enterography and MR enterography) in the diagnostics and assessment of Crohn’s disease (CD). The aim of the study was to analyze early experience in the use of CEUS for the measurement of activity and staging of CD. Eleven patients previously diagnosed with CD were included in the study. They underwent contrast-enhanced ultrasonography (SonoVue, Bracco), low-dose CT enterography (LDCTE), assessment of laboratory markers of inflammation and clinical CD activity index (CDAI). Contrast enhancement was evaluated using a semi-quantitative method and a quantitative method that included measurement of peak enhancement (PE), enhancement curve rise time (RT) and wash-in-rate (WiR). Ileal wall thickening was observed in all patients. Semi-quantitative method was used to observe CD activity in CEUS in 10 cases that perfectly matched LDCTE findings. There was a moderate positive correlation between PE and CDAI (r=0.65, p<0.001). There was no significant relationship between perfusion parameters and laboratory markers of inflammation. CEUS is a promising modality for non-invasive assessment of pathologic ileal vascularization in the course of Crohn’s disease. Intensity of enhancement in CEUS reflects activity of the disease detected in LDCTE and correlates with CDAI

  6. Gadolinium-enhanced MRI in central nervous system Behcet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Erdem, E. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France)); Carlier, R. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France)); Idir, A.B.C. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France)); Masnou, P.O. (Dept. of Neurology, Hopital de Bicetre, Paris-Sud Univ. (France)); Moulonguet, A. (Dept. of Neurology, Hopital de Bicetre, Paris-Sud Univ. (France)); Adams, D. (Dept. of Neurology, Hopital de Bicetre, Paris-Sud Univ. (France)); Doyon, D. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France))

    1993-02-01

    Two cases of central nervous system Behcet's disease, studied by gadolinium-enhanced MRI, are presented. In one patient, whose clinical picture was dominated by a brain stem syndrome, the gadolinium enhancement resolved with clinical improvement, although the hyperintense areas in the mesencephalon on T2-weighted images persisted. In the second, who had a pseudobulbar palsy and a mild right hemiparesis, there were many abnormal areas, but an enhancing focus in the posterior limb of the left internal capsule was probably the lesion responsible for the hemiparesis. (orig.)

  7. Neurosarcoidosis--demonstration of meningeal disease by gadolinium enhanced magnetic resonance imaging.

    Science.gov (United States)

    Khaw, K T; Manji, H; Britton, J; Schon, F

    1991-01-01

    Arriving at a firm diagnosis of neurosarcoidosis continues to pose serious problems, particularly when evidence of granulomatous disease outside the nervous system is lacking. The commonest mode of presentation of neurosarcoidosis is with cranial nerve palsies. Two cases of presumed neurosarcoidosis with cranial nerve palsies showed clear evidence of focal meningeal disease on gadolinium-DTPA enhanced MRI brain scans. Although not specific for sarcoidosis, this technique may be very useful in aiding the diagnosis in suspected cases. Images PMID:1880510

  8. Accuracy of nursing diagnosis "readiness for enhanced hope" in patients with chronic kidney disease.

    Science.gov (United States)

    Silva, Renan Alves; Melo, Geórgia Alcântara Alencar; Caetano, Joselany Áfio; Lopes, Marcos Venícios Oliveira; Butcher, Howard Karl; Silva, Viviane Martins da

    2017-07-06

    To analyse the accuracy of the nursing diagnosis readiness for enhanced hope in patients with chronic kidney disease. This is a cross-sectional study with 62 patients in the haemodialysis clinic conducted from August to November 2015. The Hearth Hope Scale was used to create definitions of the defining characteristics of the North American Nursing Diagnosis Association International. We analysed the measures of sensitivity, specificity, predictive value, likelihood ratio, and odds ratio of the defining characteristics of the diagnosis. Of the characteristics, 82.22% presented the diagnosis. The defining characteristics "Expresses the desire to enhance congruency of expectations with desires" and "Expresses the desire to enhance problem solving to meet goals" increased the chance of having the diagnosis by eleven and five, respectively. The characteristics, "Expresses desire to enhance congruency of expectations with desires" and "Expresses desire to enhance problem solving to meet goals" had good accuracy measures.

  9. Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease

    International Nuclear Information System (INIS)

    Ziech, M.L.W.; Lavini, C.; Caan, M.W.A.; Nio, C.Y.; Stokkers, P.C.F.; Bipat, S.; Ponsioen, C.Y.; Nederveen, A.J.; Stoker, J.

    2012-01-01

    Objectives: To prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. Methods: Patients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of gadobutrol, single shot fast spin echo sequence and 3D T1-weighted spoiled gradient echo sequence, a dynamic coronal 3D T1-weighted fast spoiled gradient were performed before and after gadobutrol. Maximum enhancement (ME) and initial slope of increase (ISI) were calculated for four colon segments (ascending colon + coecum, transverse colon, descending colon + sigmoid, rectum) and (neo)terminal ileum. C-reactive protein (CRP), Crohn's disease activity index (CDAI), per patient and per segment Crohn's disease endoscopic index of severity (CDEIS) and disease duration were determined. Mean values of the (DCE-)MRI parameters in each segment from each patient were compared between four disease activity groups (normal mucosa, non-ulcerative lesions, mild ulcerative and severe ulcerative disease) with Mann–Whitney test with Bonferroni adjustment. Spearman correlation coefficients were calculated for continuous variables. Results: Thirty-three patients were included (mean age 37 years; 23 females, median CDEIS 4.4). ME and ISI correlated weakly with segmental CDEIS (r = 0.485 and r = 0.206) and ME per patient correlated moderately with CDEIS (r = 0.551). ME was significantly higher in segments with mild (0.378) or severe (0.388) ulcerative disease compared to normal mucosa (0.304) (p < 0.001). No ulcerations were identified at conventional sequences. ME correlated with disease duration in diseased segments (r = 0.492), not with CDAI and CRP. Conclusions: DCE-MRI can be used as a method for detecting Crohn's disease ulcerative lesions.

  10. Dynamic contrast-enhanced MRI in patients with luminal Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Ziech, M.L.W., E-mail: m.l.ziech@amc.uva.nl [Academic Medical Center, Department of Radiology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Lavini, C., E-mail: c.lavini@amc.uva.nl [Academic Medical Center, Department of Radiology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Caan, M.W.A., E-mail: m.w.a.caan@amc.uva.nl [Academic Medical Center, Department of Radiology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Nio, C.Y., E-mail: C.Y.Nio@amc.uva.nl [Academic Medical Center, Department of Radiology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Stokkers, P.C.F., E-mail: p.stokkers@slaz.nl [Academic Medical Center, Department of Gastroenterology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Sint Lucas Andreas Ziekenhuis, Department of Gastroenterology, Jan Tooropstraat 164, 1061 AE, Amsterdam (Netherlands); Bipat, S., E-mail: S.Bipat@amc.uva.nl [Academic Medical Center, Department of Radiology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Ponsioen, C.Y., E-mail: c.y.ponsioen@amc.uva.nl [Academic Medical Center, Department of Gastroenterology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Nederveen, A.J., E-mail: a.j.nederveen@amc.uva.nl [Academic Medical Center, Department of Radiology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands); Stoker, J., E-mail: j.stoker@amc.uva.nl [Academic Medical Center, Department of Radiology, Meibergdreef 9, 1105 AZ, Amsterdam (Netherlands)

    2012-11-15

    Objectives: To prospectively assess dynamic contrast-enhanced (DCE-)MRI as compared to conventional sequences in patients with luminal Crohn's disease. Methods: Patients with Crohn's disease undergoing MRI and ileocolonoscopy within 1 month had DCE-MRI (3T) during intravenous contrast injection of gadobutrol, single shot fast spin echo sequence and 3D T1-weighted spoiled gradient echo sequence, a dynamic coronal 3D T1-weighted fast spoiled gradient were performed before and after gadobutrol. Maximum enhancement (ME) and initial slope of increase (ISI) were calculated for four colon segments (ascending colon + coecum, transverse colon, descending colon + sigmoid, rectum) and (neo)terminal ileum. C-reactive protein (CRP), Crohn's disease activity index (CDAI), per patient and per segment Crohn's disease endoscopic index of severity (CDEIS) and disease duration were determined. Mean values of the (DCE-)MRI parameters in each segment from each patient were compared between four disease activity groups (normal mucosa, non-ulcerative lesions, mild ulcerative and severe ulcerative disease) with Mann-Whitney test with Bonferroni adjustment. Spearman correlation coefficients were calculated for continuous variables. Results: Thirty-three patients were included (mean age 37 years; 23 females, median CDEIS 4.4). ME and ISI correlated weakly with segmental CDEIS (r = 0.485 and r = 0.206) and ME per patient correlated moderately with CDEIS (r = 0.551). ME was significantly higher in segments with mild (0.378) or severe (0.388) ulcerative disease compared to normal mucosa (0.304) (p < 0.001). No ulcerations were identified at conventional sequences. ME correlated with disease duration in diseased segments (r = 0.492), not with CDAI and CRP. Conclusions: DCE-MRI can be used as a method for detecting Crohn's disease ulcerative lesions.

  11. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    International Nuclear Information System (INIS)

    Ayyala, Rama S.; Teot, Lisa A.; Perez Rossello, Jeanette M.

    2017-01-01

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  12. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

    2017-04-15

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  13. Addison's disease due to adrenal tuberculosis: Contrast-enhanced CT features and clinical duration correlation

    International Nuclear Information System (INIS)

    Guo Yingkun; Yang Zhigang; Li Yuan; Ma Ensen; Deng Yuping; Min Pengqiu; Yin Longlin; Hu Jian; Zhang Xiaochun; Chen Tianwu

    2007-01-01

    Purpose: To describe CT morphology of untreated adrenal tuberculosis during the different stages of the natural history of the disease and to evaluate the diagnostic implications of CT features. Materials and methods: We retrospectively evaluated CT features in 42 patients with documented adrenal tuberculosis for the location, size, morphology, and enhancement patterns shown on CT images. The clinical duration were correlated with the CT features. Results: Of the 42 patients with untreated adrenal tuberculosis, bilaterally enlarged adrenal glands were revealed in 38 cases (91%), unilaterally enlarged in 3 cases (7%), and normal size in 1 case (2%). Of the 41 cases (98%) with enlargement, mass-like enlargement was seen in 20 cases (49%) and enlargement with preserved contours in 21 cases (51%). Peripheral rim enhancement presented in 22 cases (52%) on contrast-enhanced CT. Non-enhanced CT scan revealed calcification in 21 cases (50%). As the duration of Addison's disease increased, the presence of calcification and contour preservation increased concomitantly (p < 0.001), whereas peripheral rim enhancement and mass-like enlargement decreased concomitantly on CT images (p < 0.001). Conclusion: CT may be helpful in diagnosing adrenal tuberculosis when clinically suspected, and CT features are correlated to the clinical duration of Addison's disease

  14. Assessment of inflammatory activity in Crohn's disease by means of dynamic contrast-enhanced MRI.

    Science.gov (United States)

    Pupillo, V A; Di Cesare, E; Frieri, G; Limbucci, N; Tanga, M; Masciocchi, C

    2007-09-01

    Our aim was to perform a dynamic study of contrast enhancement of the intestinal wall in patients with Crohn's disease to quantitatively assess local inflammatory activity. We studied a population of 50 patients with histologically proven Crohn's disease. Magnetic resonance imaging (MRI) was performed using a 1.5-T magnet with a phased-array coil and acquisition of T2-weighted single-shot fast spin echo (SSFSE) half Fourier sequences before intravenous administration of gadolinium, and T1-weighted fast spoiled gradient (FSPGR) fat-saturated sequences before and after contrast administration. Before the examination, patents received oral polyethylene glycol (PEG) (1,000 ml for adults; 10 ml/Kg of body weight for children). Regions of interest (ROI) were placed on the normal and diseased intestinal wall to assess signal intensity and rate of increase in contrast enhancement over time. Data were compared with the Crohn's Disease Activity Index (CDAI). The diseased bowel wall showed early and intense uptake of contrast that increases over time until a plateau is reached. In patients in the remission phase after treatment, signal intensity was only slightly higher in diseased bowel loops than in healthy loops. There was a significant correlation between the peak of contrast uptake and CDAI. Dynamic MRI is a good technique for quantifying local inflammatory activity of bowel wall in patients with Crohn's disease.

  15. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure

    International Nuclear Information System (INIS)

    Jessop, Forrest; Hamilton, Raymond F.; Rhoderick, Joseph F.; Shaw, Pamela K.; Holian, Andrij

    2016-01-01

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5 fl/fl LysM-Cre + mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5 fl/fl LysM-Cre + mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis. - Highlights: • Silica exposure increases autophagy in macrophages. • Autophagy deficient mice have enhanced inflammation and silicosis. • Autophagy deficiency in macrophages results in greater silica-induced cytotoxicity. • Autophagy deficiency in macrophages increases extracellular IL-18 and HMGB1.

  16. Companion cropping with potato onion enhances the disease resistance of tomato against Verticillium dahliae

    Directory of Open Access Journals (Sweden)

    Xuepeng eFu

    2015-09-01

    Full Text Available Intercropping could alleviate soil-borne diseases, however, few studies focused on the immunity of the host plant induced by the interspecific interactions. To test whether or not intercropping could enhance the disease resistance of host plant, we investigated the effect of companion cropping with potato onion on tomato Verticillium wilt caused by Verticillium dahliae (V. dahliae. To investigate the mechanisms, the root exudates were collected from tomato and potato onion which were grown together or separately, and were used to examine the antifungal activities against V. dahliae in vitro, respectively. Furthermore, RNA-seq was used to examine the expression pattern of genes related to disease resistance in tomato companied with potato onion compared to that in tomato grown alone, under the condition of infection with V. dahliae. The results showed that companion cropping with potato onion could alleviate the incidence and severity of tomato Verticillium wilt. The further studies revealed that the root exudates from tomato companied with potato onion significantly inhibited the mycelia growth and spore germination of V. dahliae. However, there were no significant effects on these two measurements for the root exudates from potato onion grown alone or from potato onion grown with tomato. RNA-seq data analysis showed the disease defense genes associated with pathogenesis-related proteins, biosynthesis of lignin, hormone metabolism and signal transduction were expressed much higher in the tomato companied with potato onion than those in the tomato grown alone, which indicated that these defense genes play important roles in tomato against V. dahliae infection, and meant that the disease resistance of tomato against V. dahliae was enhanced in the companion copping with potato onion. We proposed that companion cropping with potato onion could enhance the disease resistance of tomato against V. dahliae by regulating the expression of genes related

  17. Feasibility of gadoxetate disodium-enhanced MR cholangiography in chronic cholestatic biliary disease

    International Nuclear Information System (INIS)

    Kühn, J.-P.; Spoerl, M.; Nassif, A.; Mester, M.; Weitschies, W.; Siegmund, W.; Hosten, N.; Mensel, B.

    2014-01-01

    Aim: To investigate the feasibility of gadoxetate disodium-enhanced magnetic resonance (MR) cholangiography in chronic obstructive cholestatic biliary disease in the clinical setting. Materials and methods: Twenty-three patients with dilated bile duct trees and ten volunteers underwent gadoxetate disodium-enhanced liver MR cholangiography and were enrolled in the present retrospective study. Gadoxetate disodium was given in a standardized manner as a bolus injection at a dose of 0.25 mmol/kg of body weight (0.1 ml/kg). Region of interest-based measurement of mean enhancement of the dilated bile ducts was performed in series before gadoxetate disodium administration and during hepatobiliary phases. Results: Direct comparison of mean bile duct enhancement during hepatobiliary phases in the clinical imaging window between healthy volunteers [4.7 ± 2.2 arbitrary units (au)] and patients with dilated bile ducts (0.1 ± 0.3 au) revealed significantly lower or absent enhancement in dilated bile ducts (p = 0.001). Conclusion: Standard clinical gadoxetate disodium-enhanced MR cholangiography is not a reliable technique for the evaluation of the biliary trees, because of altered biliary gadoxetate disodium elimination in patients with chronic obstructive biliary diseases. - Highlights: • Biliary excretion of gadoxetic disodium is impaired in subjects with chronic central or segmental bile duct obstruction. • MR cholangiography using gadoxetic disodium is not feasible in patients with chronic cholestatic bile duct disease. • Gadoxetic disodium enhanced MRI is a potential biomarker to measure hepatobiliary transporter function

  18. Interventions to enhance work participation of workers with a chronic disease: a systematic review of reviews.

    Science.gov (United States)

    Vooijs, Marloes; Leensen, Monique C J; Hoving, Jan L; Wind, Haije; Frings-Dresen, Monique H W

    2015-11-01

    The aim of this systematic review was to provide an overview of the available effective interventions that enhance work participation of people with a chronic disease, irrespective of their diagnosis. A search was conducted in PubMed, EMBASE, PsycINFO, CINAHL and the Cochrane Library, searching for systematic reviews published between 2004 and February 2015. Systematic reviews were eligible for inclusion if they described an intervention aimed at enhancing work participation and included participants of working age (18-65 years) with a chronic disease. Reviews had to include populations having different chronic diseases. The quality of the included reviews was evaluated using the quality instrument AMSTAR. Results of reviews of medium and high quality were described in this review. The search resulted in 9 reviews, 5 of which were of medium quality. No high quality reviews were retrieved. 1 review reported inconclusive evidence for policy-based return to work initiatives. The 4 other reviews described interventions focused on changes at work, such as changes in work organisation, working conditions and work environment. Of these 4 reviews, 3 reported beneficial effects of the intervention on work participation. Interventions examined in populations having different chronic diseases were mainly focused on changes at work. The majority of the included interventions were reported to be effective in enhancing work participation of people with a chronic disease, indicating that interventions directed at work could be considered for a generic approach in order to enhance work participation in various chronic diseases. 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.

  19. Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Tsubakimoto, Maho [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nakagami-Gun, Okinawa (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

    2014-02-15

    Purpose: To prospectively and directly compare oxygen-enhanced (O{sub 2}-enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O{sub 2}-enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O{sub 2}-enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O{sub 2}-enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD.

  20. Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

    International Nuclear Information System (INIS)

    Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Tsubakimoto, Maho; Sugimura, Kazuro

    2014-01-01

    Purpose: To prospectively and directly compare oxygen-enhanced (O 2 -enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O 2 -enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O 2 -enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O 2 -enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD

  1. Brightness-preserving fuzzy contrast enhancement scheme for the detection and classification of diabetic retinopathy disease.

    Science.gov (United States)

    Datta, Niladri Sekhar; Dutta, Himadri Sekhar; Majumder, Koushik

    2016-01-01

    The contrast enhancement of retinal image plays a vital role for the detection of microaneurysms (MAs), which are an early sign of diabetic retinopathy disease. A retinal image contrast enhancement method has been presented to improve the MA detection technique. The success rate on low-contrast noisy retinal image analysis shows the importance of the proposed method. Overall, 587 retinal input images are tested for performance analysis. The average sensitivity and specificity are obtained as 95.94% and 99.21%, respectively. The area under curve is found as 0.932 for the receiver operating characteristics analysis. The classifications of diabetic retinopathy disease are also performed here. The experimental results show that the overall MA detection method performs better than the current state-of-the-art MA detection algorithms.

  2. Dimethyloxalylglycine may be enhance the capacity of neural-like cells in treatment of Alzheimer disease.

    Science.gov (United States)

    Ghasemi Moravej, Fahimeh; Vahabian, Mehrangiz; Soleimani Asl, Sara

    2016-06-01

    Although using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats. © 2016 International Federation for Cell Biology.

  3. Cognitive enhancers (Nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. Disease-modifying drugs. Update 2014.

    Science.gov (United States)

    Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

    2014-01-01

    Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers, are very productive. The review "Drugs interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs" was accepted in October 2012. In the last 20 months, new targets for the potential treatment of Alzheimer's disease were identified. Enormous progress was realized in the pharmacological characterization of natural products with cognitive enhancing properties. This review covers the evolution of research in this field through May 2014.

  4. Enhancing chronic disease management: a review of key issues and strategies.

    Science.gov (United States)

    Willison, Kevin D; Williams, Paul; Andrews, Gavin J

    2007-11-01

    This paper highlights three selected issues and potential strategies towards meeting chronic disease management needs. First, the orientation of the biomedical science model often gives insufficient attention to chronic health care needs. A second issue is that the use of complementary and alternative medicine (CAM) may offer for some an opportunity to enhance their chronic disease management efforts. A third issue is that our understanding of this potential is limited, as many who use CAM do not disclose such use. With reference to proposed solutions/strategies, first, an improved focus to respect patient/client values and goals may encourage people to disclose their use of CAM. Second, a community-based participatory approach shows promise in enhancing communication plus helps integrate CAM within new models of chronic disease management. Lastly, those in public health could help facilitate such an approach plus be a monitor of CAM practices. Overall, this review provides a springboard for further research and practice in CAM and the management of chronic diseases.

  5. Automated Detection of Healthy and Diseased Aortae from Images Obtained by Contrast-Enhanced CT Scan

    Directory of Open Access Journals (Sweden)

    Michael Gayhart

    2013-01-01

    Full Text Available Purpose. We developed the next stage of our computer assisted diagnosis (CAD system to aid radiologists in evaluating CT images for aortic disease by removing innocuous images and highlighting signs of aortic disease. Materials and Methods. Segmented data of patient’s contrast-enhanced CT scan was analyzed for aortic dissection and penetrating aortic ulcer (PAU. Aortic dissection was detected by checking for an abnormal shape of the aorta using edge oriented methods. PAU was recognized through abnormally high intensities with interest point operators. Results. The aortic dissection detection process had a sensitivity of 0.8218 and a specificity of 0.9907. The PAU detection process scored a sensitivity of 0.7587 and a specificity of 0.9700. Conclusion. The aortic dissection detection process and the PAU detection process were successful in removing innocuous images, but additional methods are necessary for improving recognition of images with aortic disease.

  6. The analysis of the contrast enhanced lesions on cerebro-vascular diseases

    International Nuclear Information System (INIS)

    Terada, Tomoaki; Nishiguchi, Takashi; Hyoutani, Genhachi; Miyamoto, Kazuki; Komai, Norihiko

    1989-01-01

    The contrast enhancement of cerebro-vascular diseases on CT is thought to be due to the increase of the cerebral blood volume (CBV) and/or the disruption of the blood brain barrier (BBB). However, it is difficult to differentiate these two conditions only by contrast enhanced CT. We employed dynamic CT (DCT) to analyse these lesions with respect to the patterns of time-density curve and peak height (PH) of the curve upon the theoretical basis that flattening of the latter part of the time-density curve reflected the degree of BBB disruption and PH reflected the CBV. In all cases of hypertensive intracerebral hemorrhage (11 cases), the contrast enhanced lesion around the hematoma showed marked BBB disruption according to the results of DCT. In 11 cases of cerebral infarction, patterns of BBB disruption and CBV varied at the contrast enhanced lesions according to the result of DCT. However, all contrast enhanced lesions with increased PH were associated with hemorrhagic infarction. Thus, the precise analysis of DCT provides appropriate therapeutic schedules by predicting the occurrence of hemorrhagic infarction. (author)

  7. Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

    Science.gov (United States)

    Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

    2017-09-15

    Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

  8. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game.

    Science.gov (United States)

    van der Sanden, Sabine M G; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C; Brooks, Paula; O'Donnell, Jason; Jones, Les P; Brown, Cedric; Tompkins, S Mark; Oberste, M Steven; Karpilow, Jon; Tripp, Ralph A

    2016-02-15

    Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work

  9. A review of the use of engineered nanomaterials to suppress plant disease and enhance crop yield

    International Nuclear Information System (INIS)

    Servin, Alia; Elmer, Wade; Mukherjee, Arnab; Torre-Roche, Roberto De la; Hamdi, Helmi; White, Jason C.; Bindraban, Prem; Dimkpa, Christian

    2015-01-01

    Nanotechnology has the potential to play a critical role in global food production, food security, and food safety. The applications of nanotechnology in agriculture include fertilizers to increase plant growth and yield, pesticides for pest and disease management, and sensors for monitoring soil quality and plant health. Over the past decade, a number of patents and products incorporating nanomaterials into agricultural practices (e.g., nanopesticides, nanofertilizers, and nanosensors) have been developed. The collective goal of all of these approaches is to enhance the efficiency and sustainability of agricultural practices by requiring less input and generating less waste than conventional products and approaches. This review evaluates the current literature on the use of nanoscale nutrients (metals, metal oxides, carbon) to suppress crop disease and subsequently enhance growth and yield. Notably, this enhanced yield may not only be directly linked to the reduced presence of pathogenic organisms, but also to the potential nutritional value of the nanoparticles themselves, especially for the essential micronutrients necessary for host defense. We also posit that these positive effects are likely a result of the greater availability of the nutrients in the “nano” form. Last, we offer comments on the current regulatory perspective for such applications

  10. A review of the use of engineered nanomaterials to suppress plant disease and enhance crop yield

    Energy Technology Data Exchange (ETDEWEB)

    Servin, Alia; Elmer, Wade; Mukherjee, Arnab; Torre-Roche, Roberto De la [The Connecticut Agricultural Experiment Station (United States); Hamdi, Helmi [University of Carthage, Water Research and Technology Center (Tunisia); White, Jason C., E-mail: jason.white@ct.gov [The Connecticut Agricultural Experiment Station (United States); Bindraban, Prem; Dimkpa, Christian [Virtual Fertilizer Research Center (United States)

    2015-02-15

    Nanotechnology has the potential to play a critical role in global food production, food security, and food safety. The applications of nanotechnology in agriculture include fertilizers to increase plant growth and yield, pesticides for pest and disease management, and sensors for monitoring soil quality and plant health. Over the past decade, a number of patents and products incorporating nanomaterials into agricultural practices (e.g., nanopesticides, nanofertilizers, and nanosensors) have been developed. The collective goal of all of these approaches is to enhance the efficiency and sustainability of agricultural practices by requiring less input and generating less waste than conventional products and approaches. This review evaluates the current literature on the use of nanoscale nutrients (metals, metal oxides, carbon) to suppress crop disease and subsequently enhance growth and yield. Notably, this enhanced yield may not only be directly linked to the reduced presence of pathogenic organisms, but also to the potential nutritional value of the nanoparticles themselves, especially for the essential micronutrients necessary for host defense. We also posit that these positive effects are likely a result of the greater availability of the nutrients in the “nano” form. Last, we offer comments on the current regulatory perspective for such applications.

  11. How glyphosate affects plant disease development: it is more than enhanced susceptibility.

    Science.gov (United States)

    Hammerschmidt, Ray

    2018-05-01

    Glyphosate has been shown to affect the development of plant disease in several ways. Plants utilize phenolic and other shikimic acid pathway-derived compounds as part of their defense against pathogens, and glyphosate inhibits the biosynthesis of these compounds via its mode of action. Several studies have shown a correlation between enhanced disease and suppression of phenolic compound production after glyphosate. Glyphosate-resistant crop plants have also been studied for changes in resistance as a result of carrying the glyphosate resistance trait. The evidence indicates that neither the resistance trait nor application of glyphosate to glyphosate-resistant plants increases susceptibility to disease. The only exceptions to this are cases where glyphosate has been shown to reduce rust diseases on glyphosate-resistant crops, supporting a fungicidal role for this chemical. Finally, glyphosate treatment of weeds or volunteer crops can cause a temporary increase in soil-borne pathogens that may result in disease development if crops are planted too soon after glyphosate application. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Enhancing biological control of basal stem rot disease (Ganoderma boninense) in oil palm plantations.

    Science.gov (United States)

    Susanto, A; Sudharto, P S; Purba, R Y

    2005-01-01

    Basal Stem Rot (BSR) disease caused by Ganoderma boninense is the most destructive disease in oil palm, especially in Indonesia and Malaysia. The available control measures for BSR disease such as cultural practices and mechanical and chemical treatment have not proved satisfactory due to the fact that Ganoderma has various resting stages such as melanised mycelium, basidiospores and pseudosclerotia. Alternative control measures to overcome the Ganoderma problem are focused on the use of biological control agents and planting resistant material. Present studies conducted at Indonesian Oil Palm Research Institute (IOPRI) are focused on enhancing the use of biological control agents for Ganoderma. These activities include screening biological agents from the oil palm rhizosphere in order to evaluate their effectiveness as biological agents in glasshouse and field trials, testing their antagonistic activities in large scale experiments and eradicating potential disease inoculum with biological agents. Several promising biological agents have been isolated, mainly Trichoderma harzianum, T. viride, Gliocladium viride, Pseudomonas fluorescens, and Bacillus sp. A glasshouse and field trial for Ganoderma control indicated that treatment with T. harzianum and G. viride was superior to Bacillus sp. A large scale trial showed that the disease incidence was lower in a field treated with biological agents than in untreated fields. In a short term programme, research activities at IOPRI are currently focusing on selecting fungi that can completely degrade plant material in order to eradicate inoculum. Digging holes around the palm bole and adding empty fruit bunches have been investigated as ways to stimulate biological agents.

  13. 3D-shaded surface rendering of gadolinium-enhanced MR angiography in congenital heart disease

    International Nuclear Information System (INIS)

    Okuda, S.; Kikinis, R.; Dumanli, H.; Geva, T.; Powell, A.J.; Chung, T.

    2000-01-01

    Background. Gadolinium-enhanced three-dimensional (3D) MR angiography is a useful imaging technique for patients with congenital heart disease. Objective. This study sought to determine the added value of creating 3D shaded surface displays compared to standard maximal intensity projection (MIP) and multiplanar reformatting (MPR) techniques when analyzing 3D MR angiography data. Materials and methods. Seventeen patients (range, 3 months to 51 years old) with a variety of congenital cardiovascular defects underwent gadolinium-enhanced 3D MR angiography of the thorax. Color-coded 3D shaded surface models were rendered from the image data using manual segmentation and computer-based algorithms. Models could be rotated, translocated, or zoomed interactively by the viewer. Information available from the 3D models was compared to analysis based on viewing standard MIP/MPR displays. Results. Median postprocessing time for the 3D models was 6 h (range, 3-25 h) compared to approximately 20 min for MIP/MPR viewing. No additional diagnostic information was gained from 3D model analysis. All major findings with MIP/MPR postprocessing were also apparent on the 3D models. Qualitatively, the 3D models were more easily interpreted and enabled adjacent vessels to be distinguished more readily. Conclusion. Routine use of 3D shaded surface reconstructions for visualization of contrast enhanced MR angiography in congenital heart disease cannot be recommended. 3D surface rendering may be more useful for presenting complex anatomy to an audience unfamiliar with congenital heart disease and as an educational tool. (orig.)

  14. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium.

    Science.gov (United States)

    Moon, James C C; Sachdev, Bhavesh; Elkington, Andrew G; McKenna, William J; Mehta, Atul; Pennell, Dudley J; Leed, Philip J; Elliott, Perry M

    2003-12-01

    Anderson-Fabry Disease (AFD), an X-linked disorder of sphingolipid metabolism, is a cause of idiopathic left ventricular hypertrophy but the mechanism of hypertrophy is poorly understood. Gadolinium enhanced cardiovascular magnetic resonance can detect focal myocardial fibrosis. We hypothesised that hyperenhancement would be present in AFD. Eighteen males (mean 43+/-14 years) and eight female heterozygotes (mean 48+/-12 years) with AFD underwent cine and late gadolinium cardiovascular magnetic resonance. Nine male (50%) had myocardial hyperenhancement ranging from 3.4% to 20.6% (mean 7.7+/-5.7%) of total myocardium; in males, percentage hyperenhancement related to LV mass index (r=0.78, P=0.0002) but not to ejection fraction or left ventricular volumes. Lesser hyperenhancement was also found in four (50%) heterozygous females (mean 4.6%). In 12 (92%) patients with abnormal gadolinium uptake, hyperenhancement occurred in the basal infero-lateral wall where, unlike myocardial infarction, it was not sub-endocardial. In two male patients with severe LVH (left ventricular hypertrophy) and systolic impairment there was additional hyperenhancement in other myocardial segments. These observations suggests that myocardial fibrosis occurs in AFD and may contribute to the hypertrophy and the natural history of the disease.

  15. Investigating the enhancing effect of music on autobiographical memory in mild Alzheimer's disease.

    Science.gov (United States)

    Irish, Muireann; Cunningham, Conal J; Walsh, J Bernard; Coakley, Davis; Lawlor, Brian A; Robertson, Ian H; Coen, Robert F

    2006-01-01

    The enhancing effect of music on autobiographical memory recall in mild Alzheimer's disease individuals (n = 10; Mini-Mental State Examination score >17/30) and healthy elderly matched individuals (n = 10; Mini-Mental State Examination score 25-30) was investigated. Using a repeated-measures design, each participant was seen on two occasions: once in music condition (Vivaldi's 'Spring' movement from 'The Four Seasons') and once in silence condition, with order counterbalanced. Considerable improvement was found for Alzheimer individuals' recall on the Autobiographical Memory Interview in the music condition, with an interaction for condition by group (p music condition (p music on autobiographical memory recall.

  16. Familiar Music as an Enhancer of Self-Consciousness in Patients with Alzheimer's Disease

    Science.gov (United States)

    Arroyo-Anlló, Eva M.; Díaz, Juan Poveda; Gil, Roger

    2013-01-01

    The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC) in patients with Alzheimer's disease (AD). For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspection and moral judgments. One AD group received familiar music stimulation and another AD group unfamiliar music stimulation over three months. The AD patients who received a familiar music intervention showed a stabilization or improvement in aspects of SC. By contrast, control AD group showed a deterioration of most of the SC aspects after unfamiliar music stimulation, except the SC aspects of body representation and affective state. Familiar music stimulation could be considered as an enhancer of SC in patients with Alzheimer's disease. PMID:24106716

  17. Familiar Music as an Enhancer of Self-Consciousness in Patients with Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Eva M. Arroyo-Anlló

    2013-01-01

    Full Text Available The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC in patients with Alzheimer’s disease (AD. For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspection and moral judgments. One AD group received familiar music stimulation and another AD group unfamiliar music stimulation over three months. The AD patients who received a familiar music intervention showed a stabilization or improvement in aspects of SC. By contrast, control AD group showed a deterioration of most of the SC aspects after unfamiliar music stimulation, except the SC aspects of body representation and affective state. Familiar music stimulation could be considered as an enhancer of SC in patients with Alzheimer’s disease.

  18. Familiar music as an enhancer of self-consciousness in patients with Alzheimer's disease.

    Science.gov (United States)

    Arroyo-Anlló, Eva M; Díaz, Juan Poveda; Gil, Roger

    2013-01-01

    The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC) in patients with Alzheimer's disease (AD). For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspection and moral judgments. One AD group received familiar music stimulation and another AD group unfamiliar music stimulation over three months. The AD patients who received a familiar music intervention showed a stabilization or improvement in aspects of SC. By contrast, control AD group showed a deterioration of most of the SC aspects after unfamiliar music stimulation, except the SC aspects of body representation and affective state. Familiar music stimulation could be considered as an enhancer of SC in patients with Alzheimer's disease.

  19. Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

    Directory of Open Access Journals (Sweden)

    Ganapati V Hegde

    Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

  20. Contrast enhancement by arterial perfusion during computed tomography (computed tomographic arteriography) of the pancreatic disease

    International Nuclear Information System (INIS)

    Takaki, Yukiari

    1983-01-01

    Computed tomographic arteriography (CTA) was performed on 52 cases of pancreatic disease in which was suspected clinically, and in which other method failed to yield a definitive diagnosis. For CTA, 65% meglumine diatrizoate 20 ml, diluted 1:3, was injected via a catherter inserted in an artery connected with the pancreas and the change with time of the pacreas CT number was studied. The normal pancreas stains deeply and the best contrast enhancement was obtained between 17 to 21 seconds after instillation of contrast medium. In the CTA findings in pancreatic cancer, low density areas with irregular internal structures are characteristic, and these characteristics were seen even in minute pancreatic cancers which could not be recognized by CT or the intravenous bolus injection method. On the other hand, in chronic pancreatitis, even when differentiation from pancreatic cancer is difficult with arterial and venous encasement in angiography, as long as the chronic pancreatitis is not very advanced ischemic changes are not seen, and this permits differentiation form normal pancreas. This also facilitates differentiation between pancreatitis and pancreatic cancer. In the intravenous bolus injection method, the chronological change of contrast enhancement in the pancreas was studied and the best contrast enhancement was obtained after 60 to 120 seconds. This method revealed no findings peculiar to pancreatic cancer. Based on the above, CTA was found to be useful for making in contributing to establishing a definitive diagnosis, detecting minute pancreatic cancer and to differentiate pancreatic cancer from chronic pancreatitis. (author)

  1. Conceptualizing how group singing may enhance quality of life with Parkinson's disease.

    Science.gov (United States)

    Buetow, Stephen A; Talmage, Alison; McCann, Clare; Fogg, Laura; Purdy, Suzanne

    2014-01-01

    Abstract Purpose: Group singing could be a promising component of neurorehabilitative care. This article aims to conceptualize how group singing may enable people with Parkinson's disease (PD) to synchronize their movement patterns to musical rhythm and enhance quality of life. Spanning the medical and social sciences, the article draws conceptually on literature on PD, group singing and rhythm in music; personal experience; and reasoning. Conceptualizing PD in terms of disruptions to social and biological rhythms, we hypothesize how group singing may produce two socio-psychological states - connectedness and flow - that may entrain rhythm in people with PD. The states connect during group singing to elicit and enhance motor processes but may also reawaken after the group singing, through the recall and reactivation of the musical rhythms encoded during group singing. In people with PD, this continuity of flow is hypothesized to be conducive to rhythmic entrainment during and after group singing and in turn to reduced deficits in motor timing and emotional processing, and improvements in quality of life. Empirical studies are needed to test this hypothesis in people with movement disorders such as PD. Implications for Rehabilitation Musical rhythm in group singing may enhance quality of life, and rehabilitation, in people with PD. Use group singing to produce two socio-psychological states - connectedness and flow - that may yield these health benefits. Include people with PD in singing groups to facilitate perceptual exposure to familiar music with melodic distinctiveness and a regular beat.

  2. Evaluation of conventional, dynamic contrast enhanced and diffusion weighted MRI for quantitative Crohn's disease assessment with histopathology of surgical specimens

    NARCIS (Netherlands)

    Tielbeek, Jeroen A. W.; Ziech, Manon L. W.; Li, Zhang; Lavini, Cristina; Bipat, Shandra; Bemelman, Willem A.; Roelofs, Joris J. T. H.; Ponsioen, Cyriel Y.; Vos, Frans M.; Stoker, Jaap

    2014-01-01

    To prospectively compare conventional MRI sequences, dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging (DWI) with histopathology of surgical specimens in Crohn's disease. 3-T MR enterography was performed in consecutive Crohn's disease patients scheduled for surgery within 4 weeks.

  3. Enhanced Arabidopsis disease resistance against Botrytis cinerea induced by sulfur dioxide.

    Science.gov (United States)

    Xue, Meizhao; Yi, Huilan

    2018-01-01

    Sulfur dioxide (SO 2 ) is a common air pollutant that has complex impacts on plants. The effect of prior exposure to 30mgm -3 SO 2 on defence against Botrytis cinerea (B. cinerea) in Arabidopsis thaliana and the possible mechanisms of action were investigated. The results indicated that pre-exposure to 30mgm -3 SO 2 resulted in significantly enhanced resistance to B. cinerea infection. SO 2 pre-treatment significantly enhanced the activities of defence-related enzymes including phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), β-1,3-glucanase (BGL) and chitinase (CHI). Transcripts of the defence-related genes PAL, PPO, PR2, and PR3, encoding PAL, PPO, BGL and CHI, respectively, were markedly elevated in Arabidopsis plants pre-exposed to SO 2 and subsequently inoculated with B. cinerea (SO 2 + treatment group) compared with those that were only treated with SO 2 (SO 2 ) or inoculated with B. cinerea (CK+). Moreover, SO 2 pre-exposure also led to significant increases in the expression levels of MIR393, MIR160 and MIR167 in Arabidopsis. Meanwhile, the expression of known targets involved in the auxin signalling pathway, was negatively correlated with their corresponding miRNAs. Additionally, the transcript levels of the primary auxin-response genes GH3-like, BDL/IAA12, and AXR3/IAA17 were markedly repressed. Our findings indicate that 30mgm -3 SO 2 pre-exposure enhances disease resistance against B. cinerea in Arabidopsis by priming defence responses through enhancement of defence-related gene expression and enzyme activity, and miRNA-mediated suppression of the auxin signalling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease

    Energy Technology Data Exchange (ETDEWEB)

    Beslow, Lauren A.; Boennemann, Carsten G. [Children' s Hospital of Philadelphia, Division of Neurology, Philadelphia, PA (United States); Schwartz, Erin S. [Children' s Hospital of Philadelphia, Division of Neuroradiology, Philadelphia, PA (United States)

    2008-06-15

    We present serial MR findings in a child ultimately diagnosed with the early infantile form of Krabbe disease. MR showed typical features of Krabbe disease including cerebellar and brainstem hyperintensity, periventricular and deep white matter hyperintensity, and cerebral atrophy. In addition, the combination of both enlargement and enhancement of multiple cranial nerves in conjunction with unusual cystic lesions adjacent to the frontal horns of the lateral ventricles was previously unreported and expands the spectrum of imaging findings in early Krabbe disease. (orig.)

  5. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease

    OpenAIRE

    Moon, J. C.; Sheppard, M.; Reed, E.; Lee, P.; Elliott, P. M.; Pennell, D. J.

    2006-01-01

    Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic d...

  6. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Horas H Nababan, Saut; Nishiumi, Shin; Kawano, Yuki; Kobayashi, Takashi; Yoshida, Masaru; Azuma, Takeshi

    2017-06-01

    This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Larson, Janet L; Covey, Margaret K; Kapella, Mary C; Alex, Charles G; McAuley, Edward

    2014-01-01

    People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. IN THIS RANDOMIZED CONTROLLED TRIAL, SUBJECTS WERE ASSIGNED TO: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR), health education with upper body resistance training (ED-UBR), or health education with gentle chair exercises (ED-Chair). Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Differences were observed in light physical activity (LPA) after 4 months of training, time by group interaction effect (P=0.045). The SE-UBR group increased time spent in LPA by +20.68±29.30 minutes/day and the other groups decreased time spent in LPA by -22.43±47.88 minutes/day and -25.73±51.76 minutes/day. Changes in LPA were not sustained at 12-month follow-up. There were no significant changes in moderate-to-vigorous physical activity, sedentary time, or functional performance. Subjects spent most of their waking hours sedentary: 72%±9% for SE-UBR, 68%±10% for ED-UBR, and 74%±9% for ED-Chair. The self-efficacy enhancing intervention produced a modest short-term increase in LPA. Further work is needed to increase the magnitude and duration of effect, possibly by targeting LPA.

  8. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

    Science.gov (United States)

    Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

    2015-09-29

    The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression

    Directory of Open Access Journals (Sweden)

    Janneke G.C. Peeters

    2015-09-01

    Full Text Available The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4+ memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases.

  10. Non-communicable diseases and global health governance: enhancing global processes to improve health development.

    Science.gov (United States)

    Magnusson, Roger S

    2007-05-22

    This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO), World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control), but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health). The paper assesses the merits of the Millennium Development Goals (MDGs) and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy.

  11. Non-communicable diseases and global health governance: enhancing global processes to improve health development

    Directory of Open Access Journals (Sweden)

    Magnusson Roger S

    2007-05-01

    Full Text Available Abstract This paper assesses progress in the development of a global framework for responding to non-communicable diseases, as reflected in the policies and initiatives of the World Health Organization (WHO, World Bank and the UN: the institutions most capable of shaping a coherent global policy. Responding to the global burden of chronic disease requires a strategic assessment of the global processes that are likely to be most effective in generating commitment to policy change at country level, and in influencing industry behaviour. WHO has adopted a legal process with tobacco (the WHO Framework Convention on Tobacco Control, but a non-legal, advocacy-based approach with diet and physical activity (the Global Strategy on Diet, Physical Activity and Health. The paper assesses the merits of the Millennium Development Goals (MDGs and the FCTC as distinct global processes for advancing health development, before considering what lessons might be learned for enhancing the implementation of the Global Strategy on Diet. While global partnerships, economic incentives, and international legal instruments could each contribute to a more effective global response to chronic diseases, the paper makes a special case for the development of international legal standards in select areas of diet and nutrition, as a strategy for ensuring that the health of future generations does not become dependent on corporate charity and voluntary commitments. A broader frame of reference for lifestyle-related chronic diseases is needed: one that draws together WHO's work in tobacco, nutrition and physical activity, and that envisages selective use of international legal obligations, non-binding recommendations, advocacy and policy advice as tools of choice for promoting different elements of the strategy.

  12. Pictures as a neurological tool: lessons from enhanced and emergent artistry in brain disease.

    Science.gov (United States)

    Schott, G D

    2012-06-01

    Pictures created spontaneously by patients with brain disease often display impaired or diminished artistry, reflecting the patient's cerebral damage. This article explores the opposite: those pictures created in the face of brain disease that show enhanced or enduring artistry, and those that emerge for the first time in artistically naïve patients. After comments on background issues relating to the patient and the viewer, the paintings and drawings are considered in relation to the heterogeneous conditions in which this artistic creativity is seen. These conditions include various dementias-most notably frontotemporal lobar dementia, stroke, Parkinson's disease, autism and related disorders and psychiatric disease, epilepsy, migraine and trauma. In the discussion, it is argued that evidence of underlying brain dysfunction revealed by these pictures often rests on the abnormal context in which the pictures are created, or on changes in artistry demonstrated by a sequence of pictures. In the former, the compulsive element and sensory and emotional accompaniments are often important features; in the latter, evolving changes are evident, and have included depiction of increasing menace in portrayal of faces. The occurrence of synaesthesia, and its relation to creativity, are briefly discussed in respect of two unusual patients, followed by considering the role of the anterior and frontal lobes, mesolimbic connections and the right hemisphere. In at least some patients, impaired inhibition leading to paradoxical functional facilitation, with compensatory changes particularly in the right posterior hemisphere, is likely to be pivotal in enabling unusual artistry to emerge; preservation of language, however, is not a prerequisite. Many patients studied have been artists, and it appears possible that some of those with an artistic predisposition may be more likely to experience pathologically obsessive creativity. The discussion concludes that occasionally pictures

  13. Dynamic contrast-enhanced 3-T magnetic resonance imaging: a method for quantifying disease activity in early polyarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Navalho, Marcio [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital da Luz, Radiology Department, Lisbon (Portugal); Hospital da Luz, Centro de Imagiologia, Lisbon (Portugal); Resende, Catarina [Hospital da Luz, Rheumatology Department, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Rodrigues, Ana Maria; Fonseca, Joao Eurico; Canhao, Helena [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Gaspar, Augusto [Hospital da Luz, Radiology Department, Lisbon (Portugal); Campos, Jorge [Hospital de Santa Maria, Radiology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal)

    2012-01-15

    To determine whether measurement of synovial enhancement and thickness quantification parameters with 3.0-Tesla magnetic resonance imaging (3-T MRI) can reliably quantify disease activity in patients with early polyarthritis. Eighteen patients (16 women, 2 men; mean age 46 years) with early polyarthritis with less than 12 months of symptoms were included. MRI examination using 3-T device was performed by a new approach including both wrists and hands simultaneously in the examination field-of-view. MRI scoring of disease activity included quantification of synovial enhancement with simple measurements such as rate of early enhancement (REE; REE{sub 57} = S{sub 57}/S{sub 200}, where S{sub 57} and S{sub 200} are the signal intensities 57 s and 200 s after gadolinium injection) and rate of relative enhancement (RE; RE = S{sub 200} - S{sub 0}). Both wrists and hands were scored according to the Rheumatoid Arthritis MRI Scoring System (RAMRIS) for synovitis. Disease activity was clinically assessed by the 28-joint Disease Activity Score (DAS28). DAS28 score was strongly correlated with RE (r = 0.8331, p < 0.0001), REE (r = 0.8112, p < 0.0001), and RAMRIS score for synovitis (r = 0.7659, p < 0.0002). An REE score above 0.778 accurately identified patients with clinically active disease (sensitivity 92%; specificity 67%; p < 0.05). A statistically significant difference was observed in the RE, REE, and RAMRIS scores for synovitis between patients with active and inactive disease (p < 0.05). Our findings support the use of 3-T dynamic contrast-enhanced MRI for precise quantification of disease activity and for discriminating active disease from inactive disease in early polyarthritis. (orig.)

  14. Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Susann Lehmann

    2017-02-01

    Full Text Available Familial forms of Parkinson's disease (PD caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD+ is essential for both generating energy in mitochondria and nuclear DNA repair through NAD+-consuming poly(ADP-ribose polymerases (PARPs. We found alterations in NAD+ salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD+ precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration. Additionally, a mutation of Parp improved mitochondrial function and was neuroprotective in the pink1 mutants. We conclude that enhancing the availability of NAD+ by either the use of a diet supplemented with NAD+ precursors or the inhibition of NAD+-dependent enzymes, such as PARPs, which compete with mitochondria for NAD+, is a viable approach to preventing neurotoxicity associated with mitochondrial defects.

  15. Contrast-enhanced ultrasound evaluation of hepatic microvascular changes in liver diseases.

    Science.gov (United States)

    Ridolfi, Francesco; Abbattista, Teresa; Busilacchi, Paolo; Brunelli, Eugenio

    2012-10-07

    To assess if software assisted-contrast-enhanced ultrasonography (CEUS) provides reproducible perfusion parameters of hepatic parenchyma in patients affected by chronic liver disease. Forty patients with chronic viral liver disease, with (n = 20) or without (n = 20) cirrhosis, and 10 healthy subjects underwent CEUS and video recordings of each examination were then analysed with Esaote's Qontrast software. CEUS dedicated software Qontrast was used to determine peak (the maximum signal intensity), time to peak (TTP), region of blood value (RBV) proportional to the area under the time-intensity curve, mean transit time (MTT) measured in seconds and region of blood flow (RBF). Qontrast-assisted CEUS parameters displayed high inter-observer reproducibility (κ coefficients of 0.87 for MTT and 0.90 TTP). When the region of interest included a main hepatic vein, Qontrast-calculated TTP was significantly shorter in cirrhotic patients (vs non-cirrhotics and healthy subjects) (71.0 ± 11.3 s vs. 82.4 ± 15.6 s, 86.3 ± 20.3 s, P < 0.05). MTTs in the patients with liver cirrhosis were significantly shorter than those of controls (111.9 ± 22.0 s vs. 139.4 ± 39.8 s, P < 0.05), but there was no significant difference between the cirrhotic and non-cirrhotic groups (111.9 ± 22.0 s vs. 110.3 ± 14.6 s). Peak enhancement in the patients with liver cirrhosis was also higher than that observed in controls (23.9 ± 5.9 vs. 18.9 ± 7.1, P = 0.05). There were no significant intergroup differences in the RBVs and RBFs. Qontrast-assisted CEUS revealed reproducible differences in liver perfusion parameters during the development of hepatic fibrogenesis.

  16. [The implementation of the method of enhanced external counter pulsation for the treatment of cardiovascular diseases].

    Science.gov (United States)

    Badtieva, V A; Voroshilova, D N

    2018-05-21

    The cardiovascular diseases occupy a leading place in the structure of overall morbidity affecting the population not only of Russia but also of the majority of the developed countries throughout the world; they thus impose the heavy social and economic burden on both the public healthcare services and the modern society in general. At the same time, systemic atherosclerosis is considered to be one of the most common, severe, and life-threatening condition. Despite the presence of a large number of pharmaceutical and surgical methods for the treatment of this pathology, they are not infrequently lacking the desired effectiveness. The use of the shunting operations and endovascular methods failed to radically resolve the problem of managing systemic atherosclerosis and atherosclerosis of the lower limbs. A relatively novel approach which currently begins to find the ever increasing application for the treatment of patients presenting with cardiovascular pathology is based on the enhanced external counter-pulsation method although both the clinical and theoretical prerequisites of its application were developed rather long ago. This non-invasive therapeutic method allows to increase the perfusion pressure in the coronary arteries in diastole and to reduce the resistance to the cardiac ejection in the systole. The objective of this review article was to perform the analysis of the available literature publications on the use of the enhanced external counter-pulsation technique for the treatment of the patients presenting with the diseases of the cardiovascular system and to evaluate the clinical effectiveness of this approach as well as the availability of the treatment for the patients.

  17. Improved parenchymal liver enhancement with extended delay on Gd-EOB-DTPA-enhanced MRI in patients with parenchymal liver disease: associated clinical and imaging factors

    International Nuclear Information System (INIS)

    Esterson, Y.B.; Flusberg, M.; Oh, S.; Mazzariol, F.; Rozenblit, A.M.; Chernyak, V.

    2015-01-01

    Aim: To establish the effect of prolonged hepatobiliary phase (HBP) delay time on hepatic enhancement in patients with parenchymal liver disease (PLD). Materials and methods: Gadoxetate disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) examinations with HBP were obtained after 20- (HBP-20) and 30-minute (HBP-30) delays in patients with PLD. For each patient, the Model for End-Stage Liver Disease (MELD) score, total and direct bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), prothrombin time (PT), and partial thromboplastin time (PTT) were recorded. Signal intensities of the liver, main portal vein, and spleen on pre-contrast, HBP-20, and HBP-30 were documented. Signal intensities were used to calculate liver relative enhancement (LRE), liver–spleen index (LSI), and liver–portal vein index (LPI) for HBP-20 and HBP-30. Improved hepatic enhancement was considered if two or more indices were higher on HBP-30 than HBP-20. A logistic regression model was constructed with improved hepatic enhancement as the outcome. Results: One hundred and twenty-nine patients underwent 142 MRIs. Mean LRE, LSI, and LPI each increased from HBP-20 to HBP-30 (p = 0.004, p < 0.001, and p < 0.001, respectively). Seventy-two point five percent of cases demonstrated improved hepatic enhancement. The odds ratios for improved hepatic enhancement were 0.85 for MELD score (p = 0.02) and 3.2 for the 3 T scanner (p = 0.02), adjusted for age and sex. Conclusion: Increasing HBP delay to 30 minutes improves hepatic enhancement in patients with PLD, particularly if using a 3 T scanner. This effect is attenuated with higher MELD scores. -- Highlights: •Increasing hepatobiliary phase delay improves hepatic enhancement in liver disease. •This effect is enhanced if using a 3T scanner. •This effect is attenuated with higher MELD scores

  18. Graft-versus-host disease is enhanced by selective CD73 blockade in mice.

    Directory of Open Access Journals (Sweden)

    Long Wang

    Full Text Available CD73 functions as an ecto-5'-nucleotidase to produce extracellular adenosine that has anti-inflammatory and immunosuppressive activity. We here demonstrate that CD73 helps control graft-versus-host disease (GVHD in mouse models. Survival of wild-type (WT recipients of either allogeneic donor naïve CD73 knock-out (KO or WT T cells was similar suggesting that donor naïve T cell CD73 did not contribute to GVHD. By contrast, donor CD73 KO CD4(+CD25(+ regulatory T cells (Treg had significantly impaired ability to mitigate GVHD mortality compared to WT Treg, suggesting that CD73 on Treg is critical for GVHD protection. However, compared to donor CD73, recipient CD73 is more effective in limiting GVHD. Pharmacological blockade of A2A receptor exacerbated GVHD in WT recipients, but not in CD73 KO recipients, suggesting that A2 receptor signaling is primarily implicated in CD73-mediated GVHD protection. Moreover, pharmacological blockade of CD73 enzymatic activity induced stronger alloreactive T cell activity, worsened GVHD and enhanced the graft-versus-leukemia (GVL effect. These findings suggest that both donor and recipient CD73 protects against GVHD but also limits GVL effects. Thus, either enhancing or blocking CD73 activity has great potential clinical application in allogeneic bone marrow transplants.

  19. Genomic deletion of a long-range bone enhancer misregulatessclerostin in Van Buchem disease

    Energy Technology Data Exchange (ETDEWEB)

    Loots, Gabriela G.; Kneissel, Michaela; Keller, Hansjoerg; Baptist, Myma; Chang, Jessie; Collette, Nicole M.; Ovcharenko, Dmitriy; Plajzer-Frick, Ingrid; Rubin, Edward M.

    2005-04-15

    Mutations in distant regulatory elements can negatively impact human development and health, yet due to the difficulty of detecting these critical sequences we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem disease (VB), a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis we characterized the expression of human sclerostin (sost) from normal (hSOSTwt) or Van Buchem(hSOSTvb D) alleles. Only the hSOSTwt allele faithfully expressed high levels of human sost in the adult bone and impacted bone metabolism, consistent with the model that the VB noncoding deletion removes a sost specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays we were able to identify a candidate enhancer element that drives human sost expression in osteoblast-like cell lines in vitro and in the skeletal anlage of the E14.5 mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.

  20. Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models

    Science.gov (United States)

    Shin, Jin Young; Park, Hyun Jung; Kim, Ha Na; Oh, Se Hee; Bae, Jae-Sung; Ha, Hee-Jin; Lee, Phil Hyu

    2014-01-01

    Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment. PMID:24149893

  1. Contrast-enhanced Ultrasound for Detection of Crohn's Disease Activity: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Serafin, Zbigniew; Białecki, Marcin; Białecka, Agnieszka; Sconfienza, Luca Maria; Kłopocka, Maria

    2016-03-01

    Reports on imaging of active Crohn's disease (aCD) using contrast-enhanced ultrasound (CEUS) are encouraging. However, the statistical power of most published papers is limited due to the small size of the patient groups included. This study was performed to verify the diagnostic value of CEUS in detecting aCD. A systematic literature search was performed by two independent reviewers for articles on the test characteristics of CEUS for the identification of aCD. The quality of the analysed studies was evaluated using a quality assessment tool for diagnostic accuracy studies (QUADAS-2). Pooling was performed using a diagnostic random-effect model and bivariate analysis. Eight articles were included in the final analysis, with a total of 332 patients. There was no significant publication bias. Significant heterogeneity was found regarding CEUS methodology and sonographic definitions of aCD. In a bivariate analysis, pooled sensitivity was 0.94 (95% CI 0.87-0.97) and pooled specificity was 0.79 (95% CI 0.67-0.88). Spearman correlation statistics presented no significant diagnostic threshold effect (r = 0.12, p > 0.9). Subgroup analysis showed that relative intestine wall enhancement had the highest diagnostic value (area under the curve 94%), while the presence of enhancement and analysis of the slope were less useful (area under the curve 91 and 90%, respectively). CEUS presents good sensitivity and moderate specificity in the detection of the aCD. Large-scale randomized trials with quantitative evaluation of CEUS images are necessary to promote this technique in clinical practice. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Music-Based Memory Enhancement in Alzheimer’s Disease: Promise and Limitations

    Science.gov (United States)

    Simmons-Stern, Nicholas R.; Deason, Rebecca G.; Brandler, Brian J.; Frustace, Bruno S.; O’Connor, Maureen K.; Ally, Brandon A.; Budson, Andrew E.

    2012-01-01

    In a previous study (Simmons-Stern, Budson, & Ally 2010), we found that patients with Alzheimer’s disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD. PMID:23000133

  3. Music-based memory enhancement in Alzheimer's disease: promise and limitations.

    Science.gov (United States)

    Simmons-Stern, Nicholas R; Deason, Rebecca G; Brandler, Brian J; Frustace, Bruno S; O'Connor, Maureen K; Ally, Brandon A; Budson, Andrew E

    2012-12-01

    In a previous study (Simmons-Stern, Budson & Ally, 2010), we found that patients with Alzheimer's disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD. Published by Elsevier Ltd.

  4. An enhanced voxel-based morphometry method to investigate structural changes: application to Alzheimer's disease

    International Nuclear Information System (INIS)

    Li, Xingfeng; Messe, Arnaud; Marrelec, Guillaume; Pelegrini-Issac, Melanie; Benali, Habib

    2010-01-01

    When characterizing regional cerebral gray matter differences in structural magnetic resonance images (sMRI) by voxel-based morphometry (VBM), one faces a known drawback of VBM, namely that histogram unequalization in the intensity images introduces false-positive results. To overcome this limitation, we propose to improve VBM by a new approach (called eVBM for enhanced VBM) that takes the histogram distribution of the sMRI into account by adding a histogram equalization step within the VBM procedure. Combining this technique with two most widely used VBM software packages (FSL and SPM), we studied GM variability in a group of 62 patients with Alzheimer's disease compared to 73 age-matched elderly controls. The results show that eVBM can reduce the number of false-positive differences in gray matter concentration. Because it takes advantage of the properties of VBM while improving sMRI histogram distribution at the same time, the proposed method is a powerful approach for analyzing gray matter differences in sMRI and may be of value in the investigation of sMRI gray and white matter abnormalities in a variety of brain diseases. (orig.)

  5. Enhanced Chemokine Receptor Expression on Leukocytes of Patients with Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    David Goldeck

    Full Text Available Although primarily a neurological complaint, systemic inflammation is present in Alzheimer's Disease, with higher than normal levels of proinflammatory cytokines and chemokines in the periphery as well as the brain. A gradient of these factors may enhance recruitment of activated immune cells into the brain via chemotaxis. Here, we investigated the phenotypes of circulating immune cells in AD patients with multi-colour flow cytometry to determine whether their expression of chemokine receptors is consistent with this hypothesis. In this study, we confirmed our previously reported data on the shift of early- to late-differentiated CD4+ T-cells in AD patients. The percentage of cells expressing CD25, a marker of acute T-cell activation, was higher in patients than in age-matched controls, and percentages of CCR6+ cells were elevated. This chemokine receptor is primarily expressed on pro-inflammatory memory cells and Th17 cells. The proportion of cells expressing CCR4 (expressed on Th2 cells and CCR5 (Th1 cells and dendritic cells was also greater in patients, and was more pronounced on CD4+ than CD8+ T-cells. These findings allow a more detailed insight into the systemic immune status of patients with Alzheimer's disease and suggest possible novel targets for immune therapy.

  6. Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease

    Directory of Open Access Journals (Sweden)

    Cristen Chafin

    2010-10-01

    the lack of PPAR-γ expression enhances inflammatory renal disease in the anti-GBM antibody-induced glomerulonephritis mouse model and suggests targeting PPAR-γ may have therapeutic efficacy.Keywords: PPAR-γ, antiglomerular basement membrane disease 

  7. Carvedilol Enhances the Antioxidant Effect of Vitamins E and C in Chronic Chagas Heart Disease

    International Nuclear Information System (INIS)

    Budni, Patrícia; Pedrosa, Roberto Coury; Dalmarco, Eduardo Monguilhott; Dalmarco, Juliana Bastos; Frode, Tânia Sílvia; Wilhelm, Danilo Filho

    2013-01-01

    Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. The decrease in oxidative

  8. Carvedilol Enhances the Antioxidant Effect of Vitamins E and C in Chronic Chagas Heart Disease

    Energy Technology Data Exchange (ETDEWEB)

    Budni, Patrícia, E-mail: budnip@gmail.com [Universidade Federal de Santa Catarina, Florianópolis, SC (Brazil); Pedrosa, Roberto Coury [Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil); Dalmarco, Eduardo Monguilhott; Dalmarco, Juliana Bastos; Frode, Tânia Sílvia; Wilhelm, Danilo Filho [Universidade Federal de Santa Catarina, Florianópolis, SC (Brazil)

    2013-10-15

    Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. The decrease in oxidative

  9. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models.

    Directory of Open Access Journals (Sweden)

    Scott B Raymond

    Full Text Available Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP, across a large age range (9-26 months, with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.

  10. Contrast-enhanced magnetic resonance venography in pediatric patients with chronic kidney disease: initial experience with ferumoxytol

    International Nuclear Information System (INIS)

    Luhar, Aarti; Khan, Sarah; Ghahremani, Shahnaz; Griggs, Rachel; Hall, Theodore R.; Finn, J.P.; Zaritsky, Joshua; Salusky, Isidro

    2016-01-01

    Ferumoxytol is an ultra-small superparamagnetic iron oxide (USPIO) particle that is FDA-approved for parenteral treatment of iron deficiency anemia in adults with chronic kidney disease. Because of the association between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with severe chronic kidney disease, we sought to evaluate the diagnostic role of ferumoxytol-enhanced MR venography in children with chronic kidney disease. Twenty children underwent 22 high-resolution ferumoxytol-enhanced MR venography examinations at 3.0 T. High-resolution 3-D contrast-enhanced imaging was performed at a minimum of 3 time points following injection of ferumoxytol at a total dose of 4 mg/kg. Two blinded pediatric radiologists independently scored six named veins on ferumoxytol-enhanced MR venography examinations according to a three-point subjective score, where a score ≥2 was considered diagnostic. Additionally, all relevant venous structures in the included field of view were analyzed for occlusive or non-occlusive thrombosis, compression and presence of collaterals. All patients underwent ferumoxytol-enhanced MR venography successfully and without adverse event. The overall scores of the reviewing radiologists for all venous structures were 2.7-2.9. In all cases, the reviewers were confident basing their diagnoses on the ferumoxytol-enhanced MR venography findings. In 12 of 22 examinations, findings on follow-up imaging or invasive procedures were available to correlate with the findings on ferumoxytol-enhanced MR venography. There was complete concordance between the findings from follow-up imaging and invasive procedures with findings from ferumoxytol-enhanced MR venography. Ferumoxytol holds promise as a powerful alternative to gadolinium-based contrast agents for reliable, high-resolution MR venography in children with chronic kidney disease. (orig.)

  11. Atypical Distribution of Late Gadolinium Enhancement of the Left Ventricle on Cardiac Magnetic Resonance in Classical Anderson-Fabry Disease

    OpenAIRE

    Kasuya, Shusuke; Suzuki, Masayo; Inaoka, Tsutomu; Odashima, Masayuki; Nakatsuka, Tomoya; Ishikawa, Rumiko; Tokuyama, Wataru; Terada, Hitoshi

    2016-01-01

    Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A. Approximately 50% of patients with AFD may have cardiac involvement. Gadolinium-enhanced cardiac magnetic resonance (CMR) is useful for the diagnosis of cardiac involvement of AFD by recognizing typical late gadolinium enhancement (LGE) patterns. We report a 48-year-old man with cardiac involvement in classical AFD, showing atypical distribution of the LGE at the mid-lateral...

  12. Enhanced surveillance strategies for detecting and monitoring chronic wasting disease in free-ranging cervids

    Science.gov (United States)

    Walsh, Daniel P.

    2012-01-01

    The purpose of this document is to provide wildlife management agencies with the foundation upon which they can build scientifically rigorous and cost-effective surveillance and monitoring programs for chronic wasting disease (CWD) or refine their existing programs. The first chapter provides an overview of potential demographic and spatial risk factors of susceptible wildlife populations that may be exploited for CWD surveillance and monitoring. The information contained in this chapter explores historic as well as recent developments in our understanding of CWD disease dynamics. It also contains many literature references for readers who may desire a more thorough review of the topics or CWD in general. The second chapter examines methods for enhancing efforts to detect CWD on the landscape where it is not presently known to exist and focuses on the efficiency and cost-effectiveness of the surveillance program. Specifically, it describes the means of exploiting current knowledge of demographic and spatial risk factors, as described in the first chapter, through a two-stage surveillance scheme that utilizes traditional design-based sampling approaches and novel statistical methods to incorporate information about the attributes of the landscape, environment, populations and individual animals into CWD surveillance activities. By accounting for these attributes, efficiencies can be gained and cost-savings can be realized. The final chapter is unique in relation to the first two chapters. Its focus is on designing programs to monitor CWD once it is discovered within a jurisdiction. Unlike the prior chapters that are more detailed or prescriptive, this chapter by design is considerably more general because providing comprehensive direction for creating monitoring programs for jurisdictions without consideration of their monitoring goals, sociopolitical constraints, or their biological systems, is not possible. Therefore, the authors draw upon their collective

  13. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  14. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Larson JL

    2014-10-01

    Full Text Available Janet L Larson,1,2 Margaret K Covey,2 Mary C Kapella,2 Charles G Alex,3,4 Edward McAuley,5 1Division of Acute, Critical and Long-Term Care Programs, School of Nursing, University of Michigan, Ann Arbor, MI, 2Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, 3Division of Pulmonary and Critical Care Medicine, Edward Hines Jr VA Hospital, Hines, IL, 4Advocate Christ Medical Center, Oaklawn, IL, 5Department of Kinesiology and Community Health, College of Applied Health Sciences, University of Illinois Urbana-Champagne, Urbana, IL, USA Background: People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. Methods: In this randomized controlled trial, subjects were assigned to: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR, health education with upper body resistance training (ED-UBR, or health education with gentle chair exercises (ED-Chair. Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Results: Differences were observed in light physical activity (LPA after 4 months of training, time by group interaction effect (P=0.045. The SE-UBR group increased time spent in

  15. The clinical application of static-fluid MRU and enhanced MRU for the diagnosis of upper urinary tract disease

    International Nuclear Information System (INIS)

    Hu Bing; Ye Binbin; Kang Zhuang; Zou Yan

    2005-01-01

    Objective: To evaluate the clinical utility of heavy T 2 -weighted MR urography (static-fluid MRU) and gadolinium-enhanced T 1 -weighted MR urography (enhanced MRU) for the diagnosis of upper urinary tract disease. Methods: Eleven patients were examined with static-fluid MRU and enhanced MRU. The images of static-fluid MRU and enhanced MRU were ranked and diagnosed by two radiologists. And the results were compared later. Results: The ranked image quality was analyzed with a Wilcoxon sign-rank test. The difference between two kinds of MRU images was not significant (P>0.05). The number of correct diagnosis of static-fluid MRU was 19(86.4%) by observer A and 18 (81.8%) by observer B; of enhanced MRU was 21 (95.5%) by observer A and 19 (86.4%) by observer B. Conclusion: With static-fluid MRU, the intraluminal anatomy of urinary tract can be displayed, but the function of kidney can not be evaluated. With enhanced MRU, the intraluminal anatomy can be displayed, and the function of kidney can be evaluated as well. Most of upper urinary tract disease could be diagnosed by static-fluid MRU or enhanced MRU. (authors)

  16. Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease.

    Science.gov (United States)

    Schneider, Frank; Habel, Ute; Volkmann, Jens; Regel, Sabine; Kornischka, Jürgen; Sturm, Volker; Freund, Hans-Joachim

    2003-03-01

    High-frequency electrical stimulation of the subthalamic nucleus is a new and highly effective therapy for complications of long-term levodopa therapy and motor symptoms in advanced Parkinson disease (PD). Clinical observations indicate additional influence on emotional behavior. Electrical stimulation of deep brain nuclei with pulse rates above 100 Hz provokes a reversible, lesioning-like effect. Here, the effect of deep brain stimulation of the subthalamic nucleus on emotional, cognitive, and motor performance in patients with PD (n = 12) was examined. The results were compared with the effects of a suprathreshold dose of levodopa intended to transiently restore striatal dopamine deficiency. Patients were tested during medication off/stimulation off (STIM OFF), medication off/stimulation on (STIM ON), and during the best motor state after taking levodopa without deep brain stimulation (MED). More positive self-reported mood and an enhanced mood induction effect as well as improvement in emotional memory during STIM ON were observed, while during STIM OFF, patients revealed reduced emotional performance. Comparable effects were revealed by STIM ON and MED. Cognitive performance was not affected by the different conditions and treatments. Deep brain stimulation of the subthalamic nucleus selectively enhanced affective processing and subjective well-being and seemed to be antidepressive. Levodopa and deep brain stimulation had similar effects on emotion. This finding may provide new clues about the neurobiologic bases of emotion and mood disorders, and it illustrates the important role of the basal ganglia and the dopaminergic system in emotional processing in addition to the well-known motor and cognitive functions.

  17. Initial staging of Hodgkin's disease: role of contrast-enhanced 18F FDG PET/CT.

    Science.gov (United States)

    Chiaravalloti, Agostino; Danieli, Roberta; Caracciolo, Cristiana Ragano; Travascio, Laura; Cantonetti, Maria; Gallamini, Andrea; Guazzaroni, Manlio; Orlacchio, Antonio; Simonetti, Giovanni; Schillaci, Orazio

    2014-08-01

    The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin's disease (HD).Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard.No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor).Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients.

  18. Enhanced Disease Surveillance during the 2012 Republican National Convention, Tampa, FL

    Science.gov (United States)

    Atrubin, David; Wiese, Michael; Snider, Rebecca; Workman, Kiley; McDougle, Warren

    2013-01-01

    deployed in Tampa during the RNC. Data was collected electronically and transmitted through ESSENCE as well. The HCHD also asked infection preventionists, health care providers, hotels, labs, and Mosquito Control to lower their reporting threshold to us during the RNC period. We provided updates to all our partners with respect to diseases and outbreaks of public health importance occurring in our county. Results No epidemiologic events linked to the RNC were detected through the HCHD’s enhanced surveillance that was conducted. Decreased patient volumes were seen during the RNC at our EDs closest to the convention site. No significant increases in ED visits from outside of our 5-county area were noted during the RNC. Urgent care centers reported seeing patients associated with the RNC for a variety of reasons including respiratory and gastrointestinal illness. DMAT surveillance showed mainly routine visits but four secret service agents did seek care for respiratory illness during the convention. Conclusions Substantial time and resources were devoted to disease surveillance in the 6 months leading up to the RNC and during the event. While no epidemiologic events were detected, the public health surveillance infrastructure has clearly been strengthened in our county. We are receiving our ED syndromic data, from many of our hospitals, every two hours as opposed to every day. We have established relationships with our urgent case centers and hope to begin receiving urgent care center data on a daily basis in the near future. Receiving DMAT data through ESSENCE could prove very useful in the future, especially in Florida where hurricanes are always a threat. Lastly the improved relationships with our health care providers should be beneficial as we move forward.

  19. Genetic engineering to enhance crop-based phytonutrients (nutraceuticals) to alleviate diet-related diseases.

    Science.gov (United States)

    Mattoo, Autar K; Shukla, Vijaya; Fatima, Tahira; Handa, Avtar K; Yachha, Surender K

    2010-01-01

    Nutrition studies have provided unambiguous evidence that a number of human health maladies including chronic coronary artery, hypertension, diabetes, osteoporosis, cancer and age- and lifestyle-related diseases are associated with the diet. Several favorable and a few deleterious natural dietary ingredients have been identified that predispose human populations to various genetic and epigenetic based disorders. Media dissemination of this information has greatly raised public awareness of the beneficial effects due to increased consumption of fruit, vegetables and whole grain cereals-foods rich in phytonutrients, protein and fiber. However, the presence of intrinsically low levels of the beneficial phytonutrients in the available genotypes of crop plants is not always at par with the recommended daily allowance (RDA) for different phytonutrients (nutraceuticals). Molecular engineering of crop plants has offered a number of tools to markedly enhance intracellular concentrations of some of the beneficial nutrients, levels that, in some cases, are closer to the RDA threshold. This review brings together literature on various strategies utilized for bioengineering both major and minor crops to increase the levels of desirable phytonutrients while also decreasing the concentrations of deleterious metabolites. Some of these include increases in: protein level in potato; lysine in corn and rice; methionine in alfalfa; carotenoids (beta-carotene, phytoene, lycopene, zeaxanthin and lutein) in rice, potato, canola, tomato; choline in tomato; folates in rice, corn, tomato and lettuce; vitamin C in corn and lettuce; polyphenolics such as flavonol, isoflavone, resveratrol, chlorogenic acid and other flavonoids in tomato; anthocyanin levels in tomato and potato; alpha-tocopherol in soybean, oil seed, lettuce and potato; iron and zinc in transgenic rice. Also, molecular engineering has succeeded in considerably reducing the levels of the offending protein glutelin in rice

  20. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease.

    Science.gov (United States)

    Moon, James C; Sheppard, Mary; Reed, Emma; Lee, Phillip; Elliott, Perry M; Pennell, Dudley J

    2006-01-01

    Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress.

  1. The impact of aging and Alzheimer's disease on emotional enhancement of memory.

    Science.gov (United States)

    Baran, Zeynel; Cangöz, Banu; Ozel-Kizil, Erguvan T

    2014-01-01

    Emotional enhancement of memory (EEM) has been a well-known phenomenon which corresponds to the advantage of emotional stimuli to be better recalled than neutral ones. Previous studies suggest that aging favours recollection of positive items and this pattern is disrupted in Alzheimer's disease (AD). Emotional valence of different stimulus modalities, i.e. pictures and words, may also have an effect on each other's memory performances. However, none of these were clearly studied in AD. This study aimed to evaluate how emotional valences of simultaneously presented stimuli affected recall in healthy young (YG, n = 30), healthy elderly (HE, n = 30) participants and in patients with AD (n = 30). A battery consisting of emotional words presented on emotional pictures was developed. An analysis of a 3 (Groups) × 3 (Emotional Valence of Picture) × 3 (Emotional Valence of Word) mixed ANOVA design was carried out. Patients with AD could process emotional information similarly to healthy participants; however, they had EEM only for picture recalling. Emotional valence of the co-presented stimulus had a boosting effect both in the YG and HE, but not in AD group, especially if both of the stimuli had the same emotional valence. This study highlights the impaired EEM for verbal and preserved EEM for non-verbal declarative memory in patients with AD, the neurobiological underpinnings of which should be addressed by future studies. © 2014 S. Karger AG, Basel.

  2. Technology-enhanced practice for patients with chronic cardiac disease: home implementation and evaluation.

    Science.gov (United States)

    Brennan, Patricia Flatley; Casper, Gail R; Burke, Laura J; Johnson, Kathy A; Brown, Roger; Valdez, Rupa S; Sebern, Marge; Perez, Oscar A; Sturgeon, Billie

    2010-01-01

    This 3-year field experiment engaged 60 nurses and 282 patients in the design and evaluation of an innovative home-care nursing model, referred to as technology-enhanced practice (TEP). Nurses using TEP augmented the usual care with a web-based resource (HeartCareII) that provided patients with self-management information, self-monitoring tools, and messaging services. Patients exposed to TEP demonstrated better quality of life and self-management of chronic heart disease during the first 4 weeks, and were no more likely than patients in usual care to make unplanned visits to a clinician or hospital. Both groups demonstrated the same long-term symptom management and achievements in health status. This project provides new evidence that the purposeful creation of patient-tailored web resources within a hospital portal is possible; that nurses have difficulty with modifying their practice routines, even with a highly-tailored web resource; and that the benefits of this intervention are more discernable in the early postdischarge stages of care. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Arabidopsis EF-Tu receptor enhances bacterial disease resistance in transgenic wheat.

    Science.gov (United States)

    Schoonbeek, Henk-Jan; Wang, Hsi-Hua; Stefanato, Francesca L; Craze, Melanie; Bowden, Sarah; Wallington, Emma; Zipfel, Cyril; Ridout, Christopher J

    2015-04-01

    Perception of pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs) by pattern recognition receptors (PRRs) is a key component of plant innate immunity. The Arabidopsis PRR EF-Tu receptor (EFR) recognizes the bacterial PAMP elongation factor Tu (EF-Tu) and its derived peptide elf18. Previous work revealed that transgenic expression of AtEFR in Solanaceae confers elf18 responsiveness and broad-spectrum bacterial disease resistance. In this study, we developed a set of bioassays to study the activation of PAMP-triggered immunity (PTI) in wheat. We generated transgenic wheat (Triticum aestivum) plants expressing AtEFR driven by the constitutive rice actin promoter and tested their response to elf18. We show that transgenic expression of AtEFR in wheat confers recognition of elf18, as measured by the induction of immune marker genes and callose deposition. When challenged with the cereal bacterial pathogen Pseudomonas syringae pv. oryzae, transgenic EFR wheat lines had reduced lesion size and bacterial multiplication. These results demonstrate that AtEFR can be transferred successfully from dicot to monocot species, further revealing that immune signalling pathways are conserved across these distant phyla. As novel PRRs are identified, their transfer between plant families represents a useful strategy for enhancing resistance to pathogens in crops. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  4. Enhanced resistance to stripe rust disease in transgenic wheat expressing the rice chitinase gene RC24.

    Science.gov (United States)

    Huang, Xuan; Wang, Jian; Du, Zhen; Zhang, Chen; Li, Lan; Xu, Ziqin

    2013-10-01

    Stripe rust is a devastating fungal disease of wheat worldwide which is primarily caused by Puccinia striiformis f. sp tritici. Transgenic wheat (Triticum aestivum L.) expressing rice class chitinase gene RC24 were developed by particle bombardment of immature embryos and tested for resistance to Puccinia striiformis f.sp tritici. under greenhouse and field conditions. Putative transformants were selected on kanamycin-containing media. Polymease chain reaction indicated that RC24 was transferred into 17 transformants obtained from bombardment of 1,684 immature embryos. Integration of RC24 was confirmed by Southern blot with a RC24-labeled probe and expression of RC24 was verified by RT-PCR. Nine transgenic T1 lines exhibited enhanced resistance to stripe rust infection with lines XN8 and BF4 showing the highest level of resistance. Southern blot hybridization confirmed the stable inheritance of RC24 in transgenic T1 plants. Resistance to stripe rust in transgenic T2 and T3 XN8 and BF4 plants was confirmed over two consecutive years in the field. Increased yield (27-36 %) was recorded for transgenic T2 and T3 XN8 and BF4 plants compared to controls. These results suggest that rice class I chitinase RC24 can be used to engineer stripe rust resistance in wheat.

  5. Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus replication.

    Science.gov (United States)

    Meng, Chunchun; Zhou, Zhizhi; Jiang, Ke; Yu, Shengqing; Jia, Lijun; Wu, Yantao; Liu, Yanqing; Meng, Songshu; Ding, Chan

    2012-06-01

    Newcastle disease virus (NDV) can replicate in tumor cells and induce apoptosis in late stages of infection. However, the interaction between NDV and cells in early stages of infection is not well understood. Here, we report that, shortly after infection, NDV triggers the formation of autophagosomes in U251 glioma cells, as demonstrated by an increased number of double-membrane vesicles, GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) a dot formations, and elevated production of LC3II. Moreover, modulation of NDV-induced autophagy by rapamycin, chloroquine or small interfering RNAs targeting the genes critical for autophagosome formation (Atg5 and Beclin-1) affects virus production, indicating that autophagy may be utilized by NDV to facilitate its own production. Furthermore, the class III phosphatidylinositol 3-kinase (PI3K)/Beclin-1 pathway plays a role in NDV-induced autophagy and virus production. Collectively, our data provide a unique example of a paramyxovirus that uses autophagy to enhance its production.

  6. Extracellular matrix formation enhances the ability of Streptococcus pneumoniae to cause invasive disease.

    Directory of Open Access Journals (Sweden)

    Claudia Trappetti

    Full Text Available During infection, pneumococci exist mainly in sessile biofilms rather than in planktonic form, except during sepsis. However, relatively little is known about how biofilms contribute to pneumococcal pathogenesis. Here, we carried out a biofilm assay on opaque and transparent variants of a clinical serotype 19F strain WCH159. After 4 days incubation, scanning electron microscopy revealed that opaque biofilm bacteria produced an extracellular matrix, whereas the transparent variant did not. The opaque biofilm-derived bacteria translocated from the nasopharynx to the lungs and brain of mice, and showed 100-fold greater in vitro adherence to A549 cells than transparent bacteria. Microarray analysis of planktonic and sessile bacteria from transparent and opaque variants showed differential gene expression in two operons: the lic operon, which is involved in choline uptake, and in the two-component system, ciaRH. Mutants of these genes did not form an extracellular matrix, could not translocate from the nasopharynx to the lungs or the brain, and adhered poorly to A549 cells. We conclude that only the opaque phenotype is able to form extracellular matrix, and that the lic operon and ciaRH contribute to this process. We propose that during infection, extracellular matrix formation enhances the ability of pneumococci to cause invasive disease.

  7. Dopamine mediated iron release from ferritin is enhanced at higher temperatures: Possible implications for fever-induced Parkinson's disease

    International Nuclear Information System (INIS)

    Babincova, Melania; Babinec, Peter

    2005-01-01

    A new molecular mechanism is proposed to explain the pathogenesis of fever-induced Parkinson's disease. This proposal is based on dopamine and 6-hydroxydopamine-mediated free iron release from ferritin magnetic nanoparticles, which is enhanced at higher temperatures, and which may lead to substantial peroxidation and injury of lipid biomembranes of the substantia nigra in the brain

  8. Contrast-enhanced MR enterography as a stand-alone tool to evaluate Crohn's disease in a paediatric population

    International Nuclear Information System (INIS)

    Spieler, B.; Hindman, N.; Levy, J.; Zabrieski, K.; Sahlein, D.; Seuss, C.; Kim, S.

    2013-01-01

    Aim: To assess the performance of contrast-enhanced T1-weighted magnetic resonance imaging (MRI) alone in the evaluation of Crohn's disease in comparison to all magnetic resonance enterography (MRE) imaging sequences together in an attempt to suggest limitation of the number of overall unenhanced sequences need for the follow-up evaluation. Materials and methods: Twenty-five paediatric patients (mean age 14.1 ± 3.7 years, male = 12, female = 13) underwent MRE at 1.5 T for evaluation of Crohn's disease. Two radiologists reviewed only contrast-enhanced T1-weighted images in consensus on the first session. Whole images including unenhanced (steady-state free precession, single-shot fast spin-echo (HASTE), fat-suppressed T2-weighted) and contrast-enhanced T1-weighted sequences were reviewed in consensus during the second session with a 1 month interval, which was used as a reference standard. The readers evaluated the presence or absence of disease in 10 bowel segments in each patient. For the abnormal bowel segments, the readers then evaluated for active versus inactive disease and for the presence or absence of abscess. Sensitivity, specificity, and overall accuracy were calculated for detecting active inflammation. Results: There were 53/250 bowel segments with active inflammation using the reference standard imaging method. The sensitivity, specificity, and accuracy for diagnosing active inflammation using contrast-enhanced images alone were 83.3%, 86.9%, and 84.9%. In five of the false-positive cases of detecting abscess from contrast-enhanced imaging alone, absence of abscesses was confirmed on the non-fat-suppressed HASTE images. Conclusion: The number of MRE sequences in paediatric Crohn's patients can be decreased while maintaining diagnostic accuracy using contrast-enhanced T1 and non-fat-suppressed HASTE images

  9. Enhanced Dupuytren's disease fibroblast populated collagen lattice contraction is independent of endogenous active TGF-β2

    Directory of Open Access Journals (Sweden)

    Howard Jeffrey

    2004-11-01

    Full Text Available Abstract Background Dupuytren's disease (DD is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords leading to flexion contractures of the fingers and loss of hand function. Although the molecular mechanism of DD is unknown, it has been suggested that transforming growth factor-β2 (TGF-β2 may play an important role in the underlying patho-physiology of the disease. The purpose of this study was to further explore this hypothesis by examining the effects of TGF-β2 on primary cell cultures derived from patient-matched disease and normal palmar fascia tissue using a three-dimensional collagen contraction assay. Methods Fibroblast-populated collagen lattice (FPCL contraction assays using primary cell cultures derived from diseased and control fascia of the same DD patients were studied in response to exogenous TGF-β2 and neutralizing anti-TGF-β2 antibodies. Results Contraction of the FPCLs occurred significantly faster and to a greater extent in disease cells compared to control cells. The addition of TGF-β2 enhanced the rate and degree of collagen contraction in a dose-dependent fashion for both control and diseased cells. Neutralizing anti-TGF-β2 antibodies abolished exogenous TGF-β2 stimulated collagen contraction, but did not inhibit the enhanced basal collagen contraction activity of disease FPCL cultures. Conclusions Although exogenous TGF-β2 stimulated both disease and control FPCL contraction, neutralizing anti-TGF-β2 antibodies did not affect the elevated basal collagen contraction activity of disease FPCLs, suggesting that the differences in the collagen contraction activity of control and disease FPCL cultures are not due to differences in the levels of endogenous TGF-β2 activity.

  10. Assessment of arterial wall enhancement for differentiation of parent artery disease from small artery disease: Comparison between histogram analysis and visual analysis on 3 dimensional contrast-enhanced T1-weighted turbo spin echo MR images at 3T

    International Nuclear Information System (INIS)

    Jang, Jin Hee; Kim, Tae Won; Hwang, Eo Jin; Choi, Hyun Seok; Koo, Ja Seung; Shin, Yong Sam; Jung, So Lyung; Ahn, Kook Jin; Kim, Bum Soo

    2017-01-01

    The purpose of this study was to compare the histogram analysis and visual scores in 3T MRI assessment of middle cerebral arterial wall enhancement in patients with acute stroke, for the differentiation of parent artery disease (PAD) from small artery disease (SAD). Among the 82 consecutive patients in a tertiary hospital for one year, 25 patients with acute infarcts in middle cerebral artery (MCA) territory were included in this study including 15 patients with PAD and 10 patients with SAD. Three-dimensional contrast-enhanced T1-weighted turbo spin echo MR images with black-blood preparation at 3T were analyzed both qualitatively and quantitatively. The degree of MCA stenosis, and visual and histogram assessments on MCA wall enhancement were evaluated. A statistical analysis was performed to compare diagnostic accuracy between qualitative and quantitative metrics. The degree of stenosis, visual enhancement score, geometric mean (GM), and the 90th percentile (90P) value from the histogram analysis were significantly higher in PAD than in SAD (p = 0.006 for stenosis, < 0.001 for others). The receiver operating characteristic curve area of GM and 90P were 1 (95% confidence interval [CI], 0.86-1.00). A histogram analysis of a relevant arterial wall enhancement allows differentiation between PAD and SAD in patients with acute stroke within the MCA territory

  11. Assessment of arterial wall enhancement for differentiation of parent artery disease from small artery disease: Comparison between histogram analysis and visual analysis on 3 dimensional contrast-enhanced T1-weighted turbo spin echo MR images at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jin Hee; Kim, Tae Won; Hwang, Eo Jin; Choi, Hyun Seok; Koo, Ja Seung; Shin, Yong Sam; Jung, So Lyung; Ahn, Kook Jin; Kim, Bum Soo [College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2017-04-15

    The purpose of this study was to compare the histogram analysis and visual scores in 3T MRI assessment of middle cerebral arterial wall enhancement in patients with acute stroke, for the differentiation of parent artery disease (PAD) from small artery disease (SAD). Among the 82 consecutive patients in a tertiary hospital for one year, 25 patients with acute infarcts in middle cerebral artery (MCA) territory were included in this study including 15 patients with PAD and 10 patients with SAD. Three-dimensional contrast-enhanced T1-weighted turbo spin echo MR images with black-blood preparation at 3T were analyzed both qualitatively and quantitatively. The degree of MCA stenosis, and visual and histogram assessments on MCA wall enhancement were evaluated. A statistical analysis was performed to compare diagnostic accuracy between qualitative and quantitative metrics. The degree of stenosis, visual enhancement score, geometric mean (GM), and the 90th percentile (90P) value from the histogram analysis were significantly higher in PAD than in SAD (p = 0.006 for stenosis, < 0.001 for others). The receiver operating characteristic curve area of GM and 90P were 1 (95% confidence interval [CI], 0.86-1.00). A histogram analysis of a relevant arterial wall enhancement allows differentiation between PAD and SAD in patients with acute stroke within the MCA territory.

  12. Clinical use of gadobutrol for contrast-enhanced magnetic resonance imaging of neurological diseases

    Directory of Open Access Journals (Sweden)

    Cheng KT

    2012-02-01

    Full Text Available Kenneth T Cheng1, Hannah Y Cheng2, Kam Leung31Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA; 2Freelance Technical Writer, New Orleans, LA, USA; 3National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USAAbstract: Contrast-enhanced magnetic resonance imaging (CE-MRI is an important clinical tool for diagnosing neurological diseases. The appropriate use of a suitable MRI contrast agent or contrast pharmaceutical is essential for CE-MRI to produce desirable diagnostic images. Currently, there are seven contrast agents (CAs or pharmaceuticals approved for clinical imaging of the central nervous system (CNS in the US, Europe, or Japan. All of the clinically approved CAs are water-soluble gadolinium-based contrast agents (GBCAs which do not penetrate the CNS blood–brain barrier (BBB. These agents are used for imaging CNS areas without a BBB, or various pathologies, such as tumors and infection that break down the BBB and allow CAs to enter into the surrounding parenchyma. Clinically, GBCAs are most useful for detecting primary and secondary cerebral neoplastic lesions. Among these CNS GBCAs, gadobutrol (Gd-BT-DO3A, Gadovist™ is a neutral, nonionic, macrocyclic compound that showed promising results from clinical trials of CNS imaging. In comparison with other GBCAs, Gd-BT-DO3A has relatively high in vitro kinetic stability and r1 relaxivity. Gd-BT-DO3A has been recently approved by the US Food and Drug Administration (FDA in 2011 for CNS imaging. A review of available literature shows that Gd-BT-DO3A exhibits similar safety and clinical efficacy profiles to other GBCAs. Gd-BT-DO3A has the distinguishing feature that it is the only clinical agent commercially available in a formulation of 1.0 M concentration with a relatively higher in vitro T1 shortening per unit volume than other clinical GBCAs which are only

  13. Improved mitochondrial function in brain aging and Alzheimer disease - the new mechanism of action of the old metabolic enhancer piracetam

    Directory of Open Access Journals (Sweden)

    Kristina Leuner

    2010-09-01

    Full Text Available Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g. might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential (MMP, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease (AD. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, these new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions.

  14. Differential and enhanced response to climate forcing in diarrheal disease due to rotavirus across a megacity of the developing world.

    Science.gov (United States)

    Martinez, Pamela P; King, Aaron A; Yunus, Mohammad; Faruque, A S G; Pascual, Mercedes

    2016-04-12

    The role of climate forcing in the population dynamics of infectious diseases has typically been revealed via retrospective analyses of incidence records aggregated across space and, in particular, over whole cities. Here, we focus on the transmission dynamics of rotavirus, the main diarrheal disease in infants and young children, within the megacity of Dhaka, Bangladesh. We identify two zones, the densely urbanized core and the more rural periphery, that respond differentially to flooding. Moreover, disease seasonality differs substantially between these regions, spanning variation comparable to the variation from tropical to temperate regions. By combining process-based models with an extensive disease surveillance record, we show that the response to climate forcing is mainly seasonal in the core, where a more endemic transmission resulting from an asymptomatic reservoir facilitates the response to the monsoons. The force of infection in this monsoon peak can be an order of magnitude larger than the force of infection in the more epidemic periphery, which exhibits little or no postmonsoon outbreak in a pattern typical of nearby rural areas. A typically smaller peak during the monsoon season nevertheless shows sensitivity to interannual variability in flooding. High human density in the core is one explanation for enhanced transmission during troughs and an associated seasonal monsoon response in this diarrheal disease, which unlike cholera, has not been widely viewed as climate-sensitive. Spatial demographic, socioeconomic, and environmental heterogeneity can create reservoirs of infection and enhance the sensitivity of disease systems to climate forcing, especially in the populated cities of the developing world.

  15. Diagnostic Utility of Contrast-enhanced 3D T1-weighted Imaging in Acute Cerebral Infarction Associated with Graves Disease.

    Science.gov (United States)

    Gon, Yasufumi; Sakaguchi, Manabu; Oyama, Naoki; Mochizuki, Hideki

    2017-02-01

    Graves disease is rarely complicated with cerebrovascular steno-occlusive diseases. Previous studies have suggested several hypotheses for this occurrence, including excess thyroid hormone, which stimulates the sympathetic nervous system, which in turn causes an abnormal hemodynamic response with consequent atherosclerotic changes, and antithyroid antibodies cause local vascular inflammation in patients with Graves disease. However, radiological findings of vasculitis in patients with Graves disease and cerebral infarction remain less known. We report the case of a 30-year-old Japanese woman with acute cerebral infarction due to vasculitis associated with Graves disease. She was admitted to our hospital with a 4-day history of intermittent transient dysarthria and limb shaking of the left leg when standing. Three weeks before admission, she went to a local hospital because of general malaise and was diagnosed with Graves disease. Neurological examination revealed paralytic dysarthria, left central facial nerve palsy, and left hemiparesis (manual muscle testing, 4 of 5). Blood examinations showed hyperthyroidism (thyroid-stimulating hormone ≤.010 µU/mL; free T3 ≥25.0 pg/mL; free T4 ≥8.0 ng/dL) and elevation of antithyroid antibody levels (thyroid peroxidase antibody, 87 IU/mL). The vessel wall of the right internal carotid artery was markedly enhanced on contrast-enhanced three-dimensional T1-weighted magnetic resonance imaging, suggesting vasculitis. Magnetic resonance angiography revealed right internal carotid artery occlusion after the branching ophthalmic artery. Arterial stenosis due to vasculitis was considered the cause of hemodynamic ischemic stroke. Vessel wall imaging such as high-resolution contrast-enhanced T1-weighted imaging seems useful for assessing the underlying mechanism of stroke in patients with Graves disease. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Polyethylene glycol and contrast-enhanced MRI of Crohn's disease in children: preliminary experience.

    Science.gov (United States)

    Magnano, Gianmichele; Granata, Claudio; Barabino, Arrigo; Magnaguagno, Francesca; Rossi, Umberto; Calevo, Maria Grazia; Toma, Paolo

    2003-06-01

    To assess the ability of MRI to detect bowel abnormalities in children affected by Crohn's disease (CD). We studied 22 children (age range 8-18 years) referred to us with a known history of CD. MRI was carried out using a 1.5-T unit with a maximum gradient field strength of 16 mT and a phased-array body coil. The sequences performed were breath-hold coronal and axial T2-weighted, express fat saturation, followed by T1-weighted, spoiled gradient, fast fat saturation after IV injection of gadolinium chelate (0.3 mmol/kg) for contrast enhancement of the bowel wall. Bowel distension was achieved using oral administration of isosmotic polyethylene glycol solution. Ileo-colonoscopy was considered the gold standard for evaluation of superficial abnormalities and stenoses of the colon and terminal ileum. MRI findings of bowel-wall thickening, increased vascularisation and extramural involvement were compared with the findings using B-mode and Doppler US. Concordance between MRI and endoscopy, B-mode US and Doppler US findings was determined by the Kappa statistical method. Superficial lesions were not shown by MRI. MR enteroclysis easily detected stenoses, thickening and hyperaemia of bowel wall. Concordance of findings between MRI and endoscopy was 90% (K=0.79, substantial concordance). Concordance of findings between MRI and US concerning bowel-wall thickening and increased vascularisation was 95% (K=0.875, excellent concordance) and 80% (K=0.6, fairly good concordance), respectively. Our initial results show that MRI can detect intra- and extra-mural lesions of CD. The high concordance observed between MRI, endoscopy, US and Doppler US findings suggests that MRI is at least comparable for diagnostic capability with these techniques offering, thanks to multiplanar projections, an improved visualisation of the bowel without ionising radiation.

  17. Polyethylene glycol and contrast-enhanced MRI of Crohn's disease in children: preliminary experience

    International Nuclear Information System (INIS)

    Magnano, Gianmichele; Granata, Claudio; Magnaguagno, Francesca; Rossi, Umberto; Toma, Paolo; Barabino, Arrigo; Calevo, Maria Grazia

    2003-01-01

    To assess the ability of MRI to detect bowel abnormalities in children affected by Crohn's disease (CD). We studied 22 children (age range 8-18 years) referred to us with a known history of CD. MRI was carried out using a 1.5-T unit with a maximum gradient field strength of 16 mT and a phased-array body coil. The sequences performed were breath-hold coronal and axial T2-weighted, express fat saturation, followed by T1-weighted, spoiled gradient, fast fat saturation after IV injection of gadolinium chelate (0.3 mmol/kg) for contrast enhancement of the bowel wall. Bowel distension was achieved using oral administration of isosmotic polyethylene glycol solution. Ileo-colonoscopy was considered the gold standard for evaluation of superficial abnormalities and stenoses of the colon and terminal ileum. MRI findings of bowel-wall thickening, increased vascularisation and extramural involvement were compared with the findings using B-mode and Doppler US. Concordance between MRI and endoscopy, B-mode US and Doppler US findings was determined by the Kappa statistical method. Superficial lesions were not shown by MRI. MR enteroclysis easily detected stenoses, thickening and hyperaemia of bowel wall. Concordance of findings between MRI and endoscopy was 90% (K=0.79, substantial concordance). Concordance of findings between MRI and US concerning bowel-wall thickening and increased vascularisation was 95% (K=0.875, excellent concordance) and 80% (K=0.6, fairly good concordance), respectively. Our initial results show that MRI can detect intra- and extra-mural lesions of CD. The high concordance observed between MRI, endoscopy, US and Doppler US findings suggests that MRI is at least comparable for diagnostic capability with these techniques offering, thanks to multiplanar projections, an improved visualisation of the bowel without ionising radiation. (orig.)

  18. Coffee enhances the expression of chaperones and antioxidant proteins in rats with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Salomone, Federico; Li Volti, Giovanni; Vitaglione, Paola; Morisco, Filomena; Fogliano, Vincenzo; Zappalà, Agata; Palmigiano, Angelo; Garozzo, Domenico; Caporaso, Nicola; D'Argenio, Giuseppe; Galvano, Fabio

    2014-06-01

    Coffee consumption is inversely related to the degree of liver injury in patients with nonalcoholic fatty liver disease (NAFLD). Molecular mediators contributing to coffee's beneficial effects in NAFLD remain to be elucidated. In this study, we administrated decaffeinated espresso coffee or vehicle to rats fed an high-fat diet (HFD) for 12 weeks and examined the effects of coffee on liver injury by using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) proteomic analysis combined with mass spectrometry. Rats fed an HFD and water developed panacinar steatosis, lobular inflammation, and mild fibrosis, whereas rats fed an HFD and coffee exhibited only mild steatosis. Coffee consumption increased liver expression of the endoplasmic reticulum chaperones glucose-related protein 78 and protein disulfide-isomerase A3; similarly, coffee drinking enhanced the expression of the mitochondrial chaperones heat stress protein 70 and DJ-1. Furthermore, in agreement with reduced hepatic levels of 8-isoprostanes and 8-hydroxy-2'-deoxyguanosine, proteomic analysis showed that coffee consumption induces the expression of master regulators of redox status (i.e., peroxiredoxin 1, glutathione S-transferase α2, and D-dopachrome tautomerase). Last, proteomics revealed an association of coffee intake with decreased expression of electron transfer flavoprotein subunit α, a component of the mitochondrial respiratory chain, involved in de novo lipogenesis. In this study, we were able to identify by proteomic analysis the stress proteins mediating the antioxidant effects of coffee; moreover, we establish for the first time the contribution of specific coffee-induced endoplasmic reticulum and mitochondrial chaperones ensuring correct protein folding and degradation in the liver. Copyright © 2014 Mosby, Inc. All rights reserved.

  19. Vessel Wall Inflammation of Takayasu Arteritis Detected by Contrast-Enhanced Magnetic Resonance Imaging: Association with Disease Distribution and Activity.

    Directory of Open Access Journals (Sweden)

    Yoko Kato

    Full Text Available The assessment of the distribution and activity of vessel wall inflammation is clinically important in patients with Takayasu arteritis. Magnetic resonance imaging (MRI is a useful tool, but the clinical utility of late gadolinium enhancement (LGE in Takayasu arteritis has yet to be determined. The aim of the present study was to evaluate the utility of LGE in assessing vessel wall inflammation and disease activity in Takayasu arteritis.We enrolled 49 patients with Takayasu arteritis who had undergone 1.5 T MRI. Patients were divided into Active (n = 19 and Inactive disease (n = 30 groups. The distribution of vessel wall inflammation using angiography and LGE was assessed by qualitative analysis. In 79% and 63% of patients in Active and Inactive groups, respectively, greater distribution of vessel wall inflammation was observed with LGE than with conventional angiography. MRI values of pre- and post-contrast signal-to-noise ratios (SNR, SNR increment (post-SNR minus pre-SNR, pre- and post-contrast contrast-to-noise ratios (CNR, and CNR increment (post-CNR minus pre-CNR were evaluated at arterial wall sites with the highest signal intensity using quantitative analysis of post-contrast LGE images. No statistically significant differences in MRI parameters were observed between Active and Inactive groups. Contrast-enhanced MRI was unable to accurately detect active disease.Contrast-enhanced MRI has utility in detecting the distribution of vessel wall inflammation but has less utility in assessing disease activity in Takayasu arteritis.

  20. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

    Science.gov (United States)

    Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

    2013-08-28

    Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

  1. Value of gadoxetic acid-enhanced and diffusion-weighted MR imaging in evaluation of hepatocellular carcinomas with atypical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease

    International Nuclear Information System (INIS)

    Kim, Hyun Su; Kim, Seong Hyun; Kang, Tae Wook; Song, Kyoung Doo; Choi, Dongil; Park, Cheol Keun

    2015-01-01

    Highlights: •We investigated imaging findings on gadoxetic acid-enhanced MRI of HCCs without the typical enhancement pattern on multiphasic MDCT. •Most HCCs showed ancillary MR findings of typical HCC. •Considerable number of HCCs showed MR enhancement pattern of typical HCC. -- Abstract: Objective: The purpose of this study was to investigate the value of enhancement kinetics and ancillary imaging findings on gadoxetic acid-enhanced and diffusion-weighted (DW) MR imaging for diagnosing hepatocellular carcinomas (HCCs) without the typical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease. Materials and methods: Eighty-two surgically confirmed HCCs without the typical enhancement pattern (hypervascular in the arterial phase, followed by washout on the portal or equilibrium phases) on triple-phase MDCT were enrolled in this study. The patients were classified into four categories based on the CT density pattern of arterial and equilibrium phases (isodense–isodense, hypodense–hypodense, isodense–hypodense, and hyperdense–isodense) compared to liver parenchyma. Signal intensity of HCCs on T2-weighted images (T2WI), arterial phase, 3 min late-phase, hepatobiliary phase (HBP) and DW images with a b value of 800 s/mm 2 were qualitatively evaluated, and ADC values were measured. Fisher's exact test and Chi-square test were used to compare the frequency and trend of hyperintensity on T2WI, hypointensity on HBP images, hyperintensity on DW images, and histopathologic grades between groups with different CT density patterns. Kruskal–Wallis test was used to compare the ADC value between groups. Results: Thirty and 52 HCCs were categorized as hypervascular (hyperdense–isodense) and non-hypervascular HCCs (3, isodense–isodense; 37, hypodense–hypodense; 12, isodense–hypodense), respectively. Most HCCs showed hyperintensity on T2WI (77/82, 93.9%) and DW images (81/82, 98.8%) and hypointensity on HBP images

  2. Value of gadoxetic acid-enhanced and diffusion-weighted MR imaging in evaluation of hepatocellular carcinomas with atypical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Su [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul (Korea, Republic of); Kim, Seong Hyun, E-mail: kshyun@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul (Korea, Republic of); Kang, Tae Wook; Song, Kyoung Doo; Choi, Dongil [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul (Korea, Republic of); Park, Cheol Keun [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

    2015-04-15

    Highlights: •We investigated imaging findings on gadoxetic acid-enhanced MRI of HCCs without the typical enhancement pattern on multiphasic MDCT. •Most HCCs showed ancillary MR findings of typical HCC. •Considerable number of HCCs showed MR enhancement pattern of typical HCC. -- Abstract: Objective: The purpose of this study was to investigate the value of enhancement kinetics and ancillary imaging findings on gadoxetic acid-enhanced and diffusion-weighted (DW) MR imaging for diagnosing hepatocellular carcinomas (HCCs) without the typical enhancement pattern on contrast-enhanced multiphasic MDCT in patients with chronic liver disease. Materials and methods: Eighty-two surgically confirmed HCCs without the typical enhancement pattern (hypervascular in the arterial phase, followed by washout on the portal or equilibrium phases) on triple-phase MDCT were enrolled in this study. The patients were classified into four categories based on the CT density pattern of arterial and equilibrium phases (isodense–isodense, hypodense–hypodense, isodense–hypodense, and hyperdense–isodense) compared to liver parenchyma. Signal intensity of HCCs on T2-weighted images (T2WI), arterial phase, 3 min late-phase, hepatobiliary phase (HBP) and DW images with a b value of 800 s/mm{sup 2} were qualitatively evaluated, and ADC values were measured. Fisher's exact test and Chi-square test were used to compare the frequency and trend of hyperintensity on T2WI, hypointensity on HBP images, hyperintensity on DW images, and histopathologic grades between groups with different CT density patterns. Kruskal–Wallis test was used to compare the ADC value between groups. Results: Thirty and 52 HCCs were categorized as hypervascular (hyperdense–isodense) and non-hypervascular HCCs (3, isodense–isodense; 37, hypodense–hypodense; 12, isodense–hypodense), respectively. Most HCCs showed hyperintensity on T2WI (77/82, 93.9%) and DW images (81/82, 98.8%) and hypointensity on HBP

  3. Contrast-enhanced flair imaging in the evaluation of infectious leptomeningeal diseases

    International Nuclear Information System (INIS)

    Parmar, Hemant; Sitoh, Y.-Y.; Anand, Pooja; Chua, Violet; Hui, Francis

    2006-01-01

    Purpose: The purpose of our study was to compare contrast-enhanced fluid-attenuated inversion recovery (FLAIR) images with contrast-enhanced T1 weighted images for infectious leptomeningitis. Materials and methods: We studied twenty-four patients with a clinical suspicion of infectious meningitis with unenhanced FLAIR, contrast-enhanced T1 weighted and contrast-enhanced FLAIR MR sequences. Twelve patients had cytologic and biochemical diagnosis of meningitis on cerebrospinal fluid (CSF) examination obtained 48 h before or after the MR study. Sequences were considered positive if abnormal signal was seen in the subarachnoid space (cistern or sulci) or along pial surface. Results: Twenty-seven examinations in 24 patients were performed. Of the 12 patients (thirteen studies) in whom cytology was positive, unenhanced FLAIR images were positive in six cases (sensitivity 46%), contrast-enhanced FLAIR images were positive in 11 (sensitivity 85%), and contrast-enhanced T1 weighted MR images were positive in 11 patients (sensitivity 85%). Of the 12 patients (14 studies) in whom cerebrospinal fluid study was negative, unenhanced FLAIR images were negative in 13, contrast-enhanced FLAIR images were negative in 11, and contrast-enhanced T1 weighted MR images were negative in eight. Thus, the specificity of unenhanced FLAIR, contrast-enhanced FLAIR and contrast-enhanced T1 weighted images was 93, 79 and 57%, respectively. Conclusion: Our results suggest that post-contrast FLAIR images have similar sensitivity but a higher specificity compared to contrast-enhanced T1 weighted images for detection of leptomeningeal enhancement. It can be a useful adjunct to post-contrast T1 weighted images in evaluation of infectious leptomeningitis

  4. Contrast-enhanced flair imaging in the evaluation of infectious leptomeningeal diseases

    Energy Technology Data Exchange (ETDEWEB)

    Parmar, Hemant [Department of Neuroradiology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433 (Singapore) and Department of Diagnostic Imaging, Hospital for Sick Children, Toronto (Canada)]. E-mail: parurad@hotmail.com; Sitoh, Y.-Y. [Department of Neuroradiology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433 (Singapore); Anand, Pooja [Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng (Singapore); Chua, Violet [Department of Neuroradiology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433 (Singapore); Hui, Francis [Department of Neuroradiology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433 (Singapore)

    2006-04-15

    Purpose: The purpose of our study was to compare contrast-enhanced fluid-attenuated inversion recovery (FLAIR) images with contrast-enhanced T1 weighted images for infectious leptomeningitis. Materials and methods: We studied twenty-four patients with a clinical suspicion of infectious meningitis with unenhanced FLAIR, contrast-enhanced T1 weighted and contrast-enhanced FLAIR MR sequences. Twelve patients had cytologic and biochemical diagnosis of meningitis on cerebrospinal fluid (CSF) examination obtained 48 h before or after the MR study. Sequences were considered positive if abnormal signal was seen in the subarachnoid space (cistern or sulci) or along pial surface. Results: Twenty-seven examinations in 24 patients were performed. Of the 12 patients (thirteen studies) in whom cytology was positive, unenhanced FLAIR images were positive in six cases (sensitivity 46%), contrast-enhanced FLAIR images were positive in 11 (sensitivity 85%), and contrast-enhanced T1 weighted MR images were positive in 11 patients (sensitivity 85%). Of the 12 patients (14 studies) in whom cerebrospinal fluid study was negative, unenhanced FLAIR images were negative in 13, contrast-enhanced FLAIR images were negative in 11, and contrast-enhanced T1 weighted MR images were negative in eight. Thus, the specificity of unenhanced FLAIR, contrast-enhanced FLAIR and contrast-enhanced T1 weighted images was 93, 79 and 57%, respectively. Conclusion: Our results suggest that post-contrast FLAIR images have similar sensitivity but a higher specificity compared to contrast-enhanced T1 weighted images for detection of leptomeningeal enhancement. It can be a useful adjunct to post-contrast T1 weighted images in evaluation of infectious leptomeningitis.

  5. Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.

    Directory of Open Access Journals (Sweden)

    Julia María Martínez Gómez

    2016-03-01

    Full Text Available Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN receptors-deficient mice (AG129 born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of

  6. Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease

    International Nuclear Information System (INIS)

    Takamatsu, J.; Hosoya, T.; Naito, N.

    1988-01-01

    Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients. From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients. Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients. Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients

  7. The Impact of Gd-Eob-Dtpa-Enhanced MR Cholangiography in Biliary Diseases: Comparison with T2-Weighted MR Cholangiopancreatography

    Directory of Open Access Journals (Sweden)

    Evrim Özmen

    2016-06-01

    Full Text Available Background: Contrast enhanced magnetic resonance cholangiography is a novel technique and promising method in demonstrating biliary tree anatomy and evaluating biliary disorders. However, to date, there are a limited number of studies that have focused on the impact of this technique. Aims: We aimed to evaluate the additional role of contrast enhanced MR cholangiography (MRC and compare contrast enhanced MRC with T2-weighted (w magnetic resonance cholangiopancreatography (MRCP in the diagnosis of biliary disorders. Study Design: Diagnostic accuracy study. Methods: The T2w-MRCP and contrast enhanced MRC sequences of 31 patients whose gold standard test results were available were scored visually for the existence of pathological findings with regard to any of the biliary diseases. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA was used as the contrast agent. The correlation values were determined according to the statistical analysis made from those scores and the sensitivity, specificity and accuracy values of each sequence were detected as well. Results: We detected that the correlation values with gold standard methods of contrast enhanced MRC sequences were significantly higher than the ones of T2w-MRCP sequences. The correlation ratios of T2w-MRCP sequences were between 26 and 34%, while those for contrast enhanced MRC sequences were between 81 and 83% for the first reader and the correlation ratios of T2w-MRCP sequences were between 10 and 61%, whereas those of contrast enhanced MRC were between 79 and 81% for the second reader The mean sensitivity, specificity and accuracy values of T2w-MRCP sequences were 14.3-42.5%, 85-89.2% and 59.3-72.5%, respectively, while the mean sensitivity, specificity and accuracy values of contrast enhanced MRC sequences were 100%, 86.7% and 93.2-93.3%, respectively. Conclusion: We suggest that obtaining of contrast enhanced MRC sequences in addition to the T2w-MRCP can be useful in

  8. Mutation in Rice Abscisic Acid2 Results in Cell Death, Enhanced Disease-Resistance, Altered Seed Dormancy and Development

    Directory of Open Access Journals (Sweden)

    Yongxiang Liao

    2018-03-01

    Full Text Available Lesion mimic mutants display spontaneous cell death, and thus are valuable for understanding the molecular mechanism of cell death and disease resistance. Although a lot of such mutants have been characterized in rice, the relationship between lesion formation and abscisic acid (ABA synthesis pathway is not reported. In the present study, we identified a rice mutant, lesion mimic mutant 9150 (lmm9150, exhibiting spontaneous cell death, pre-harvest sprouting, enhanced growth, and resistance to rice bacterial and blast diseases. Cell death in the mutant was accompanied with excessive accumulation of H2O2. Enhanced disease resistance was associated with cell death and upregulation of defense-related genes. Map-based cloning identified a G-to-A point mutation resulting in a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610 in lmm9150. Knock-out of OsABA2 through CRISPR/Cas9 led to phenotypes similar to those of lmm9150. Consistent with the function of OsABA2 in ABA biosynthesis, ABA level in the lmm9150 mutant was significantly reduced. Moreover, exogenous application of ABA could rescue all the mutant phenotypes of lmm9150. Taken together, our data linked ABA deficiency to cell death and provided insight into the role of ABA in rice disease resistance.

  9. Mutation in Rice Abscisic Acid2 Results in Cell Death, Enhanced Disease-Resistance, Altered Seed Dormancy and Development.

    Science.gov (United States)

    Liao, Yongxiang; Bai, Que; Xu, Peizhou; Wu, Tingkai; Guo, Daiming; Peng, Yongbin; Zhang, Hongyu; Deng, Xiaoshu; Chen, Xiaoqiong; Luo, Ming; Ali, Asif; Wang, Wenming; Wu, Xianjun

    2018-01-01

    Lesion mimic mutants display spontaneous cell death, and thus are valuable for understanding the molecular mechanism of cell death and disease resistance. Although a lot of such mutants have been characterized in rice, the relationship between lesion formation and abscisic acid (ABA) synthesis pathway is not reported. In the present study, we identified a rice mutant, lesion mimic mutant 9150 ( lmm9150 ), exhibiting spontaneous cell death, pre-harvest sprouting, enhanced growth, and resistance to rice bacterial and blast diseases. Cell death in the mutant was accompanied with excessive accumulation of H 2 O 2 . Enhanced disease resistance was associated with cell death and upregulation of defense-related genes. Map-based cloning identified a G-to-A point mutation resulting in a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610) in lmm9150 . Knock-out of OsABA2 through CRISPR/Cas9 led to phenotypes similar to those of lmm9150 . Consistent with the function of OsABA2 in ABA biosynthesis, ABA level in the lmm9150 mutant was significantly reduced. Moreover, exogenous application of ABA could rescue all the mutant phenotypes of lmm9150 . Taken together, our data linked ABA deficiency to cell death and provided insight into the role of ABA in rice disease resistance.

  10. Femoral head vascularisation in Legg-Calve-Perthes disease: comparison of dynamic gadolinium-enhanced subtraction MRI with bone scintigraphy

    International Nuclear Information System (INIS)

    Lamer, Sylvie; Dorgeret, Sophie; Brillet, Pierre-Yves; Hassan, Max; Sebag, Guy H.; Khairouni, Abdeslam; Mazda, Keyvan; Bacheville, Eric; Pennecot, Georges F.; Bloch, Juliette

    2002-01-01

    Heading AbstractBackground. It has been reported that MRI using a dynamic gadolinium-enhanced subtraction technique can allow the early identification of ischaemia and the pattern of revascularisation in Legg-Calve-Perthes (LCP) disease with increased spatial and contrast resolution. Therefore, dynamic gadolinium-enhanced subtraction (DGS) MRI may be a possible non-ionising substitute for bone scintigraphy.Objective. The purpose of this prospective study was to compare DGS MRI and bone scintigraphy in the assessment of femoral head perfusion in LCP disease.Materials and methods. Twenty-six DGS MR images and bone scintigraphies of 25 hips in 23 children were obtained at different stages of LCP disease; three stage I, 12 stage II, six stage III and five stage IV (Waldenstroem classification). The extent of necrosis, epiphyseal revascularisation pathways (lateral pillar, medial pillar, and/or transphyseal perfusion) and metaphyseal changes were analysed.Results. Total agreement between both techniques was noted in the depiction of epiphyseal necrosis (kappa=1), and metaphyseal abnormalities (kappa=0.9). DGS MRI demonstrated better revascularisation in the lateral (kappa=0.62) and medial pillars (kappa=0.52). The presence of basal transphyseal reperfusion was more conspicuous with MRI.Conclusions. DGS MRI allows early detection of epiphyseal ischaemia and accurate analysis of the different revascularisation patterns. These changes are directly related to the prognosis of LCP disease and can aid therapeutic decision making. (orig.)

  11. Enhancing memory performance after organic brain disease relies on retrieval processes rather than encoding or consolidation

    NARCIS (Netherlands)

    Hildebrandt, H.; Gehrmann, A.; Mödden, C.; Eling, P.A.T.M.

    2011-01-01

    Neuropsychological rehabilitation of memory performance is still a controversial topic, and rehabilitation studies have not analyzed to which stage of memory processing (encoding, consolidation, or retrieval) enhancement may be attributed. We first examined the efficacy of a computer training

  12. Dynamic contrast-enhanced MRI improves accuracy for detecting focal splenic involvement in children and adolescents with Hodgkin disease

    Energy Technology Data Exchange (ETDEWEB)

    Punwani, Shonit; Taylor, Stuart A.; Halligan, Steve [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospital, Department of Radiology, London (United Kingdom); Cheung, King Kenneth; Skipper, Nicholas [University College London, Centre for Medical Imaging, London (United Kingdom); Bell, Nichola; Humphries, Paul D. [University College London Hospital, Department of Radiology, London (United Kingdom); Bainbridge, Alan [University College London, Department of Medical Physics and Bioengineering, London (United Kingdom); Groves, Ashley M.; Hain, Sharon F.; Ben-Haim, Simona [University College Hospital, Institute of Nuclear Medicine, London (United Kingdom); Shankar, Ananth; Daw, Stephen [University College London Hospital, Department of Paediatrics, London (United Kingdom)

    2013-08-15

    Accurate assessment of splenic disease is important for staging Hodgkin lymphoma. The purpose of this study was to assess T2-weighted imaging with and without dynamic contrast-enhanced (DCE) MRI for evaluation of splenic Hodgkin disease. Thirty-one children with Hodgkin lymphoma underwent whole-body T2-weighted MRI with supplementary DCE splenic imaging, and whole-body PET-CT before and following chemotherapy. Two experienced nuclear medicine physicians derived a PET-CT reference standard for splenic disease, augmented by follow-up imaging. Unaware of the PET-CT, two experienced radiologists independently evaluated MRI exercising a locked sequential read paradigm (T2-weighted then DCE review) and recorded the presence/absence of splenic disease at each stage. Performance of each radiologist was determined prior to and following review of DCE-MRI. Incorrect MRI findings were ascribed to reader (lesion present on MRI but missed by reader) or technical (lesion not present on MRI) error. Seven children had splenic disease. Sensitivity/specificity of both radiologists for the detection of splenic involvement using T2-weighted images alone was 57%/100% and increased to 100%/100% with DCE-MRI. There were three instances of technical error on T2-weighted imaging; all lesions were visible on DCE-MRI. T2-weighted imaging when complemented by DCE-MRI imaging may improve evaluation of Hodgkin disease splenic involvement. (orig.)

  13. Dynamic contrast-enhanced MRI improves accuracy for detecting focal splenic involvement in children and adolescents with Hodgkin disease

    International Nuclear Information System (INIS)

    Punwani, Shonit; Taylor, Stuart A.; Halligan, Steve; Cheung, King Kenneth; Skipper, Nicholas; Bell, Nichola; Humphries, Paul D.; Bainbridge, Alan; Groves, Ashley M.; Hain, Sharon F.; Ben-Haim, Simona; Shankar, Ananth; Daw, Stephen

    2013-01-01

    Accurate assessment of splenic disease is important for staging Hodgkin lymphoma. The purpose of this study was to assess T2-weighted imaging with and without dynamic contrast-enhanced (DCE) MRI for evaluation of splenic Hodgkin disease. Thirty-one children with Hodgkin lymphoma underwent whole-body T2-weighted MRI with supplementary DCE splenic imaging, and whole-body PET-CT before and following chemotherapy. Two experienced nuclear medicine physicians derived a PET-CT reference standard for splenic disease, augmented by follow-up imaging. Unaware of the PET-CT, two experienced radiologists independently evaluated MRI exercising a locked sequential read paradigm (T2-weighted then DCE review) and recorded the presence/absence of splenic disease at each stage. Performance of each radiologist was determined prior to and following review of DCE-MRI. Incorrect MRI findings were ascribed to reader (lesion present on MRI but missed by reader) or technical (lesion not present on MRI) error. Seven children had splenic disease. Sensitivity/specificity of both radiologists for the detection of splenic involvement using T2-weighted images alone was 57%/100% and increased to 100%/100% with DCE-MRI. There were three instances of technical error on T2-weighted imaging; all lesions were visible on DCE-MRI. T2-weighted imaging when complemented by DCE-MRI imaging may improve evaluation of Hodgkin disease splenic involvement. (orig.)

  14. Overexpression of a modified plant thionin enhances disease resistance to citrus canker and Huanglongbing (HLB)

    Science.gov (United States)

    Huanglongbing (HLB or citrus greening disease) caused by Candidatus Liberibacter asiaticus (Las) is a great threat to the United States citrus industry. There are no proven strategies to eliminate HLB disease and no cultivar has been identified with strong HLB resistance. Citrus canker is also an ec...

  15. Enhancement of soluble CD28 levels in the serum of Graves' disease.

    Science.gov (United States)

    Sun, Zhongwen; Yi, Lixian; Tao, Hong; Huang, Jingfang; Jin, Zhenghong; Xiao, Yang; Feng, Caiyun; Sun, Jing

    2014-01-01

    Graves' disease is an autoimmune disease of the thyroid gland mediated by T cells. CD28, a member of costimulatory molecules, plays a pivotal role in regulating T-cell responses. Plasma-soluble CD28 is one form of CD28 in peripheral blood. To investigate the concentrations of soluble CD28 in patients with Graves' disease, we used a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of CD28. Our results suggested that mean concentrations of soluble CD28 in plasma of patients with Graves' disease were 1.79 ±1.52 ng/ml, and levels of soluble CD28 in healthy subjects were only 0.83 ±1.35 ng/ml. Concentrations of soluble CD28 detected in patients with Graves' disease were significantly higher than those of healthy subjects (p Graves' disease. Therefore, aberrant elevation of plasma-soluble CD28 in patients with Graves' disease may reflect the dysregulation of immune system, and may serve as a useful biomarker in Graves' disease diagnosis.

  16. Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies

    DEFF Research Database (Denmark)

    Boyd, Mette; Thodberg, Malte; Vitezic, Morana

    2018-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal disorder, with two main types: Crohn's disease (CD) and ulcerative colitis (UC), whose molecular pathology is not well understood. The majority of IBD-associated SNPs are located in non-coding regions and are hard to characterize since...

  17. Deconstruction of Vulnerability to Complex Diseases: Enhanced Effect Sizes and Power of Intermediate Phenotypes

    Directory of Open Access Journals (Sweden)

    David Goldman

    2007-01-01

    Full Text Available The deconstruction of vulnerability to complex disease with the help of intermediate phenotypes, including the heritable and disease-associated endophenotypes, is a legacy of Henri Begleiter. Systematic searches for genes influencing complex disorders, including bipolar disorder, have recently been completed using whole genome association (WGA, identifying a series of validated loci. Using this information, it is possible to compare effect sizes of disease loci discovered in very large samples to the effect sizes of replicated functional loci determining intermediate phenotypes that are of essential interest in psychiatric disorders. It is shown that the genes influencing intermediate phenotypes tend to have a larger effect size. Furthermore, the WGA results reveal that the number of loci of large effect size for complex diseases is limited, and yet multiple functional loci have already been identified for intermediate phenotypes relevant to psychiatric diseases, and without the benefit of WGA.

  18. Frontal and temporal lobe contributions to emotional enhancement of memory in behavioural-variant frontotemporal dementia and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Fiona eKumfor

    2014-06-01

    Full Text Available Emotional events gain special priority in how they are remembered, with emotionally arousing events typically recalled more vividly and with greater confidence than non-emotional events. In dementia, memory and emotion processing are affected to varying degrees, however, whether emotional enhancement of memory for complex ecologically valid events is differentially affected across dementia syndromes remains unclear, with previous studies examining effects of emotion on simple visual recognition only. Here, we examined memory for an emotionally arousing short story and a closely matched, emotionally neutral story in behavioural-variant frontotemporal dementia (bvFTD (n = 13 and Alzheimer’s disease (AD (n = 14, and contrasted their performance with healthy controls (n = 12. Multiple-choice recognition memory for specific details of the story was assessed after a 1-hour delay. While AD and control groups showed enhanced memory for the emotional story, the bvFTD group recalled a similar number of details from the emotional and neutral stories. Voxel-based morphometry analyses revealed emotional enhancement of memory correlated with distinct brain regions in each patient group. In AD, emotional enhancement was associated with integrity of the bilateral hippocampus, parahippocampal gyri, temporal fusiform gyrus and frontal pole, regions implicated in memory processes. In contrast in bvFTD, integrity of emotion processing regions, including the orbitofrontal cortex, right amygdala and right insula, correlated with the extent emotion enhanced memory. Our results reveal that integrity of frontal and temporal regions determine the quality and nature of emotional memories. While emotional enhancement of memory is present in mild AD, in bvFTD emotion does not facilitate memory retrieval for complex realistic events. This attenuation of emotional enhancement is due to degradation of emotion processing regions, which may be important for modulating levels

  19. Application of low dose radiation and low concentration contrast media in enhanced CT scans in children with congenital heart disease.

    Science.gov (United States)

    Liu, Zhimin; Song, Lei; Yu, Tong; Gao, Jun; Zhang, Qifeng; Jiang, Ling; Liu, Yong; Peng, Yun

    2016-09-01

    The aim of this study was to explore the feasibility of using low dose radiation and low concentration contrast media in enhanced CT examinations in children with congenital heart disease. Ninety patients with congenital heart disease were randomly divided into three groups of 30 patients each who underwent contrast-enhanced cardiac scans on a Discovery CT750 HD scanner. Group A received 270 mg I/mL iodixanol, and group B received 320 mg I/mL iodixanol contrast media and was scanned with prospective ECG triggering mode. Group C received 320 mg I/mL iodixanol and was scanned with conventional retrospective ECG gating mode. The same weight-based contrast injection protocol was used for all three groups. Images were reconstructed using a 30% adaptive statistical iterative reconstruction (ASIR) algorithm and a 50% ASIR in groups A and B and a 30% ASIR in group C. The subjective and objective image quality evaluations, diagnostic accuracies, radiation doses and amounts of contrast media in the three groups were measured and compared. All images in the three groups met the diagnostic requirements, with the same diagnostic accuracy and image quality scores greater than 3 in a 4-point scoring system. However, ventricular enhancement and the objective noise, signal-to-noise ratio, contrast-to-noise ratio and subjective image quality scores in group C were better than those in groups A and B (all Pcontrast dose (14% lower than that of groups B and C). Enhanced CT scan images with low dose radiation and low concentration contrast media can meet the diagnostic requirements for examining children with congenital heart disease while reducing the potential risk of radiation damage and contrast-induced nephropathy. © 2016 John Wiley & Sons Ltd.

  20. Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Takamatsu, J.; Hosoya, T.; Naito, N.; Yoshimura, H.; Kohno, Y.; Tarutani, O.; Kuma, K.; Sakane, S.; Takeda, K.; Mozai, T.

    1988-01-01

    Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients. From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients. Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients. Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients.

  1. A Rationale for Music Training to Enhance Executive Functions in Parkinson’s Disease: An Overview of the Problem

    Directory of Open Access Journals (Sweden)

    Teresa Lesiuk

    2018-04-01

    Full Text Available Music listening interventions such as Rhythmic Auditory Stimulation can improve mobility, balance, and gait in Parkinson’s Disease (PD. Yet, the impact of music training on executive functions is not yet known. Deficits in executive functions (e.g., attention, processing speed in patients with PD result in gait interference, deficits in emotional processing, loss of functional capacity (e.g., intellectual activity, social participation, and reduced quality of life. The model of temporal prediction and timing suggests two networks collectively contribute to movement generation and execution: the basal ganglia-thalamocortical network (BGTC and the cerebellar-thalamocortical network (CTC. Due to decreases in dopamine responsible for the disruption of the BGTC network in adults with PD, it is hypothesized that rhythmic auditory cues assist patients through recruiting an alternate network, the CTC, which extends to the supplementary motor areas (SMA and the frontal cortices. In piano training, fine motor finger movements activate the cerebellum and SMA, thereby exercising the CTC network. We hypothesize that exercising the CTC network through music training will contribute to enhanced executive functions. Previous research suggested that music training enhances cognitive performance (i.e., working memory and processing speed in healthy adults and adults with cognitive impairments. This review and rationale provides support for the use of music training to enhance cognitive outcomes in patients with Parkinson’s Disease (PD.

  2. Enhancing patient engagement in chronic disease self-management support initiatives in Australia: the need for an integrated approach.

    Science.gov (United States)

    Jordan, Joanne E; Briggs, Andrew M; Brand, Caroline A; Osborne, Richard H

    2008-11-17

    Although emphasis on the prevention of chronic disease is important, governments in Australia need to balance this with continued assistance to the 77% of Australians reported to have at least one long-term medical condition. Self-management support is provided by health care and community services to enhance patients' ability to care for their chronic conditions in a cooperative framework. In Australia, there is a range of self-management support initiatives that have targeted patients (most notably, chronic disease self-management education programs) and health professionals (financial incentives, education and training). To date, there has been little coordination or integration of these self-management initiatives to enhance the patient-health professional clinical encounter. If self-management support is to work, there is a need to better understand the infrastructure, systems and training that are required to engage the key stakeholders - patients, carers, health professionals, and health care organisations. A coordinated approach is required in implementing these elements within existing and new health service models to enhance uptake and sustainability.

  3. A Rationale for Music Training to Enhance Executive Functions in Parkinson's Disease: An Overview of the Problem.

    Science.gov (United States)

    Lesiuk, Teresa; Bugos, Jennifer A; Murakami, Brea

    2018-04-22

    Music listening interventions such as Rhythmic Auditory Stimulation can improve mobility, balance, and gait in Parkinson’s Disease (PD). Yet, the impact of music training on executive functions is not yet known. Deficits in executive functions (e.g., attention, processing speed) in patients with PD result in gait interference, deficits in emotional processing, loss of functional capacity (e.g., intellectual activity, social participation), and reduced quality of life. The model of temporal prediction and timing suggests two networks collectively contribute to movement generation and execution: the basal ganglia-thalamocortical network (BGTC) and the cerebellar-thalamocortical network (CTC). Due to decreases in dopamine responsible for the disruption of the BGTC network in adults with PD, it is hypothesized that rhythmic auditory cues assist patients through recruiting an alternate network, the CTC, which extends to the supplementary motor areas (SMA) and the frontal cortices. In piano training, fine motor finger movements activate the cerebellum and SMA, thereby exercising the CTC network. We hypothesize that exercising the CTC network through music training will contribute to enhanced executive functions. Previous research suggested that music training enhances cognitive performance (i.e., working memory and processing speed) in healthy adults and adults with cognitive impairments. This review and rationale provides support for the use of music training to enhance cognitive outcomes in patients with Parkinson’s Disease (PD).

  4. Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease is Enhanced by Nrf2 Agonists.

    NARCIS (Netherlands)

    Bewley, Martin A; Budd, Richard C; Ryan, Eilise; Cole, Joby; Collini, Paul; Marshall, Jennifer; Kolsum, Umme; Beech, Gussie; Emes, Richard D; Tcherniaeva, Irina; Berbers, Guy A M; Walmsley, Sarah R; Donaldson, Gavin; Wedzicha, Jadwiga A; Kilty, Iain; Rumsey, William; Sanchez, Yolanda; Brightling, Christopher E; Donnelly, Louise E; Barnes, Peter J; Singh, Dave; Whyte, Moira K B; Dockrell, David H

    2018-01-01

    Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined.

  5. Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation.

    Directory of Open Access Journals (Sweden)

    Suan-Sin Foo

    2015-02-01

    Full Text Available The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV and Ross River virus (RRV, and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3 was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/- mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.

  6. Improving the dictionary lookup approach for disease normalization using enhanced dictionary and query expansion.

    Science.gov (United States)

    Jonnagaddala, Jitendra; Jue, Toni Rose; Chang, Nai-Wen; Dai, Hong-Jie

    2016-01-01

    The rapidly increasing biomedical literature calls for the need of an automatic approach in the recognition and normalization of disease mentions in order to increase the precision and effectivity of disease based information retrieval. A variety of methods have been proposed to deal with the problem of disease named entity recognition and normalization. Among all the proposed methods, conditional random fields (CRFs) and dictionary lookup method are widely used for named entity recognition and normalization respectively. We herein developed a CRF-based model to allow automated recognition of disease mentions, and studied the effect of various techniques in improving the normalization results based on the dictionary lookup approach. The dataset from the BioCreative V CDR track was used to report the performance of the developed normalization methods and compare with other existing dictionary lookup based normalization methods. The best configuration achieved an F-measure of 0.77 for the disease normalization, which outperformed the best dictionary lookup based baseline method studied in this work by an F-measure of 0.13.Database URL: https://github.com/TCRNBioinformatics/DiseaseExtract. © The Author(s) 2016. Published by Oxford University Press.

  7. Improving the dictionary lookup approach for disease normalization using enhanced dictionary and query expansion

    Science.gov (United States)

    Jonnagaddala, Jitendra; Jue, Toni Rose; Chang, Nai-Wen; Dai, Hong-Jie

    2016-01-01

    The rapidly increasing biomedical literature calls for the need of an automatic approach in the recognition and normalization of disease mentions in order to increase the precision and effectivity of disease based information retrieval. A variety of methods have been proposed to deal with the problem of disease named entity recognition and normalization. Among all the proposed methods, conditional random fields (CRFs) and dictionary lookup method are widely used for named entity recognition and normalization respectively. We herein developed a CRF-based model to allow automated recognition of disease mentions, and studied the effect of various techniques in improving the normalization results based on the dictionary lookup approach. The dataset from the BioCreative V CDR track was used to report the performance of the developed normalization methods and compare with other existing dictionary lookup based normalization methods. The best configuration achieved an F-measure of 0.77 for the disease normalization, which outperformed the best dictionary lookup based baseline method studied in this work by an F-measure of 0.13. Database URL: https://github.com/TCRNBioinformatics/DiseaseExtract PMID:27504009

  8. Gadolinium-enhanced MR angiography of arterial occlusive disease in lower extremity : comparison with conventional digital subtraction angiography

    International Nuclear Information System (INIS)

    Shin, Sang June; Koh, Young Hwan; Cha, Joo Hee; Kim, Hyu Beom; Chung, Jin Wook; Park, Jae Hyung

    2000-01-01

    To compare the diagnostic value of gadolinium-enhanced MR angiography with that of conventional digital subtraction angiography for the evaluation of lower extremity arterial occlusive diseases. In 26 patients with symptomatic lower extremity arterial occlusive disease, both conventional digital subtraction angiography (DSA) and gadolinium-enhanced MR angiography (CE-MRA) were performed during the same week. MR angiography was performed using three-dimensional gradient-echo acquisition before, and two sequential acquisitions after, the administration of gadolinium (0.2 mmol/kg). In 23 patients, two separate, contiguous areas were scanned using additional doses. In three patients, only one field with a suspicious lesion was scanned. Three radiologists independently analyzed the CE-MRA and DSA findings of each vascular segment (20 segments per arterial tree) for the presence of obstructive lesions; the grade assigned was either mild or none (less than 50%), stenotic (50%-99%), or occlusion (100%). From among a total of 462 segments, DSA detected 99 which were significantly narrowed (stenosis, 33; occlusion, 66). Using MR angiography, 102 segments (stenosis 39; occlusion, 63) were identified, and 94 lesions (stenosis, 32; occlusion, 62) were graded correctly. Seven lesions were overestimated and four were underestimated. For the detection of hemodynamically significant stenosis or occlusions using MR angiography, sensitivity, specificity, and diagnostic accuracy were 95%, 98%, and 98% (G=3D0.995, P less than 0.001), respectively. To prove the absence of lesions, we repeated DSA in two patients with arterial spasm due to puncture. Three occluded segments seen on DSA, which revealed intact segments on MR angiography, suggested slow distal flow after reconstitution. For the evaluation of lower extremity arterial occlusive disease, the diagnostic value of gadolinium-enhanced MR angiography is comparable with that of digital subtraction angiography. The advantages of the

  9. A double closed loop to enhance the quality of life of Parkinson's Disease patients: REMPARK system.

    Science.gov (United States)

    Samà, Albert; Pérez-López, Carlos; Rodríguez-Martín, Daniel; Moreno-Aróstegui, J Manuel; Rovira, Jordi; Ahlrichs, Claas; Castro, Rui; Cevada, João; Graça, Ricardo; Guimarães, Vânia; Pina, Bernardo; Counihan, Timothy; Lewy, Hadas; Annicchiarico, Roberta; Bayés, Angels; Rodríguez-Molinero, Alejandro; Cabestany, Joan

    2014-01-01

    This paper presents REMPARK system, a novel approach to deal with Parkinson's Disease (PD). REMPARK system comprises two closed loops of actuation onto PD. The first loop consists in a wearable system that, based on a belt-worn movement sensor, detects movement alterations that activate an auditory cueing system controlled by a smartphone in order to improve patient's gait. The belt-worn sensor analyzes patient's movement through real-time learning algorithms that were developed on the basis of a database previously collected from 93 PD patients. The second loop consists in disease management based on the data collected during long periods and that enables neurologists to tailor medication of their PD patients and follow the disease evolution. REMPARK system is going to be tested in 40 PD patients in Spain, Ireland, Italy and Israel. This paper describes the approach followed to obtain this system, its components, functionalities and trials in which the system will be validated.

  10. Synergies between Communicable and Noncommunicable Disease Programs to Enhance Global Health Security.

    Science.gov (United States)

    Kostova, Deliana; Husain, Muhammad J; Sugerman, David; Hong, Yuling; Saraiya, Mona; Keltz, Jennifer; Asma, Samira

    2017-12-01

    Noncommunicable diseases are the leading cause of death and disability worldwide. Initiatives that advance the prevention and control of noncommunicable diseases support the goals of global health security in several ways. First, in addressing health needs that typically require long-term care, these programs can strengthen health delivery and health monitoring systems, which can serve as necessary platforms for emergency preparedness in low-resource environments. Second, by improving population health, the programs might help to reduce susceptibility to infectious outbreaks. Finally, in aiming to reduce the economic burden associated with premature illness and death from noncommunicable diseases, these initiatives contribute to the objectives of international development, thereby helping to improve overall country capacity for emergency response.

  11. Efficacy of cognitive enhancers for Alzheimer’s disease: protocol for a systematic review and network meta-analysis

    Directory of Open Access Journals (Sweden)

    Tricco Andrea C

    2012-06-01

    Full Text Available Abstract Background Approximately 35 million people world-wide have Alzheimer’s disease and this is projected to nearly double by 2030. Cognitive enhancers, including cholinesterase inhibitors (for example, donepezil, galantamine and rivastigmine and memantine (N-methyl-D-aspartic acid (NMDA receptor antagonist have been approved for the treatment of Alzheimer’s disease in many countries. Our objective is to evaluate the comparative effectiveness, safety, and cost of cognitive enhancers for Alzheimer’s disease through a systematic review. Methods/design Studies examining the efficacy, safety, and cost of cognitive enhancers compared to placebo, supportive care, and other cognitive enhancers for Alzheimer’s patients will be included. The primary outcome is cognition and secondary outcomes include function, behavior, quality of life, safety, and cost. Experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, quasi-experimental studies (controlled before-after, interrupted time series, and observational studies (cohort, case–control studies will be eligible for inclusion. Inclusion will not be limited by publication status, time period or language of dissemination. We will search electronic databases (for example, MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Ageline from inception onwards. The electronic database search will be supplemented by searching for grey literature (for example, conference proceedings, searches in Google and relevant organization websites. Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational studies. If deemed appropriate, meta-analysis and network (that is, indirect

  12. IFN-{gamma} enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Baron, Rona; Nemirovsky, Anna; Harpaz, Idan

    2008-01-01

    the spatial learning and memory performance of the animals. In older mice, the effect of IFN-gamma is more pronounced in both wild-type mice and mice with Alzheimer's-like disease and is associated with neuroprotection. In addition, IFN-gamma reverses the increase in oligodendrogenesis observed in a mouse...... mechanisms can generate immunity to such deficits in neuronal repair. We demonstrate that in contrast to primarily innate immunity cytokines, such as interleukin-6 and tumor necrosis factor-alpha, the adaptive immunity cytokine IFN-gamma enhances neurogenesis in the dentate gyrus of adult mice and improves...

  13. Enhancing prescribing of guideline-recommended medications for ischaemic heart diseases: a systematic review and meta-analysis of interventions targeted at healthcare professionals

    NARCIS (Netherlands)

    Nguyen, Thang; Nguyen, Hoa Q; Widyakusuma, Niken N; Nguyen, Thao H; Pham, Tam T; Taxis, Katja

    Objectives Ischaemic heart diseases (IHDs) are a leading cause of death worldwide. Although prescribing according to guidelines improves health outcomes, it remains suboptimal. We determined whether interventions targeted at healthcare professionals are effective to enhance prescribing and health

  14. Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease.

    Science.gov (United States)

    Lottaz, Daniel; Buri, Caroline; Monteleone, Giovanni; Rösmann, Sandra; Macdonald, Thomas T; Sanderson, Ian R; Sterchi, Erwin E

    2007-03-01

    Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epithelium.

  15. Test-Enhanced Learning in an Immunology and Infectious Disease Medicinal Chemistry/Pharmacology Course.

    Science.gov (United States)

    Hernick, Marcy

    2015-09-25

    Objective. To develop a series of active-learning modules that would improve pharmacy students' performance on summative assessments. Design. A series of optional online active-learning modules containing questions with multiple formats for topics in a first-year (P1) course was created using a test-enhanced learning approach. A subset of module questions was modified and included on summative assessments. Assessment. Student performance on module questions improved with repeated attempts and was predictive of student performance on summative assessments. Performance on examination questions was higher for students with access to modules than for those without access to modules. Module use appeared to have the most impact on low performing students. Conclusion. Test-enhanced learning modules with immediate feedback provide pharmacy students with a learning tool that improves student performance on summative assessments and also may improve metacognitive and test-taking skills.

  16. Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor–mediated disease

    Science.gov (United States)

    Chua, Jason P.; Reddy, Satya L.; Yu, Zhigang; Giorgetti, Elisa; Montie, Heather L.; Mukherjee, Sarmistha; Higgins, Jake; McEachin, Richard C.; Robins, Diane M.; Merry, Diane E.; Iñiguez-Lluhí, Jorge A.; Lieberman, Andrew P.

    2015-01-01

    Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that are sites of SUMOylation. We determined that replacement of these residues by arginine enhances polyQ AR activity as a hormone-dependent transcriptional regulator. In a murine model, disruption of polyQ AR SUMOylation rescued exercise endurance and type I muscle fiber atrophy; it also prolonged survival. These changes occurred without overt alterations in polyQ AR expression or aggregation, revealing the favorable trophic support exerted by the ligand-activated receptor. Our findings demonstrate beneficial effects of enhancing the transcriptional function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may be a potential target for therapeutic intervention in SBMA. PMID:25607844

  17. Liquid culture enhances diagnosis of patients with milder forms of non-tuberculous mycobacterial lung disease.

    Science.gov (United States)

    Lee, H; Han, J-H; Park, H Y; Jeon, K; Huh, H J; Ki, C-S; Lee, N Y; Koh, W-J

    2017-03-01

    To evaluate the proportion and clinical characteristics of patients with non-tuberculous mycobacteria (NTM) lung disease diagnosed based on positive culture results in liquid medium only. We reviewed the medical records of 978 patients diagnosed with NTM lung disease. All clinical samples were cultured in both solid and liquid media. Of the 978 patients, 111 (11.3%) were culture-positive in liquid medium only (liquid culture group), and 867 (88.7%) (solid culture group) on solid medium, regardless of the culture results in liquid medium. At the time of diagnosis, the liquid culture group was less likely than the solid culture group to have haemoptysis (11.7% vs. 20.0%, P = 0.04), positive sputum smear for acid-fast bacilli (14.4% vs. 50.2%, P disease (3.6% vs. 14.6%, P = 0.001). During the median follow-up period of 28.9 months (interquartile range 19.1-41.6), the proportion of patients requiring antibiotic treatment was lower in the liquid culture group than in the solid culture group (44.1% vs. 61.6%, P culture is helpful in the diagnosis of patients with less severe forms of NTM lung disease.

  18. The role of dynamic contrast enhanced MRI in diagnosis of the Hirayama disease

    International Nuclear Information System (INIS)

    Georgieva-Kozarova, G.; Penev, L.; Petrova, M.; Grigorova, O.; Traykov, L.

    2013-01-01

    Hirayama disease (HD) is a very rare condition characterized by asymmetric distal upper limbs muscle weakness and atrophy in the C8-T1 distribution without sensory or pyramidal signs. Classically, adolescent males develop initially progressive weakness followed by spontaneous stabilization within several years after onset. The pathogenesis of the disease is unclear and pathologic studies are lacking. However the prevailing theory postulates that insufficient growth of the dura relative to the spinal column during puberty allows forward displacement of the dura in flexion with compression of the spinal cord, possibly leading to ischemia of the anterior horn cells at C8 and Th1. Most reported cases have been from Asia, particularly Japan, though some have been reported from India, the Middle East, and Europe. To date, and to our knowledge, there has been no published study characterizing the MR imaging features of this disease in Bulgaria. Routine MR imaging of patients with HD has shown segmental cord atrophy, rarely associated with Th2 abnormalities. Previous studies of other cord diseases have shown, that the extent of cord tissue damage is usually underestimated by using routine MR imaging and that brain plasticity might limit the clinical consequences of cord injury. In this study, we used a multi-parametric MR imaging approach to investigate in a patient with HD. (authors)

  19. GmPGIP3 enhanced resistance to both take-all and common root rot diseases in transgenic wheat.

    Science.gov (United States)

    Wang, Aiyun; Wei, Xuening; Rong, Wei; Dang, Liang; Du, Li-Pu; Qi, Lin; Xu, Hui-Jun; Shao, Yanjun; Zhang, Zengyan

    2015-05-01

    Take-all (caused by the fungal pathogen Gaeumannomyces graminis var. tritici, Ggt) and common root rot (caused by Bipolaris sorokiniana) are devastating root diseases of wheat (Triticum aestivum L.). Development of resistant wheat cultivars has been a challenge since no resistant wheat accession is available. GmPGIP3, one member of polygalacturonase-inhibiting protein (PGIP) family in soybean (Glycine max), exhibited inhibition activity against fungal endopolygalacturonases (PGs) in vitro. In this study, the GmPGIP3 transgenic wheat plants were generated and used to assess the effectiveness of GmPGIP3 in protecting wheat from the infection of Ggt and B. sorokiniana. Four independent transgenic lines were identified by genomic PCR, Southern blot, and reverse transcription PCR (RT-PCR). The introduced GmPGIP3 was integrated into the genomes of these transgenic lines and could be expressed. The expressing GmPGIP3 protein in these transgenic wheat lines could inhibit the PGs produced by Ggt and B. sorokiniana. The disease response assessments postinoculation showed that the GmPGIP3-expressing transgenic wheat lines displayed significantly enhanced resistance to both take-all and common root rot diseases caused by the infection of Ggt and B. sorokiniana. These data suggested that GmPGIP3 is an attractive gene resource in improving resistance to both take-all and common root rot diseases in wheat.

  20. FOCAL ENHANCED GASTRITIS AND MACROPHAGE MICROAGGREGATES IN THE GASTRIC MUCOSA: potential role in the differential diagnosis between Crohn’s disease and ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Marcia Henriques de MAGALHÃES-COSTA

    2014-12-01

    Full Text Available Context and Objectives Focally enhanced gastritis and macrophage microaggregates are found in the upper gastrointestinal involvement of Crohn’s disease, and may reflect an underlying defective innate immunity. These features, however, are also described in patients with Helicobacter pylori infection. The role of these gastric abnormalities in the diagnosis of Crohn’s disease was assessed in a population with high prevalence of H. pylori infection. Methods Thirty-seven Crohn’s disease, 26 ulcerative colitis, and 30 control patients were included. The H. pylori status was evaluated by the rapid urease test and histology. The presence of focally enhanced gastritis and macrophage microaggregates was recorded. Results Focally enhanced gastritis was present in 24% of Crohn’s disease patients, 4% of ulcerative colitis patients and 11.5% of controls, presenting an overall sensitivity and specificity for Crohn’s disease of 24% and 88%, respectively. Macrophage microaggregates were found in all groups, but were only detected in ulcerative colitis and controls in association with H. pylori infection, with an overall sensitivity and specificity for Crohn’s disease of 61% and 69%, respectively. In the absence of H. pylori infection, focally enhanced gastritis and macrophage microaggregates were significantly associated with Crohn’s disease (P<0.02 and P = 0.001 respectively. Conclusions Focally gastritis and macrophage microaggregates are suggestive of Crohn’s disease only in H. pylori-negative specimens. HEADINGS - Crohn’s disease. Ulcerative colitis. Gastritis. Macrophages. Helicobacter pylori.

  1. Cognitive enhancers (nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. disease-modifying drugs.

    Science.gov (United States)

    Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

    2013-01-01

    Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

  2. Contrast-enhanced magnetic resonance angiography in carotid artery disease: does automated image registration improve image quality?

    International Nuclear Information System (INIS)

    Menke, Jan; Larsen, Joerg

    2009-01-01

    Contrast-enhanced magnetic resonance angiography (MRA) is a noninvasive imaging alternative to digital subtraction angiography (DSA) for patients with carotid artery disease. In DSA, image quality can be improved by shifting the mask image if the patient has moved during angiography. This study investigated whether such image registration may also help to improve the image quality of carotid MRA. Data from 370 carotid MRA examinations of patients likely to have carotid artery disease were prospectively collected. The standard nonregistered MRAs were compared to automatically linear, affine and warp registered MRA by using three image quality parameters: the vessel detection probability (VDP) in maximum intensity projection (MIP) images, contrast-to-noise ratio (CNR) in MIP images, and contrast-to-noise ratio in three-dimensional image volumes. A body shift of less than 1 mm occurred in 96.2% of cases. Analysis of variance revealed no significant influence of image registration and body shift on image quality (p > 0.05). In conclusion, standard contrast-enhanced carotid MRA usually requires no image registration to improve image quality and is generally robust against any naturally occurring body shift. (orig.)

  3. Google Calendar Enhances Prospective Memory in Alzheimer's Disease: A Case Report.

    Science.gov (United States)

    El Haj, Mohamad; Gallouj, Karim; Antoine, Pascal

    2017-01-01

    We investigated whether an external memory aid (i.e., Google Calendar) would alleviate prospective memory compromise in a patient with mild Alzheimer's disease. The patient was asked in the baseline phase to perform three prospective targeted events (e.g., attending her weekly bridge game at the community club) and three prospective control events (e.g., buying her weekly magazine). The same six prospective events were assessed in the intervention phase but the targeted-events were cued by Google Calendar while the control-events were not. Results showed less omission of the targeted events in the training phase than in the baseline phase, suggesting a positive effect of Google Calendar. This case report offers a unique view into how smartphone calendars may alleviate prospective memory compromise in patients with mild Alzheimer's disease.

  4. Familiar Music as an Enhancer of Self-Consciousness in Patients with Alzheimer’s Disease

    OpenAIRE

    Arroyo-Anlló, Eva M.; Díaz, Juan Poveda; Gil, Roger

    2013-01-01

    The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC) in patients with Alzheimer's disease (AD). For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspec...

  5. Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults with Autoimmune Inflammatory Diseases.

    Science.gov (United States)

    Kirchner, Elizabeth; Ruffing, Victoria

    2017-02-01

    For as long as there have been immunizations, there have been barriers to them. Immunization rates in the United States are below target. Rheumatologists and rheumatology practitioners need to understand the issues of immunizations in patients with autoimmune inflammatory disease to identify and overcome barriers to immunization. Several strategies for overcoming these barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3

    Science.gov (United States)

    Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno

    2014-02-01

    Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.

  7. Enhanced sensitivity in detection of antiviral antibody responses using biotinylation of foot-and-mouth disease virus (FMDV) capsids.

    Science.gov (United States)

    Kenney, Mary; Waters, Ryan A; Rieder, Elizabeth; Pega, Juan; Perez-Filguera, Mariano; Golde, William T

    2017-11-01

    Analysis of the immune response to infection of livestock by foot-and-mouth disease virus (FMDV) is most often reported as the serum antibody response to the virus. While measurement of neutralizing antibody has been sensitive and specific, measurements of the quality of the antibody response are less robust. Determining the immunoglobulin (Ig) isotype of the serum antibody response provides a deeper understanding of the biology of the response and more sensitive methods for these assays will facilitate analyses of B cell mediated immunity. We tested the hypothesis that using the virus as the molecular probe could be achieved by adding tags to the surface of the FMDV capsid, and that would enhance sensitivity in assays for anti-FMDV antibody responses. The use of a FLAG-tagged virus in these assays failed to yield improvement whereas chemically biotinylating the virus capsid resulted in significant enhancement of the signal. Here we describe methods using biotinylated virus for measuring anti-viral antibody in serum and antibody secreting cells (ASCs) in blood that are sensitive and specific. Finally, we describe using the biotinylated virus in flow cytometry where such assays should greatly enhance the analysis of anti-virus antibody producing B cells, allowing the investigator to focus on only the FMDV specific B cells when analyzing the development of the B cell response to either infection or vaccination. Published by Elsevier B.V.

  8. Enhanced disease resistance and drought tolerance in transgenic rice plants overexpressing protein elicitors from Magnaporthe oryzae.

    Science.gov (United States)

    Wang, Zhenzhen; Han, Qiang; Zi, Qian; Lv, Shun; Qiu, Dewen; Zeng, Hongmei

    2017-01-01

    Exogenous application of the protein elicitors MoHrip1 and MoHrip2, which were isolated from the pathogenic fungus Magnaporthe oryzae (M. oryzae), was previously shown to induce a hypersensitive response in tobacco and to enhance resistance to rice blast. In this work, we successfully transformed rice with the mohrip1 and mohrip2 genes separately. The MoHrip1 and MoHrip2 transgenic rice plants displayed higher resistance to rice blast and stronger tolerance to drought stress than wild-type (WT) rice and the vector-control pCXUN rice. The expression of salicylic acid (SA)- and abscisic acid (ABA)-related genes was also increased, suggesting that these two elicitors may trigger SA signaling to protect the rice from damage during pathogen infection and regulate the ABA content to increase drought tolerance in transgenic rice. Trypan blue staining indicated that expressing MoHrip1 and MoHrip2 in rice plants inhibited hyphal growth of the rice blast fungus. Relative water content (RWC), water usage efficiency (WUE) and water loss rate (WLR) were measured to confirm the high capacity for water retention in transgenic rice. The MoHrip1 and MoHrip2 transgenic rice also exhibited enhanced agronomic traits such as increased plant height and tiller number.

  9. Focal enhanced gastritis and macrophage microaggregates in the gastric mucosa: potential role in the differential diagnosis between Crohn's disease and ulcerative colitis.

    Science.gov (United States)

    Magalhães-Costa, Marcia Henriques de; Reis, Beatriz Ribeiro dos; Chagas, Vera Lúcia Antunes; Nunes, Tiago; Souza, Heitor Siffert Pereira de; Zaltman, Cyrla

    2014-01-01

    Focally enhanced gastritis and macrophage microaggregates are found in the upper gastrointestinal involvement of Crohn's disease, and may reflect an underlying defective innate immunity. These features, however, are also described in patients with Helicobacter pylori infection. The role of these gastric abnormalities in the diagnosis of Crohn's disease was assessed in a population with high prevalence of H. pylori infection. Thirty-seven Crohn's disease, 26 ulcerative colitis, and 30 control patients were included. The H. pylori status was evaluated by the rapid urease test and histology. The presence of focally enhanced gastritis and macrophage microaggregates was recorded. Focally enhanced gastritis was present in 24% of Crohn's disease patients, 4% of ulcerative colitis patients and 11.5% of controls, presenting an overall sensitivity and specificity for Crohn's disease of 24% and 88%, respectively. Macrophage microaggregates were found in all groups, but were only detected in ulcerative colitis and controls in association with H. pylori infection, with an overall sensitivity and specificity for Crohn's disease of 61% and 69%, respectively. In the absence of H. pylori infection, focally enhanced gastritis and macrophage microaggregates were significantly associated with Crohn's disease (Pgastritis and macrophage microaggregates are suggestive of Crohn's disease only in H. pylori-negative specimens.

  10. In Vitro Synergistic Enhancement of Newcastle Disease Virus to 5-Fluorouracil Cytotoxicity against Tumor Cells

    Directory of Open Access Journals (Sweden)

    Ahmed M. Al-Shammari

    2016-01-01

    Full Text Available Background: Chemotherapy is one of the antitumor therapies used worldwide in spite of its serious side effects and unsatisfactory results. Many attempts have been made to increase its activity and reduce its toxicity. 5-Fluorouracil (5-FU is still a widely-used chemotherapeutic agent, especially in combination with other chemotherapies. Combination therapy seems to be the best option for targeting tumor cells by different mechanisms. Virotherapy is a promising agent for fighting cancer because of its safety and selectivity. Newcastle disease virus is safe, and it selectively targets tumor cells. We previously demonstrated that Newcastle disease virus (NDV could be used to augment other chemotherapeutic agents and reduce their toxicity by halving the administered dose and replacing the eliminated chemotherapeutic agents with the Newcastle disease virus; the same antitumor activity was maintained. Methods: In the current work, we tested this hypothesis on different tumor cell lines. We used the non-virulent LaSota strain of NDV in combination with 5-FU, and we measured the cytotoxicity effect. We evaluated this combination using Chou–Talalay analysis. Results: NDV was synergistic with 5-FU at low doses when used as a combination therapy on different cancer cells, and there were very mild effects on non-cancer cells. Conclusion: The combination of a virulent, non-pathogenic NDV–LaSota strain with a standard chemotherapeutic agent, 5-FU, has a synergistic effect on different tumor cells in vitro, suggesting this combination could be an important new adjuvant therapy for treating cancer.

  11. Enhancing Effect of Hydroxyurea on Hb F in Sickle Cell Disease: Ten-Year Egyptian Experience.

    Science.gov (United States)

    Youssry, Ilham; Abdel-Salam, Amina; Ismail, Rania; Bou-Fakhredin, Rayan; Mohamed Samy, Rania; Ezz El-Deen, Fatma; Taher, Ali T

    Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.

  12. Argument-predicate distance as a filter for enhancing precision in extracting predications on the genetic etiology of disease

    Directory of Open Access Journals (Sweden)

    Lang François-Michel

    2006-06-01

    Full Text Available Abstract Background Genomic functional information is valuable for biomedical research. However, such information frequently needs to be extracted from the scientific literature and structured in order to be exploited by automatic systems. Natural language processing is increasingly used for this purpose although it inherently involves errors. A postprocessing strategy that selects relations most likely to be correct is proposed and evaluated on the output of SemGen, a system that extracts semantic predications on the etiology of genetic diseases. Based on the number of intervening phrases between an argument and its predicate, we defined a heuristic strategy to filter the extracted semantic relations according to their likelihood of being correct. We also applied this strategy to relations identified with co-occurrence processing. Finally, we exploited postprocessed SemGen predications to investigate the genetic basis of Parkinson's disease. Results The filtering procedure for increased precision is based on the intuition that arguments which occur close to their predicate are easier to identify than those at a distance. For example, if gene-gene relations are filtered for arguments at a distance of 1 phrase from the predicate, precision increases from 41.95% (baseline to 70.75%. Since this proximity filtering is based on syntactic structure, applying it to the results of co-occurrence processing is useful, but not as effective as when applied to the output of natural language processing. In an effort to exploit SemGen predications on the etiology of disease after increasing precision with postprocessing, a gene list was derived from extracted information enhanced with postprocessing filtering and was automatically annotated with GFINDer, a Web application that dynamically retrieves functional and phenotypic information from structured biomolecular resources. Two of the genes in this list are likely relevant to Parkinson's disease but are not

  13. Functional role of an endophytic Bacillus amyloliquefaciens in enhancing growth and disease protection of invasive English ivy (Hedera helix L.)

    Science.gov (United States)

    Soares, Marcos Antonio; Li, Jai-Yan; Bergen, Marshall; da Silva, Joaquim Manoel; Kowalski, Kurt P.; White, James Francis

    2015-01-01

    BackgroundWe hypothesize that invasive English ivy (Hedera helix) harbors endophytic microbes that promote plant growth and survival. To evaluate this hypothesis, we examined endophytic bacteria in English ivy and evaluated effects on the host plant.MethodsEndophytic bacteria were isolated from multiple populations of English ivy in New Brunswick, NJ. Bacteria were identified as a single species Bacillus amyloliquefaciens. One strain of B. amyloliquefaciens, strain C6c, was characterized for indoleacetic acid (IAA) production, secretion of hydrolytic enzymes, phosphate solubilization, and antibiosis against pathogens. PCR was used to amplify lipopeptide genes and their secretion into culture media was detected by MALDI-TOF mass spectrometry. Capability to promote growth of English ivy was evaluated in greenhouse experiments. The capacity of C6c to protect plants from disease was evaluated by exposing B+ (bacterium inoculated) and B− (non-inoculated) plants to the necrotrophic pathogen Alternaria tenuissima.ResultsB. amyloliquefaciens C6c systemically colonized leaves, petioles, and seeds of English ivy. C6c synthesized IAA and inhibited plant pathogens. MALDI-TOF mass spectrometry analysis revealed secretion of antifungal lipopeptides surfactin, iturin, bacillomycin, and fengycin. C6c promoted the growth of English ivy in low and high soil nitrogen conditions. This endophytic bacterium efficiently controlled disease caused by Alternaria tenuissima.ConclusionsThis study suggests that B. amyloliquefaciens plays an important role in enhancing growth and disease protection of English ivy.

  14. The thoracic aortography by Gd-DTPA enhanced ultrafast cine MR imaging. Assessment of thoracic aortic dilatation in aging and in patients with hypertension and aortic valve disease

    International Nuclear Information System (INIS)

    Matsumura, Kentaro; Nakase, Emiko; Kawai, Ichiyoshi; Saito, Takayuki; Kikkawa, Nobutada; Haiyama, Toru

    1995-01-01

    To assess the morphology of thoracic aorta, we had a trial of Gd-DTPA enhanced ultrafast cine MR imaging on the thoracic aorta. This method was provided with high quality thoracic aortogram during 15-20 seconds. In patients without hypertension and aortic valve disease, dimensions of ascending aorta and aortic arch were significantly correlated with aging. In patients with hypertension, dimensions of ascending aorta and aortic arch were significantly dilated. In patients with aortic valve disease, thoracic aorta was diffusely enlarged, especially in ascending aorta. Gd-DTPA enhanced ultrafact cine MR imaging was useful to assess the thoracic aortic anatomy and diseases. (author)

  15. ENHANCED IMMUNIZATION COVERAGE THROUGH INTERVENTIONS FOR CHILDHOOD CLUSTER DISEASES IN DEVELOPING COUNTRIES.

    Science.gov (United States)

    Mureed, Sheh; Somronghtong, Ratana; Kumar, Ramesh; Ghaffar, Abdul; Chapman, Robert S

    2015-01-01

    Globally immunisation has to be considered as a most effective and efficient public health intervention to reduce morbidity and mortality among children. Most of the children from developing countries are still not fully immunized due to multiple factors including lack of interventions, awareness, and financial constraints and due to limited resource. Conversely, this review has identified the effectiveness of interventions to increase the immunisation coverage among children of developing countries. Systematic review by using PRISMA statement ("preferred reporting items for systematic reviews and meta-analyses") has been conducted in English. published articles on Pub Med, Scopus, Cochrane, Medline and ISI by searching keywords like immunizations, childhood vaccination and developing countries has been accessed. Only randomised controlled trial and quasi-experimental studies designs were included in the final analysis based on quality assessment by adopting the Down and Black checklist and finally pooled analysis was done by random effect model. This systematic review has been approved and registered by University of York. A total of 16,570 published articles were accessed and finally 10 fulfilled our criteria that were analysed and interpreted. It demonstrated that the interventions has shown significantly increase vaccine coverage for childhood cluster diseases (OR 2.136 and p 0.05) and full vaccination schedule (OR 1.342 and p>0.05). Systematic review has concluded that the professional interventions are an effective while in improving the child immunisation coverage for cluster diseases in developing countries, major effect on DTP an.d measles.

  16. Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery.

    Science.gov (United States)

    Scott, Eric M; Halees, Anason; Itan, Yuval; Spencer, Emily G; He, Yupeng; Azab, Mostafa Abdellateef; Gabriel, Stacey B; Belkadi, Aziz; Boisson, Bertrand; Abel, Laurent; Clark, Andrew G; Alkuraya, Fowzan S; Casanova, Jean-Laurent; Gleeson, Joseph G

    2016-09-01

    The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia, has resulted in an elevated burden of recessive disease. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized 'genetic purging'. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics.

  17. Can Children Enhance Their Family's Health Knowledge? An Infectious Disease Prevention Program.

    Science.gov (United States)

    Sedighi, Iraj; Nouri, Shahla; Sadrosadat, Taravat; Nemati, Reza; Shahbazi, Mojgan

    2012-12-01

    The purpose of this study is to propose an innovative method of knowledge transfer that aims to improve health literacy about pediatric infectious diseases prevention in families. Children have an appreciable role in this scheme. This study is a before and after trial that has been conducted in Hamedan in 2009. After changing seven infectious disease topics into childish poems, we selected five kindergartens randomly and taught these poetries to the children. Teaching process held after a pretest containing 24 questions that examined 103 of parents about mentioned topics. The same post-test was given after 4 months of teaching process. The mean of correct answers to the pretest was 59.22% comparable with 81.00% for post-test (P<0.00). Gender and knowledge degree could not change the results significantly. Assuming one's correct answers to the questions as his/her Knowledge Mark, the mean of this variable increased to 5.32 by this method. This cost-effective and joyful method had successful results in promoting health knowledge. Children are able to play an active role in family's health situation. Learning within family atmosphere without any obligations makes our scheme a solution for paving the knowledge transferring way.

  18. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

    Energy Technology Data Exchange (ETDEWEB)

    Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

    2000-10-01

    To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean {+-}S.D.: 0.87{+-}0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean {+-}S.D.: 0.34{+-}0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean {+-}S.D. 1.35{+-}0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean {+-}S.D.: 3.50{+-}2.51 %/min

  19. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

    International Nuclear Information System (INIS)

    Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo

    2000-01-01

    To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean ±S.D.: 0.87±0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean ±S.D.: 0.34±0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean ±S.D. 1.35±0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean ±S.D.: 3.50±2.51 %/min vs. 7.13±1

  20. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests

    Energy Technology Data Exchange (ETDEWEB)

    Kukuk, Guido M.; Schaefer, Stephanie G.; Hadizadeh, Dariusch R.; Schild, Hans H.; Willinek, Winfried A. [University of Bonn, Department of Radiology, Bonn (Germany); Fimmers, Rolf [University of Bonn, Department of Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Ezziddin, Samer [Department of Nuclear Medicine, Bonn (Germany); Spengler, Ulrich [Department of Internal Medicine I, Bonn (Germany)

    2014-10-15

    To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. (orig.)

  1. Oil-in-oil-emulsions with enhanced substantivity for the treatment of chronic skin diseases.

    Science.gov (United States)

    Lunter, Dominique Jasmin; Rottke, Michael; Daniels, Rolf

    2014-05-01

    The therapy of chronic skin diseases often requires several applications of creams or ointments per day. This is inconvenient to the patients and frequently leads to poor acceptance and compliance. We therefore developed oil-in-oil-emulsions that deliver the active pharmaceutical ingredient (API) to the skin over a prolonged period of time. In this study, we compare the permeation of the API from a conventional formulation to its permeation from an oil-in-oil-emulsion under infinite and finite dosing. Furthermore, we evaluate the substantivity of the formulations. Our results show that the permeation from oil-in-oil-emulsions is constant over a prolonged time and that the emulsions show significantly higher substantivity than conventional formulations. Because of that, the treatment intervals can be extended substantially and compliance can be increased. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Endogenous repair mechanisms enhanced in Parkinson's disease following stem cell therapy

    Directory of Open Access Journals (Sweden)

    Eleonora Napoli

    2017-01-01

    Full Text Available This mini-review highlights the innovative observation that transplanted human neural stem cells can bring about endogenous brain repair through the stimulation of multiple regenerative processes in the neurogenic area (i.e., subventricular zone [SVZ] in an animal model of Parkinson's disease (PD. In addition, we convey that identifying anti-inflammatory cytokines, therapeutic proteomes, and neurotrophic factors within the SVZ may be essential to induce brain repair and behavioral recovery. This work opens up a new area of research for further understanding the pathology and treatment of PD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  3. Enhanced parenting knowledge and skills in mothers of preschool children with sickle cell disease.

    Science.gov (United States)

    Schuman, W B; Armstrong, F D; Pegelow, C H; Routh, D K

    1993-10-01

    Compared 25 preschool children with sickle cell disease (SCD) to demographically matched healthy comparison children on maternal reports of child-rearing beliefs and practices and maternal and child behaviors related to social adjustment. Mothers of children with SCD possessed significantly more knowledge of appropriate discipline techniques. The groups did not differ on maternal reports of socially relevant child behavior. However, when mother-child interactions were observed in free play and structured play settings, mothers of children with SCD treated their children as competent significantly more, and treated their children as incompetent significantly less, than comparison mothers. Mothers of children with SCD also used significantly more reinforcement during the final toy pick-up condition. There were no observed differences between groups in the children's behavior.

  4. Ileal adhesion of virulent E. coli LF82 is not enhanced in Crohn’s disease

    DEFF Research Database (Denmark)

    Jensen, Rikke S.; Fink, Lisbeth Nielsen; Pedersen, Susanne Brix

    2011-01-01

    Adherent-invasive Escherichia coli (AIEC) comprise a new group of E. coli species named from their distinctive ability to adhere to and invade the intestinal epithelium. The AIEC strains have been associated to the ileal mucosa in Crohn’s disease (CD), and the impact of AIEC in the pathogenesis...... of CD has been further strengthened from the evidence that the ileum in CD harbors an abnormally high number of E. coli species. S16 2010 IBD Abstracts The aim of this study was to examine the adhesion of the AIEC reference strain, LF82, to tissue samples from ileum and colon in CD and healthy controls...... and comprised: 1) incubation of tissue (inclusive of mucous) with 107 bacteria or buffer for 1 hour, 2) removal of non-adhered bacteria by extensive washing, and 3) absolute quantification of tissue-adhered LF82 and indigenous E. coli by a pre-validated assay including quantitative real-time PCR. Selective...

  5. Enhanced immunization coverage through interventions for childhood cluster diseases in developing countries

    International Nuclear Information System (INIS)

    Mureed, S.; Somronghtong, R.; Kumar, R.

    2015-01-01

    Globally immunisation has to be considered as a most effective and efficient public health intervention to reduce morbidity and mortality among children. Most of the children from developing countries are still not fully immunized due to multiple factors including lack of interventions, awareness, and financial constraints and due to limited resource. Conversely, this review has identified the effectiveness of interventions to increase the immunisation coverage among children of developing countries. Methods: Systematic review by using PRISMA statement (preferred reporting items for systematic reviews and meta-analyses) has been conducted in English published articles on Pub Med, Scopus, Cochrane, Medline and ISI by searching keywords like immunizations, childhood vaccination and developing countries has been accessed. Only randomised controlled trial and quasi-experimental studies designs were included in the final analysis based on quality assessment by adopting the Down and Black checklist and finally pooled analysis was done by random effect model. This systematic review has been approved and registered by University of York. Results: A total of 16,570 published articles were accessed and finally 10 fulfilled our criteria that were analysed and interpreted. It demonstrated that the interventions has shown significantly increase vaccine coverage for childhood cluster diseases (OR 2.136 and p <0.05).Furthermore, it has been proved that an effect was more prominent for DTP (OR 2.397 and p<0.05) and measles (OR 2.628 and p<0.05), not as much for polio (OR 2.284 and p>0.05) and full vaccination schedule (OR 1.342 and p>0.05). Conclusions: Systematic review has concluded that the professional interventions are an effective while in improving the child immunisation coverage for cluster diseases in developing countries, major effect on DTP and measles. (author)

  6. Branched-chain amino acids enhance cyst development in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Yamamoto, Junya; Nishio, Saori; Hattanda, Fumihiko; Nakazawa, Daigo; Kimura, Toru; Sata, Michio; Makita, Minoru; Ishikawa, Yasunobu; Atsumi, Tatsuya

    2017-08-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The mammalian target of rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the drinking water to Pkd1 flox/flox :Mx1-Cre (cystic) mice from four to 22 weeks of age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at two weeks of age. The BCAA group showed significantly greater kidney/body weight ratio and higher cystic index in both the kidney and liver compared to the placebo-treated mice. We found that the L-type amino acid transporter 1 that facilitates BCAA entry into cells is strongly expressed in cells lining the cysts. We also found increased cyst-lining cell proliferation and upregulation of mTOR and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways in the BCAA group. In vitro, we cultured renal epithelial cell lines from Pkd1 null mice with or without leucine. Leucine was found to stimulate cell proliferation, as well as activate mTOR and MAPK/ERK pathways in these cells. Thus, BCAA accelerated disease progression by mTOR and MAPK/ERK pathways. Hence, BCAA may be harmful to patients with ADPKD. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  7. Incidental diagnosis of diseases on un-enhanced helical computed tomography performed for ureteric colic

    Directory of Open Access Journals (Sweden)

    Ather M Hammad

    2003-03-01

    Full Text Available Abstract Background Patients presenting in the emergency room with flank pain suggestive of acute ureteric colic may have alternative underlying conditions mimicking ureteric stones. An early diagnosis and appropriate treatment for other causes of flank pain is important. The majority of centers around the world are increasingly using un-enhanced helical CT (UHCT for evaluation of ureteric colic. This study was conducted to determine the incidence and spectrum of significant incidental diagnoses established or suggested on UHCT performed for suspected renal/ureteric colic. Methods Urologist and radiologist reviewed 233 consecutive UHCT, performed for suspected renal/ureteral colic along with assessment of the medical records. Radiological diagnoses of clinical entities not suspected otherwise were analyzed. All other relevant radiological, biochemical and serological investigations and per-operative findings were also noted. Results Ureteral calculi were identified in 148 examinations (64%, findings of recent passage of calculi in 10 (4% and no calculus in 75 examinations (32%. Overall the incidental findings (additional or alternative diagnosis were found in 28 (12% CT scans. Twenty (71% of these diagnoses were confirmed by per-operative findings, biopsy, and other radiological and biochemical investigations or on clinical follow up. Conclusion A wide spectrum of significant incidental diagnoses can be identified on UHCT performed for suspected renal/ureteral colic. In the present series of 233 consecutive CT examinations, the incidence of incidental diagnosis was 12%.

  8. MR mammography: influence of menstrual cycle on the dynamic contrast enhancement of fibrocystic disease

    International Nuclear Information System (INIS)

    Rieber, A.; Nuessle, K.; Merkle, E.; Tomczak, R.; Brambs, H.J.; Kreienberg, R.

    1999-01-01

    Magnetic resonance mammography (MRM) provides data regarding the nature of tumours based on contrast medium dynamics; fibrocystic changes in the breast, however, may lead to false-positive results. This study investigated whether the contrast medium dynamics of fibrocystic changes are dependent on the menstrual cycle. Twenty-four patients with palpable lumps but normal mammographies and ultrasound studies were examined. The MRM technique was performed during the first and second part of the menstrual cycle using a FLASH 3D sequence, both native and at 1, 2, 3 and 8 min after intravenous application of 0.15 mmol/kg body weight of gadodiamide. The calculated time-intensity curves were evaluated based on the following criteria: early percentage of contrast medium uptake in relation to the native value; formation of a plateau phenomenon after the second minute; the point of maximal contrast medium uptake; and calculation of the contrast enhancing index. During the second half of the menstrual cycle, a generally greater contrast medium uptake was observed. Nevertheless, when further diagnostic criteria, such as continuous contrast medium increase as a function of time, were considered, there was no increased rate of false-positive findings. The phase of the menstrual cycle may affect the specificity of the examination, if only the quantitative contrast medium uptake and the percentage of contrast medium uptake in the first 2 min are considered. A control MRM during the other half of the cycle may then be indicated and additional diagnostic criteria may improve specificity. (orig.)

  9. Prediction of presence of kidney disease in patients undergoing intravenous iodinated contrast enhanced computed tomography: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Schreuder, Sanne M.; Stoker, Jaap; Bipat, Shandra [University of Amsterdam, Department of Radiology, Academic Medical Centre, G1-212, Amsterdam (Netherlands)

    2017-04-15

    To validate two previously presented models containing risk factors to identify patients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m{sup 2} or eGFR <45 ml/min/1.73 m{sup 2}. In random patients undergoing intravenous contrast-enhanced computed tomography (CECT) the following risk factors were assessed: history of urological/nephrological disease, hypertension, diabetes mellitus, anaemia, congestive heart failure, other cardiovascular disease or multiple myeloma or Waldenstroem disease. Data on kidney function, age, gender and type and indication of CECT were also registered. We studied two models: model A - diabetes mellitus, history of urological/nephrological disease, cardiovascular disease, hypertension; model B - diabetes mellitus, history of urological/nephrological disease, age >75 years and congestive heart failure. For each model, associations with eGFR <60 ml/min/1.73 m{sup 2} or eGFR <45 ml/min/1.73 m{sup 2} was studied. A total of 1,001 patients, mean age 60.36 years were included. In total, 92 (9.2 %) patients had an eGFR <60 ml/min/1.73 m{sup 2} and 11 (1.1 %) patients an eGFR <45 ml/min/1.73 m{sup 2}. Model A detected 543 patients: 81 with eGFR <60 ml/min/1.73 m{sup 2} (missing 11) and all 11 with eGFR <45 ml/min/1.73 m{sup 2}. Model B detected 420 patients: 70 (missing 22) with eGFR <60 ml/min/1.73 m{sup 2} and all 11 with eGFR <45 ml/min/1.73 m{sup 2}. Associations were significant (p < 0.05). Model B resulted in the lowest superfluous eGFR measurements while detecting all patients with eGFR <45 ml/min/1.73 m{sup 2} and nearly all with eGFR <60 ml/min/1.73 m{sup 2}. (orig.)

  10. Enhanced Depth SD-OCT Images Reveal Characteristic Choroidal Changes in Patients With Vogt-Koyanagi-Harada Disease.

    Science.gov (United States)

    Li, Mei; Liu, Qiuhui; Luo, Yan; Li, Yonghao; Lin, Shaofen; Lian, Ping; Yang, Qiufen; Li, Xiaofang; Liu, Xialin; Sadda, SriniVas; Lu, Lin

    2016-11-01

    To identify characteristic choroidal changes of patients with Vogt-Koyanagi-Harada (VKH) disease at different stages. Fifty-four patients with VKH in the acute uveitic or convalescent stages, 24 patients with central serous chorioretinopathy (CSC), and 54 normal participants were enrolled in this prospective, observational study. Enhanced depth imaging spectral-domain optical coherence tomography scans were captured for all subjects to allow for comparison of choroidal morphological findings. Numerous round or oval hyperreflective profiles with hyporeflective cores, corresponding to choroidal vessels, were observed in the choroid of control participants and patients with CSC; whereas the numbers of these profiles were markedly decreased in the choroid of VKH patients in both the acute uveitic and convalescent stages. A reduction in vascular profiles in the choroid is observed in VKH and may aid in the differentiation with disorders such as CSC. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1004-1012.]. Copyright 2016, SLACK Incorporated.

  11. Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis

    International Nuclear Information System (INIS)

    Airaksinen, Antero; Pariente, Nonia; Menendez-Arias, Luis; Domingo, Esteban

    2003-01-01

    BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV) can be cured of virus by treatment with the antiviral nucleoside analogue ribavirin. To study whether the process involved an increase in the number of mutations in the mutant spectrum of the viral population, viral genomes were cloned from persistently infected cells treated or untreated with ribavirin. An increase of up to 10-fold in mutation frequencies associated with ribavirin treatment was observed in the viral genomes from the treated cultures as compared with parallel, untreated cultures. To address the possible mechanisms of enhanced mutagenesis, we investigated the mutagenic effects of ribavirin together with guanosine, and mycophenolic acid in the presence or absence of guanosine. Changes in the intracellular nucleotide concentrations were determined for all treatments. The results suggest that the increased mutation frequencies were not dependent on nucleotide pool imbalances or due to selection of preexisting genomes but they were produced by a mutagenic action of ribavirin

  12. MR mammography: influence of menstrual cycle on the dynamic contrast enhancement of fibrocystic disease

    Energy Technology Data Exchange (ETDEWEB)

    Rieber, A.; Nuessle, K.; Merkle, E.; Tomczak, R.; Brambs, H.J. [Ulm Univ. (Germany). Abt. Radiologie 1 (Roentgendiagnostik); Kreienberg, R. [Ulm Univ. (Germany). Dept. of Gynecology

    1999-08-01

    Magnetic resonance mammography (MRM) provides data regarding the nature of tumours based on contrast medium dynamics; fibrocystic changes in the breast, however, may lead to false-positive results. This study investigated whether the contrast medium dynamics of fibrocystic changes are dependent on the menstrual cycle. Twenty-four patients with palpable lumps but normal mammographies and ultrasound studies were examined. The MRM technique was performed during the first and second part of the menstrual cycle using a FLASH 3D sequence, both native and at 1, 2, 3 and 8 min after intravenous application of 0.15 mmol/kg body weight of gadodiamide. The calculated time-intensity curves were evaluated based on the following criteria: early percentage of contrast medium uptake in relation to the native value; formation of a plateau phenomenon after the second minute; the point of maximal contrast medium uptake; and calculation of the contrast enhancing index. During the second half of the menstrual cycle, a generally greater contrast medium uptake was observed. Nevertheless, when further diagnostic criteria, such as continuous contrast medium increase as a function of time, were considered, there was no increased rate of false-positive findings. The phase of the menstrual cycle may affect the specificity of the examination, if only the quantitative contrast medium uptake and the percentage of contrast medium uptake in the first 2 min are considered. A control MRM during the other half of the cycle may then be indicated and additional diagnostic criteria may improve specificity. (orig.) With 2 figs., 2 tabs., 24 refs.

  13. Diagnosis of gastro-oesophageal reflux disease is enhanced by adding oesophageal histology and excluding epigastric pain.

    Science.gov (United States)

    Vakil, N; Vieth, M; Wernersson, B; Wissmar, J; Dent, J

    2017-05-01

    The diagnosis of gastro-oesophageal reflux disease (GERD) in clinical practice is limited by the sensitivity and specificity of symptoms and diagnostic testing. To determine if adding histology as a criterion and excluding patients with epigastric pain enhances the diagnosis for GERD. Patients with frequent upper gastrointestinal symptoms who had not taken a proton pump inhibitor in the previous 2 months and who had evaluable distal oesophageal biopsies were included (Diamond study: NCT00291746). Epithelial hyperplasia was identified when total epithelial thickness was at least 430 μm. Investigation-based GERD criteria were: presence of erosive oesophagitis, pathological oesophageal acid exposure and/or positive symptom-acid association probability. Symptoms were assessed using the Reflux Disease Questionnaire and a pre-specified checklist. Overall, 127 (55%) of the 231 included patients met investigation-based GERD criteria and 195 (84%) met symptom-based criteria. Epithelial hyperplasia was present in 89 individuals, of whom 61 (69%) met investigation-based criteria and 83 (93%) met symptom-based criteria. Adding epithelial hyperplasia as a criterion increased the number of patients diagnosed with GERD on investigation by 28 [12%; number needed to diagnose (NND): 8], to 155 (67%). The proportion of patients with a symptom-based GERD diagnosis who met investigation-based criteria including epithelial hyperplasia was significantly greater when concomitant epigastric pain was absent than when it was present (P < 0.05; NND: 8). Histology increases diagnosis of GERD and should be performed when clinical suspicion is high and endoscopy is negative. Excluding patients with epigastric pain enhances sensitivity for the diagnosis of GERD. © 2017 John Wiley & Sons Ltd.

  14. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-06-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  15. Enhanced Prevalence of Plasmatic Soluble MHC Class I Chain-Related Molecule in Vascular Pregnancy Diseases

    Directory of Open Access Journals (Sweden)

    Jean Baptiste Haumonte

    2014-01-01

    Full Text Available The major histocompatibility complex class I related chain (MIC is a stress-inducible protein modulating the function of immune natural killer (NK cells, a major leukocyte subset involved in proper trophoblast invasion and spiral artery remodeling. Aim of the study was to evaluate whether upregulation of soluble MIC (sMIC may reflect immune disorders associated to vascular pregnancy diseases (VPD. sMIC was more frequently detected in the plasma of women with a diagnostic of VPD (32% than in normal term-matched pregnancies (1.6%, P<0.0001, with highest prevalence in intrauterine fetal death (IUDF, 44% and vascular intrauterine growth restriction (IUGR, 39%. sMIC levels were higher in preeclampsia (PE than in IUFD (P<0.01 and vascular IUGR (P<0.05. sMIC detection was associated with bilateral early diastolic uterine notches (P=0.037, thrombocytopenia (P=0.03, and high proteinuria (P=0.03 in PE and with the vascular etiology of IUGR (P=0.0038. Incubation of sMIC-positive PE plasma resulted in downregulation of NKG2D expression and NK cell-mediated IFN-γ production in vitro. Our work thus suggests that detection of sMIC molecule in maternal plasma may constitute a hallmark of altered maternal immune functions that contributes to vascular disorders that complicate pregnancy, notably by impairing NK-cell mediated production of IFN-γ, an essential cytokine favoring vascular modeling.

  16. Prophage induction is enhanced and required for renal disease and lethality in an EHEC mouse model.

    Directory of Open Access Journals (Sweden)

    Jessica S Tyler

    2013-03-01

    Full Text Available Enterohemorrhagic Escherichia coli (EHEC, particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2, the primary virulence factor expressed by EDL933 (an O157:H7 strain, is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2. Using the germ-free mouse, we show the essential role 933W induction plays in the virulence of EDL933 infection. An EDL933 derivative with a single mutation in its 933W prophage, resulting specifically in that phage being uninducible, colonizes the intestines, but fails to cause any of the pathological changes seen with the parent strain. Hence, induction of the 933W prophage is the primary event leading to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET, with a biosensor that specifically measures induction of the 933W prophage. Using this biosensor to measure 933W induction in germ-free mice, we found an increase three logs greater than was expected from in vitro results. Since the induced population produces and releases Stx2, this result indicates that an activity in the intestine increases Stx2 production.

  17. Cerebral blood flow mapping using stable xenon-enhanced CT in sickle cell cerebrovascular disease

    International Nuclear Information System (INIS)

    Numaguchi, Y.; Robinson, A.E.; Carey, J.E.

    1990-01-01

    The cerebral blood flow (CBF) of 25 patients with sickle cell cerebrovascular disease (SCCVD) was examined using a xenon-CT flow mapping method. Brain CT and MR findings were correlated with those of the xenon-CT flow studies. CBF defects on xenon-CT correlated reasonably well with the areas of cortical infarctions on the MR images, but in 27% of the cases, flow defects were slightly larger than the areas of infarctions on the MR images. In deep watershed or basal ganglia infarctions, abnormal CBF was noted about the cerebral cortex near infarctions in 72% of the patients, regardless of infarction sizes on the MR images. However, decreased CBF was recognized in 4 of the 9 children whose MR images were virtually normal. Thus, the extent of flow depletion cannot be predicted accurately by MR imaging alone. Xenon-CT flow mapping proved a safe and reliable procedure for evaluation of the CBF of patients with SCCVD. Although this study is preliminary, it may have a potential in selecting patients for hypertransfusion therapy, as a noninvasive test and for following children with SCCVD during their therapy. Careful correlation of results of CBF with those of MR imaging or of CT is important for objective interpretations of flow mapping images. (orig.)

  18. Fluorinated Chaperone-β-Cyclodextrin Formulations for β-Glucocerebrosidase Activity Enhancement in Neuronopathic Gaucher Disease.

    Science.gov (United States)

    García-Moreno, M Isabel; de la Mata, Mario; Sánchez-Fernández, Elena M; Benito, Juan M; Díaz-Quintana, Antonio; Fustero, Santos; Nanba, Eiji; Higaki, Katsumi; Sánchez-Alcázar, José A; García Fernández, José M; Ortiz Mellet, Carmen

    2017-03-09

    Amphiphilic glycomimetics encompassing a rigid, undistortable nortropane skeleton based on 1,6-anhydro-l-idonojirimycin and a polyfluorinated antenna, when formulated as the corresponding inclusion complexes with β-cyclodextrin (βCD), have been shown to behave as pharmacological chaperones (PCs) that efficiently rescue lysosomal β-glucocerebrosidase mutants associated with the neuronopathic variants of Gaucher disease (GD), including the highly refractory L444P/L444P and L444P/P415R single nucleotide polymorphs, in patient fibroblasts. The body of work here presented includes the design criteria for the PC prototype, the synthesis of a series of candidates, the characterization of the PC:βCD complexes, the determination of the selectivity profiles toward a panel of commercial and human lysosomal glycosidases, the evaluation of the chaperoning activity in type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (adult neuronopathic) GD fibroblasts, the confirmation of the rescuing mechanism by immunolabeling, and the analysis of the PC:GCase binding mode by docking experiments.

  19. Music as a Memory Enhancer in Patients with Alzheimer’s Disease

    Science.gov (United States)

    Simmons-Stern, Nicholas R.; Budson, Andrew E.; Ally, Brandon A.

    2010-01-01

    Musical mnemonics have a long and diverse history of popular use. In addition, music processing in general is often considered spared by the neurodegenerative effects of Alzheimer’s disease (AD). Research examining these two phenomena is limited, and no work to our knowledge has explored the effectiveness of musical mnemonics in AD. The present study sought to investigate the effect of music at encoding on the subsequent recognition of associated verbal information. Lyrics of unfamiliar children’s songs were presented bimodally at encoding, as visual stimuli accompanied by either a sung or a spoken recording. Patients with AD demonstrated better recognition accuracy for the sung lyrics than the spoken lyrics, while healthy older adults showed no significant difference between the two conditions. We propose two possible explanations for these findings: first, that the brain areas subserving music processing may be preferentially spared by AD, allowing a more holistic encoding that facilitates recognition, and second, that music heightens arousal in patients with AD, allowing better attention and improved memory. PMID:20452365

  20. Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.

    Science.gov (United States)

    Kulshreshtha, Parul; Tiwari, Ashutosh; Priyanka; Joon, Shikha; Sinha, Subrata; Bhatnagar, Rakesh

    2015-12-01

    Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. Copyright © 2015. Published by Elsevier Ltd.

  1. Enhanced Store-Operated Calcium Entry in Platelets is Associated with Peripheral Artery Disease in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Weijie Xia

    2015-11-01

    Full Text Available Background/Aims: Platelet dysfunction plays an important role in thrombosis in diabetes with peripheral artery disease (PAD. Store-operated calcium entry (SOCE and stromal interaction molecule 1 (STIM1 regulate platelet activity by modulating calcium influx. We hypothesized that enhanced SOCE in platelets is associated with diabetes with PAD. Methods: We studied the activity of platelets from healthy participants and from type 2 diabetic patients. Platelet calcium influx and protein expression of STIM1 and sarcoendoplasmic reticulum Ca2+-ATPase 3 (SERCA3 were investigated. Results: Compared with platelets from diabetic patients without PAD, platelets from diabetic patients with PAD exhibited significantly increased SOCE . Menthol administration completely inhibited calcium influx in platelets from diabetic patients without PAD, but this effect was blunted in those from diabetic patients with PAD. Furthermore, the increase in SOCE was correlated with the ankle brachial index (ABI in diabetic patients. High glucose significantly up-regulated STIM1 and SERCA3 protein expression and induced the phosphorylation of phospholipase C (PLC in platelets from healthy participants. This effect was attenuated in the presence of menthol or U73122, an inhibitor of PLC. Similarly, significant increases in STIM1 and SERCA3 protein expression were found in platelets from diabetic patients compared to those from healthy participants. Conclusion: Platelets from diabetic patients with PAD exhibited enhanced Store-operated calcium influx, which was associated with elevated STIM1/SERCA3 expression via a PLC-dependent pathway and was inhibited by menthol.

  2. Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.

    Science.gov (United States)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Youri; Kwon, Young-Man; Kang, Sang-Moo

    2017-11-01

    Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia. Copyright © 2017. Published by Elsevier Inc.

  3. Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

    Science.gov (United States)

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan

    2014-10-17

    This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

  4. Distinct neural systems underlying reduced emotional enhancement for positive and negative stimuli in early Alzheimer's disease.

    Science.gov (United States)

    Mistridis, Panagiota; Taylor, Kirsten I; Kissler, Johanna M; Monsch, Andreas U; Kressig, Reto W; Kivisaari, Sasa L

    2013-01-01

    Emotional information is typically better remembered than neutral content, and previous studies suggest that this effect is subserved particularly by the amygdala together with its interactions with the hippocampus. However, it is not known whether amygdala damage affects emotional memory performance at immediate and delayed recall, and whether its involvement is modulated by stimulus valence. Moreover, it is unclear to what extent more distributed neocortical regions involved in e.g., autobiographical memory, also contribute to emotional processing. We investigated these questions in a group of patients with Alzheimer's disease (AD), which affects the amygdala, hippocampus and neocortical regions. Healthy controls (n = 14), patients with AD (n = 15) and its putative prodrome amnestic mild cognitive impairment (n = 11) completed a memory task consisting of immediate and delayed free recall of a list of positive, negative and neutral words. Memory performance was related to brain integrity in region of interest and whole-brain voxel-based morphometry analyses. In the brain-behavioral analyses, the left amygdala volume predicted the immediate recall of both positive and negative material, whereas at delay, left and right amygdala volumes were associated with performance with positive and negative words, respectively. Whole-brain analyses revealed additional associations between left angular gyrus integrity and the immediate recall of positive words as well as between the orbitofrontal cortex and the delayed recall of negative words. These results indicate that emotional memory impairments in AD may be underpinned by damage to regions implicated in emotional processing as well as frontoparietal regions, which may exert their influence via autobiographical memories and organizational strategies.

  5. Use of Mobile Device Accelerometry to Enhance Evaluation of Postural Instability in Parkinson Disease.

    Science.gov (United States)

    Ozinga, Sarah J; Linder, Susan M; Alberts, Jay L

    2017-04-01

    To determine the accuracy of inertial measurement unit data from a mobile device using the mobile device relative to posturography to quantify postural stability in individuals with Parkinson disease (PD). Criterion standard. Motor control laboratory at a clinic. A sample (N=28) of individuals with mild to moderate PD (n=14) and age-matched community-dwelling individuals without PD (n=14) completed the study. Not applicable. Center of mass (COM) acceleration measures were compared between the mobile device and the NeuroCom force platform to determine the accuracy of mobile device measurements during performance of the Sensory Organization Test (SOT). Analyses examined test-retest reliability of both systems and sensitivity of (1) the equilibrium score from the SOT and (2) COM acceleration measures from the force platform and mobile device to quantify postural stability across populations. Metrics of COM acceleration from inertial measurement unit data and the NeuroCom force platform were significantly correlated across balance conditions and groups (Pearson r range, .35 to .97). The SOT equilibrium scores failed to discriminate individuals with and without PD. However, the multiplanar measures of COM acceleration from the mobile device exhibited good to excellent reliability across SOT conditions and were able to discriminate individuals with and without PD in conditions with the greatest balance demands. Metrics employing medial-lateral movement produce a more sensitive outcome than the equilibrium score in identifying postural instability associated with PD. Overall, the output from the mobile device provides an accurate and reliable method of rapidly quantifying balance in individuals with PD. The portable and affordable nature of a mobile device with the application makes it ideally suited to use biomechanical data to aid in clinical decision making. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  6. Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Roshni Srivastava

    2015-10-01

    Full Text Available Mutations in Wnt-signaling coreceptor LRP6 have been linked to coronary artery disease (CAD by unknown mechanisms. Here, we show that reduced LRP6 activity in LRP6R611C mice promotes loss of vascular smooth muscle cell (VSMC differentiation, leading to aortic medial hyperplasia. Carotid injury augmented these effects and led to partial to total vascular obstruction. LRP6R611C mice on high-fat diet displayed dramatic obstructive CAD and exhibited an accelerated atherosclerotic burden on LDLR knockout background. Mechanistically, impaired LRP6 activity leads to enhanced non-canonical Wnt signaling, culminating in diminished TCF7L2 and increased Sp1-dependent activation of PDGF signaling. Wnt3a administration to LRP6R611C mice improved LRP6 activity, led to TCF7L2-dependent VSMC differentiation, and rescued post-carotid-injury neointima formation. These findings demonstrate the critical role of intact Wnt signaling in the vessel wall, establish a causal link between impaired LRP6/TCF7L2 activities and arterial disease, and identify Wnt signaling as a therapeutic target against CAD.

  7. When Art Meets Gardens: Does It Enhance the Benefits? The Nancy Hypothesis of Care for Persons with Alzheimer's Disease.

    Science.gov (United States)

    Jonveaux, Thérèse Rivasseau; Fescharek, Reinhard

    2018-01-01

    The creation of healing gardens for persons with Alzheimer's disease and related diseases (ADRD) offers vast potential. They can play a role in the scaffolding of cognitive disorders, emotional stress, sensory processing, sense of harmony, and appeasement. These effects are achieved through a distributed interplay of psychological functions with the immediate environment and local culture on the one hand, and dialogue on the other. The garden, a natural canvas created by man, shares with art the ability to foster an esthetic sense for which the perception can be measured by functional neurological imaging exploration. Art represents a mediator for the collaborative realization of distributed psychological functions between different individuals. Based on the hypothesis of an optimization of the therapeutic potential of a garden by a design adapted to the neuro-psycho-social and cultural specificities of its users combined with the thoughtful introduction of an artistic dimension, the "art, memory and life" healing garden was created at the University Hospital of Nancy as a prototype for persons with ADRD. The design concept was based on two hypotheses that we formulate herein, discuss their theoretical foundation, and suggest enhanced design for therapeutic gardens based upon our experience.

  8. An enhanced voxel-based morphometry method to investigate structural changes: application to Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xingfeng; Messe, Arnaud; Marrelec, Guillaume; Pelegrini-Issac, Melanie [UPMC Univ Paris 06, Laboratoire d' Imagerie Fonctionnelle, and LINeM, GHU Pitie-Salpetriere, Inserm, Paris, Cedex 13 (France); Universite de Montreal, LINeM, International Laboratory of Neuroimaging and Modeling, IUGM, Montreal (Canada); Universite de Montreal, CRM, Montreal (Canada); Benali, Habib [UPMC Univ Paris 06, Laboratoire d' Imagerie Fonctionnelle, and LINeM, GHU Pitie-Salpetriere, Inserm, Paris, Cedex 13 (France); Universite de Montreal, LINeM, International Laboratory of Neuroimaging and Modeling, IUGM, Montreal (Canada); Universite de Montreal, CRM, Montreal (Canada); CHU Pitie-Salpetriere, UMR Inserm/UPMC, Laboratoire d' Imagerie Fonctionnelle, Faculte de Medecine, Paris Cedex 13 (France)

    2010-03-15

    When characterizing regional cerebral gray matter differences in structural magnetic resonance images (sMRI) by voxel-based morphometry (VBM), one faces a known drawback of VBM, namely that histogram unequalization in the intensity images introduces false-positive results. To overcome this limitation, we propose to improve VBM by a new approach (called eVBM for enhanced VBM) that takes the histogram distribution of the sMRI into account by adding a histogram equalization step within the VBM procedure. Combining this technique with two most widely used VBM software packages (FSL and SPM), we studied GM variability in a group of 62 patients with Alzheimer's disease compared to 73 age-matched elderly controls. The results show that eVBM can reduce the number of false-positive differences in gray matter concentration. Because it takes advantage of the properties of VBM while improving sMRI histogram distribution at the same time, the proposed method is a powerful approach for analyzing gray matter differences in sMRI and may be of value in the investigation of sMRI gray and white matter abnormalities in a variety of brain diseases. (orig.)

  9. Assessment of dynamic contrast enhancement of the small bowel in active Crohn's disease using 3D MR enterography

    International Nuclear Information System (INIS)

    Knuesel, Patrick R.; Kubik, Rahel A.; Crook, David W.; Eigenmann, Franz; Froehlich, Johannes M.

    2010-01-01

    Purpose: To retrospectively compare the dynamic contrast enhancement of the small bowel segments with and without active Crohn's disease at 3D MR enterography (MRE). Materials and methods: Thirteen patients (five men, eight women; mean age 41.2 years; range 29-56) were imaged on a 1.5-T MR scanner (Sonata, Siemens Medical) with standard MR sequences after having ingested 1000 ml of a 3% mannitol solution. Subsequently, high resolution 3D gradient-echo (volumetric interpolated breath-hold examination = VIBE) data sets were obtained pre-contrast and 20-40 s, 60-80 s, and 120-140 s after i.v. Gd-DOTA administration (0.2 mmol/kg). Signal enhancement was measured on single slices both in normal and histologically confirmed (12/13) inflamed small bowel wall segments as well as in the aorta, the psoas muscle, and the background to calculate signal-to-noise (SNR) and contrast-to-noise ratios (CNR). Results: Small bowel wall enhancement was significantly higher (p < 0.05) in inflamed compared to normal segments at 20-40 s (SNR inflamed: 58.7 ± 33.8 vs normal: 36.0 ± 19.8; p = 0.048; CNR inflamed: 34.8 ± 23.4 vs normal: 16.3 ± 11.2; p = 0.017) and at 60-80 s (SNR: 60.3 ± 25.1 vs 41.9 ± 20.0; p = 0.049; CNR: 34.9 ± 15.1 vs 19.3 ± 13.2; p = 0.01) after i.v. contrast administration, respectively. Even at 120-140 s CNR was still increased in inflamed segments (33.7 ± 16.0 vs 18.1 ± 13.2; p = 0.04), while differences in SNR did not attain statistical significance (63.0 ± 26.2 vs 45.3 ± 23.3; p = 0.15). Conclusion: In active Crohn's disease, histologically confirmed inflamed small bowel wall segments demonstrate a significantly increased early uptake of gadolinium on 3D VIBE sequences compared to normal small bowel segments.

  10. Evaluating the use of mobile phone technology to enhance cardiovascular disease screening by community health workers.

    Science.gov (United States)

    Surka, Sam; Edirippulige, Sisira; Steyn, Krisela; Gaziano, Thomas; Puoane, Thandi; Levitt, Naomi

    2014-09-01

    Primary prevention of cardiovascular disease (CVD),by identifying individuals at risk is a well-established, but costly strategy when based on measurements that depend on laboratory analyses. A non-laboratory, paper-based CVD risk assessment chart tool has previously been developed to make screening more affordable in developing countries. Task shifting to community health workers (CHWs) is being investigated to further scale CVD risk screening. This study aimed to develop a mobile phone CVD risk assessment application and to evaluate its impact on CHW training and the duration of screening for CVD in the community by CHWs. A feature phone application was developed using the open source online platform, CommCare(©). CHWs (n=24) were trained to use both paper-based and mobile phone CVD risk assessment tools. They were randomly allocated to using one of the risk tools to screen 10-20 community members and then crossed over to screen the same number, using the alternate risk tool. The impact on CHW training time, screening time and margin of error in calculating risk scores was recorded. A focus group discussion evaluated experiences of CHWs using the two tools. The training time was 12.3h for the paper-based chart tool and 3h for the mobile phone application. 537 people were screened. The mean screening time was 36 min (SD=12.6) using the paper-base chart tool and 21 min (SD=8.71) using the mobile phone application, p=mobile phone calculations were correct. Qualitative findings from the focus group discussion corresponded with the findings of the pilot study. The reduction in CHW training time, CVD risk screening time, lack of errors in calculation of a CVD risk score and end user satisfaction when using a mobile phone application, has implications in terms of adoption and sustainability of this primary prevention strategy to identify people with high CVD risk who can be referred for appropriate diagnoses and treatment. Copyright © 2014 Elsevier Ireland Ltd. All

  11. Interleukin-1β Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    You Yin

    Full Text Available Sleep alleviates Alzheimer's disease (AD-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL-1β and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1β and APOEε4 SNPs using ligase detection reaction (LDR technology. Blood levels of IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α were measured using ELISA after lipopolysaccharide (LPS stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI, and activities of daily living (ADL. Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015. Compared to the IL-1β CC genotype (-31, the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010. AD patients carrying the APOEε4 allele and the IL-1β TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1β levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1β-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1β-31TT genotype and homozygous APOEε4 combined

  12. What are the benefits of cognitive enhancers for Alzheimer's Disease: use of Population Impact Measures

    Directory of Open Access Journals (Sweden)

    Heller Richard F

    2007-11-01

    Full Text Available Abstract Background The study aims to quantify the population impact of prescribing cholinesterase inhibitors to slow the cognitive decline in Alzheimer's disease (AD, and to compare with the benefit of treating hypertension to prevent the onset of AD. Methods Literature review to ascertain the prevalence of AD, benefits of interventions, analysis of local and national surveys to measure the current use of interventions in the relevant population and application of the relevant findings to calculate Population Impact Measures. The Number of Events Prevented in a Population (NEPP by the intervention over a defined time period is calculated for a UK urban population in one Local Authority (population size 217,000. Results Treatment of all eligible patients with mild to moderate AD with Cholinesterase Inhibitors would prevent cognitive deterioration (measured by ADAS – cog scale in 123.6 (95% Confidence Intervals (CI 82.3, 169.1, 16.4 (95% CI 2.1, 31.2 would show a mild improvement (4 points or more on the ADAS – cog scale and 2.6 (95% CI 0.2, 5.8 would show an improvement of 7 points or more over a period of 6 months. This would require the treatment of 406 patients with Cholinesterase Inhibitors. Increasing from the current treatment rate of 46% of eligible patients to 'best practice' level would prevent cognitive deterioration in 66.8 (95% CI 44.0, 92.6, 8.99 (95% CI 1.2, 16.8 and 1.4 (95% CI 0.11, 3.2 would improve by 4 and 7 points respectively on the ADAS – cog scale over 6 months. This would require the treatment of an extra 187 patients with Cholinesterase Inhibitors beyond current practice, at an additional annual direct drug cost of £187,000. Improving the treatment of hypertension from current practice by 20% could prevent 8.2 (95% CI 2.3, 16.8 incident cases of AD in the next year. This would require the treatment of an extra 2711 patients with antihypertensive drugs. Conclusion Population Impact Measures are a new method to

  13. Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.

    Science.gov (United States)

    Schaeffer, Evelin L; Forlenza, Orestes V; Gattaz, Wagner F

    2009-01-01

    Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease. The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects. MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest. Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury. The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.

  14. Real-time monitoring of school absenteeism to enhance disease surveillance: a pilot study of a mobile electronic reporting system.

    Science.gov (United States)

    Lawpoolsri, Saranath; Khamsiriwatchara, Amnat; Liulark, Wongwat; Taweeseneepitch, Komchaluch; Sangvichean, Aumnuyphan; Thongprarong, Wiraporn; Kaewkungwal, Jaranit; Singhasivanon, Pratap

    2014-05-12

    School absenteeism is a common source of data used in syndromic surveillance, which can eventually be used for early outbreak detection. However, the absenteeism reporting system in most schools, especially in developing countries, relies on a paper-based method that limits its use for disease surveillance or outbreak detection. The objective of this study was to develop an electronic real-time reporting system on school absenteeism for syndromic surveillance. An electronic (Web-based) school absenteeism reporting system was developed to embed it within the normal routine process of absenteeism reporting. This electronic system allowed teachers to update students' attendance status via mobile tablets. The data from all classes and schools were then automatically sent to a centralized database for further analysis and presentation, and for monitoring temporal and spatial patterns of absent students. In addition, the system also had a disease investigation module, which provided a link between absenteeism data from schools and local health centers, to investigate causes of fever among sick students. The electronic school absenteeism reporting system was implemented in 7 primary schools in Bangkok, Thailand, with total participation of approximately 5000 students. During May-October 2012 (first semester), the percentage of absentees varied between 1% and 10%. The peak of school absenteeism (sick leave) was observed between July and September 2012, which coincided with the peak of dengue cases in children aged 6-12 years being reported to the disease surveillance system. The timeliness of a reporting system is a critical function in any surveillance system. Web-based application and mobile technology can potentially enhance the use of school absenteeism data for syndromic surveillance and outbreak detection. This study presents the factors that determine the implementation success of this reporting system.

  15. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

    2011-09-22

    The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host

  16. Malignant pleural disease: diagnosis by using diffusion-weighted and dynamic contrast-enhanced MR imaging--initial experience.

    Science.gov (United States)

    Coolen, Johan; De Keyzer, Frederik; Nafteux, Philippe; De Wever, Walter; Dooms, Christophe; Vansteenkiste, Johan; Roebben, Ilse; Verbeken, Eric; De Leyn, Paul; Van Raemdonck, Dirk; Nackaerts, Kristiaan; Dymarkowski, Steven; Verschakelen, Johny

    2012-06-01

    To investigate the use of diffusion-weighted (DW) imaging for differentiating benign lesions from malignant pleural disease (MPD) and to retrospectively assess dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging acquisitions to find out whether combining these measurements with DW imaging could improve the diagnostic value of DW imaging. This study was approved by the local ethics committee, and all patients provided written informed consent. Thirty-one consecutive patients with pleural abnormalities suspicious for MPD underwent whole-body positron emission tomography (PET)/computed tomography (CT) and thorax MR examinations. Diagnostic thoracoscopy with histopathologic analysis of pleural biopsies served as the reference standard. First-line evaluation of each suspicious lesion was performed by using the apparent diffusion coefficient (ADC) calculated from the DW image, and the optimal cutoff value was found by using receiver operating characteristic curve analysis. Afterward, DCE MR imaging data were used to improve the diagnosis in the range of ADCs where DW imaging results were equivocal. Sensitivity, specificity, and accuracy of PET/CT for diagnosis of MPD were 100%, 35.3%, and 64.5%. The optimal ADC threshold to differentiate benign lesions from MPD with DW MR imaging was 1.52 × 10(-3) mm(2)/sec, with sensitivity, specificity, and accuracy of 71.4%, 100%, and 87.1%, respectively. This result could be improved to 92.8%, 94.1%, and 93.5%, respectively, when DCE MR imaging data were included in those cases where ADC was between 1.52 and 2.00 × 10(-3) mm(2)/sec. A total of 20 patients had disease diagnosed correctly, nine had disease diagnosed incorrectly, and two cases were undetermined with PET/CT. DW imaging helped stage disease correctly in 27 patients and incorrectly in four. The undetermined cases at PET/CT were correctly diagnosed at MR imaging. DW imaging is a promising tool for differentiating MPD from benign lesions, with high

  17. Dynamic gadolinium-enhanced subtraction MR imaging - a simple technique for the early diagnosis of Legg-Calve-Perthes disease: preliminary results

    International Nuclear Information System (INIS)

    Sebag, G.; Ducou Le Pointe, H.; Klein, I.; Maiza, D.; Mazda, K.; Bensahel, H.; Hassan, M.

    1997-01-01

    To determine whether the simple technique of dynamic gadolinium-enhanced subtraction MR imaging, which is available on standard MR units, can detect ischemia of the femoral head in children with early Legg-Calve-Perthes disease (LCP). Bone perfusion of eight hips in four patients (mean age 7.5 years) was studied using dynamic gadolinium-enhanced substraction MR imaging at the onset of proven LCP (with initial negative plain films). Enhancement of subtracted images was compared with that on standard MR images and with bone scintigraphy findings. Subtraction MR imaging depicted ischemia as a widespread absence of enhancement and was in good agreement with bone scintigraphy. The subtraction technique improved the sensitivity and the specificity of MR imaging in two children. Furthermore, subtraction MR imaging allowed recognition of the pattern of early reperfusion. Our preliminary results indicate that dynamic gadolinium-enhanced subtraction MRI is a simple and promising means of early recognition of ischemia in LCP. (orig.)

  18. Enhancing health policymakers' information literacy knowledge and skill for policymaking on control of infectious diseases of poverty in Nigeria.

    Science.gov (United States)

    Uneke, Chigozie Jesse; Ezeoha, Abel Ebeh; Uro-Chukwu, Henry; Ezeonu, Chinonyelum Thecla; Ogbu, Ogbonnaya; Onwe, Friday; Edoga, Chima

    2015-01-01

    In Nigeria, one of the major challenges associated with evidence-to-policy link in the control of infectious diseases of poverty (IDP), is deficient information literacy knowledge and skill among policymakers. There is need for policymakers to acquire the skill to discover relevant information, accurately evaluate retrieved information and to apply it correctly. To use information literacy tool of International Network for Availability of Scientific Publications (INASP) to enhance policymakers' knowledge and skill for policymaking on control of IDP in Nigeria. Modified "before and after" intervention study design was used in which outcomes were measured on target participants both before the intervention is implemented and after. This study was conducted in Ebonyi State, south-eastern Nigeria and participants were career health policy makers. A two-day health-policy information literacy training workshop was organized to enhance participants" information literacy capacity. Topics covered included: introduction to information literacy; defining information problem; searching for information online; evaluating information; science information; knowledge sharing interviews; and training skills. A total of 52 policymakers attended the workshop. The pre-workshop mean rating (MNR) of knowledge and capacity for information literacy ranged from 2.15-2.97, while the post-workshop MNR ranged from 3.34-3.64 on 4-point scale. The percentage increase in MNR of knowledge and capacity at the end of the workshop ranged from 22.6%-55.3%. The results of this study suggest that through information literacy training workshop policy makers can acquire the knowledge and skill to identify, capture and share the right kind of information in the right contexts to influence relevant action or a policy decision.

  19. Dietary supplementation with Cynodon dactylon (L.) enhances innate immunity and disease resistance of Indian major carp, Catla catla (Ham.).

    Science.gov (United States)

    Kaleeswaran, B; Ilavenil, S; Ravikumar, S

    2011-12-01

    Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P < 0.05) enhanced most of the non-specific immune parameters tested. Among the experimental diet groups, significantly increased response of non-specific immunity was seen in group III (5%). Disease resistant analysis against Aeromonas hydrophila was performed in control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative percent survival rate (RPS) was observed in treated samples, which is directly proportional to concentration of the extract. Additionally, electron microscopic studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the experimental diet groups than the control. All these experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. T135I substitution in the nonstructural protein 2C enhances foot-and-mouth disease virus replication.

    Science.gov (United States)

    Yuan, Tiangang; Wang, Haiwei; Li, Chen; Yang, Decheng; Zhou, Guohui; Yu, Li

    2017-12-01

    The foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays an important role in viral replication, virulence, and host range. It has been shown that deletions of 10 or 19-20 amino acids in the C-terminal half of 3A attenuate serotype O and C FMDVs, which replicate poorly in bovine cells but normally in porcine-derived cells, and the C-terminal half of 3A is not essential for serotype Asia1 FMDV replication in BHK-21 cells. In this study, we constructed a 3A deletion FMDV mutant based on a serotype O FMDV, the wild-type virus O/YS/CHA/05, with a 60-amino acid deletion in the 3A protein sequence, between residues 84 and 143. The rescued virus O/YS/CHA/05-Δ3A exhibited slower growth kinetics and formed smaller plaques compared to O/YS/CHA/05 in both BHK-21 and IBRS-2 cells, indicating that the 60-amino acid deletion in the 3A protein impaired FMDV replication. After 14 passages in BHK-21 cells, the replication capacity of the passaged virus O/YS/CHA/05-Δ3A-P14 returned to a level similar to the wild-type virus, suggesting that amino acid substitutions responsible for the enhanced replication capacity occurred in the genome of O/YS/CHA/05-Δ3A-P14. By sequence analysis, two amino acid substitutions, P153L in VP1 and T135I in 2C, were found in the O/YS/CHA/05-Δ3A-P14 genome compared to the O/YS/CHA/05-Δ3A genome. Subsequently, the amino acid substitutions VP1 P153L and 2C T135I were separately introduced into O/YS/CHA/05-Δ3A to rescue mutant viruses for examining their growth kinetics. Results showed that the 2C T135I instead of the VP1 P153L enhanced the virus replication capacity. The 2C T135I substitution also improved the replication of the wild-type virus, indicating that the effect of 2C T135I substitution on FMDV replication is not associated with the 3A deletion. Furthermore, our results showed that the T135I substitution in the nonstructural protein 2C enhanced O/YS/CHA/05 replication through promoting viral RNA synthesis.

  1. Evaluation of radiation dose in chest scan with enhanced dual-source computed tomography in children with congenital heart disease

    International Nuclear Information System (INIS)

    Hou Zhihui; Lu Bin; Tang Xiang; Han Lei

    2011-01-01

    Objective: To evaluate the radiation dose from enhanced dual-source computed Tomography (DSCT) scan on children with congenital heart disease (CHD). Methods: Seventy children with CHD, age from 1 month to 8 years old, were scanned with enhanced DSCT. Children were divided by age into 5 years old group. The differences among three groups were tested by F test. Then, the SNK test was used to compare the difference between each group. Multiple linear regression analysis was used to test the relationship of dose length product (DLP) with the age, weight, voltage, current, pitch and scan sheet. Results: The average value of DLP was (144.46± 74.07) mGy·cm for all the 70 cases, and that of effective does (ED) was (4.68±2.34) mSv. There were significant differences of DLP among the 3 groups [ 5 years (208.00±73.87) mGy · cm, F=8.26, P=0.0009]. The SNK test showed statistical differences of DLP between 5 years old group (q=5.21, 6.52, P=0.009, 0.004). The difference of DLP between 1-5 years old group and > 5 years old group did not reach significant (q=0.28, P=0.48). The differences of ED was not statistically significant among the three groups [ 5 years (3.74±1.33) mSv, F=0.54, P=0.59]. DLP was positively correlated with age (4.3 years, r=0.54186, P=0.0008), weight (12.1 kg, r=0.56371, P=0.0004), voltage [(95.48±6.99) kV, r=0.63269, P<0.01], current [(138.55±40.67) mA, r=0.79608, P< 0.0001] and scan sheet (236.10±46.51, r=0.72192, P<0.01). DLP was negative correlated with pitch (0.48±0.03, r=-0.46693, P=0.0047). Conclusion: Higher DLP was observed in children over 1 year old under enhanced DSCT scan, but ED was not statistically significant among the three groups due to the higher K value in the children under 1 year old. (authors)

  2. Enhancement pattern of small hepatocellular carcinoma (HCC) at contrast-enhanced US (CEUS), MDCT, and MRI: Intermodality agreement and comparison of diagnostic sensitivity between 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines

    International Nuclear Information System (INIS)

    Furlan, Alessandro; Marin, Daniele; Cabassa, Paolo; Taibbi, Adele; Brunelli, Elena; Agnello, Francesco; Lagalla, Roberto; Brancatelli, Giuseppe

    2012-01-01

    Objective: To evaluate agreement between contrast-enhanced ultrasound (CEUS), multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) for the assessment of typical and atypical enhancement patterns of small hepatocellular carcinoma (HCC); and to compare diagnostic sensitivity of 2005 and 2010 American Association for the Study of Liver Diseases (AASLD) guidelines. Materials and methods: Between January 2008 and December 2009, we included cirrhotic patients with newly diagnosed 10–20 mm HCC imaged at two contrast-enhanced imaging techniques among CEUS, MDCT, and MRI. Dynamic studies were reviewed by two radiologists to assess enhancement pattern. Percentage of cases with concordant findings and Cohen coefficient (k) were calculated. McNemar's test was used to compare sensitivity between 2005 and 2010 AASLD guidelines. Results: There were 91 patients (69 M; 22 F; mean age, 68 years) with 96 HCCs, studied with a combination of CEUS and MDCT (n = 59), CEUS and MRI (n = 26), or MDCT and MRI (n = 11). Intermodality agreement for assessment of tumor enhancement pattern was 67% (k = 0.294, P = 0.001). Typical enhancement pattern was detected coincidentally at two imaging modalities in 50 (52%) HCCs. Sensitivity for the diagnosis of HCC increased significantly using the 2010 AASLD (81/96 (84%) vs. 50/96 (52%), P < 0.001). Conclusions: Agreement between two imaging modalities for the detection of typical tumor enhancement pattern was reached in 52% of cases. The 2010 AASLD guidelines significantly increased the sensitivity for the diagnosis of HCC

  3. Application of glycerol as a foliar spray activates the defence response and enhances disease resistance of Theobroma cacao.

    Science.gov (United States)

    Zhang, Yufan; Smith, Philip; Maximova, Siela N; Guiltinan, Mark J

    2015-01-01

    Previous work has implicated glycerol-3-phosphate (G3P) as a mobile inducer of systemic immunity in plants. We tested the hypothesis that the exogenous application of glycerol as a foliar spray might enhance the disease resistance of Theobroma cacao through the modulation of endogenous G3P levels. We found that exogenous application of glycerol to cacao leaves over a period of 4 days increased the endogenous level of G3P and decreased the level of oleic acid (18:1). Reactive oxygen species (ROS) were produced (a marker of defence activation) and the expression of many pathogenesis-related genes was induced. Notably, the effects of glycerol application on G3P and 18:1 fatty acid content, and gene expression levels, in cacao leaves were dosage dependent. A 100 mm glycerol spray application was sufficient to stimulate the defence response without causing any observable damage, and resulted in a significantly decreased lesion formation by the cacao pathogen Phytophthora capsici; however, a 500 mm glycerol treatment led to chlorosis and cell death. The effects of glycerol treatment on the level of 18:1 and ROS were constrained to the locally treated leaves without affecting distal tissues. The mechanism of the glycerol-mediated defence response in cacao and its potential use as part of a sustainable farming system are discussed. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  4. Comparison of acetazolamide-enhanced brain SPECT using Tc-99m ECD with cerebral angiography in patients with cerebrovascular disease

    International Nuclear Information System (INIS)

    Choi, Y. Y.; Moon, D. H.; Ryu, J. S.; Yang, S. H.; Lee, H. K.; Lee, J. H.; Kim, J. S.; Kim, K. A.

    1997-01-01

    Cerebral vascular reserve can be assessed by development of collateral channels (DCC) on cerebral angiography(CA) or vasoreactivity (VR) on acetazolamide-enhanced brain SPECT (ACZ-SPECT). The purpose of this study was to compare Tc-99m ECD ACZ-SPECT with CA in the evaluation of vascular reserve in patients (pts) with cerebrovascular disease(CVD). Twenty seven patients with CVD, including TIA (n=13), infarction (n=11) and asymptomatic pts (AS, n=3), underwent CA and ACZ-SPECT. Basal and ACZ-SPECT was obtained consecutively, and image subtraction was performed. On CA, degree of DCC was scored 0-3 (0: normal, 3: poor) according to parenchymal staining on delayed film. In ACZ-SPECT, decrease of VR was graded 0-3 (0: normal, 3: more than 30% decrease). The correlation between degree of stenosis, DCC and VR were analyzed. 1) Variable degree of VR or DCC was observed in totally occluded or stenotic cerebral arterial territories. 2) In arterial territories with poor DCC, ACZ-SPECT showed poor VR. However, in 5 out of 11 TIA or AS with good DCC, poor VR was observed. These data suggests that 1) cerebral hemodynamic status cannot be assessed by the degree of stenosis on CA alone. 2) DCC may overestimate the cerebral vascular reserve in patients with TIA or AS. 3) ACZ-SPECT plays a complementary role to CA for evaluation of cerebral hemodynamic status in pts with CVD

  5. Differential Diagnosis of Parkinson Disease, Essential Tremor, and Enhanced Physiological Tremor with the Tremor Analysis of EMG

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2017-01-01

    Full Text Available We investigate the differential diagnostic value of tremor analysis of EMG on Parkinson’s disease (PD, essential tremor (ET, and enhanced physiological tremor (EPT. Clinical data from 25 patients with PD, 20 patients with ET, and 20 patients with EPT were collected. The tremor frequency and muscle contraction pattern of the resting, posture, and 500 g and 1000 g overload were recorded. The frequency of PD tremor was 4–6 Hz, and the frequency of ET was also in this range; the frequency of EPT is 6–12 hz having some overlap with PD. The muscle contraction patterns of the ET and EPT group were mainly synchronous contraction, and the muscle contraction mode of the PD group was mainly alternating contraction. Having tremor latency from rest to postural position and having changes in tremor amplitude after mental concentration in PD might distinguish ET. Tremor analysis of EMG was able to distinguish PD from ET and EPT by varying the tremor frequency and muscle contraction pattern. It can also differentiate between PD and ET by the latency and concentration effect and ET and EPT by weight load effect.

  6. Flexible Spectral Imaging Color Enhancement and Probe-based Confocal Laser Endomicroscopy in Minimal Change Esophageal Reflux Disease.

    Science.gov (United States)

    Pittayanon, Rapat; Aumkaew, Surasak; Rerknimitr, Rungsun; Wisedopas, Naruemon; Kullavanijaya, Pinit

    2016-07-25

    Although flexible spectral imaging color enhancement (FICE) can facilitate the diagnosis of minimal change esophageal reflux disease (MERD), the complicated diagnostic criteria cause suboptimal inter-observer agreement. Confocal laser endomicroscopy (CLE) yields good diagnostic results but its inter-observer agreement has never been explored. This study compares the diagnostic value of magnifying FICE and probe-based CLE (pCLE) for MERD and evaluates the inter-observer agreement of both techniques. Thirty-six patients with suspected MERD and 18 asymptomatic controls were recruited. Magnifying FICE was used for evaluation of distal esophagus. pCLE counted the number of intrapapillary capillary loops (IPCLs) using more than five IPCLs in 500×500 micron area as a criterion for MERD diagnosis. The validity scores and interobserever agreement of both FICE and pCLE were assessed. For FICE vs. pCLE, the accuracy was 79% vs. 87%, sensitivity 94% vs. 97%, specificity 50% vs. 66%, positive predictive value 79% vs. 85%, and negative predictive value 82% vs. 92%. Interobserver agreement of FICE was fair to substantial, whereas pCLE had substantial to almost perfect agreement. Both FICE and pCLE have good operating characteristics and can facilitate the MERD diagnosis. However, among different observers, pCLE is more consistent on MERD diagnosis.

  7. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    Directory of Open Access Journals (Sweden)

    Zongli eHu

    2015-01-01

    Full Text Available Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi technology to partially silence three different genes (FOW2, FRP1 and OPR in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  8. Dynamic contrast-enhanced ultrasound and transient arterial occlusion for quantification of arterial perfusion reserve in peripheral arterial disease

    International Nuclear Information System (INIS)

    Amarteifio, E.; Wormsbecher, S.; Krix, M.; Demirel, S.; Braun, S.; Delorme, S.; Böckler, D.; Kauczor, H.-U.; Weber, M.-A.

    2012-01-01

    Objective: To quantify muscular micro-perfusion and arterial perfusion reserve in peripheral arterial disease (PAD) with dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion. Materials and methods: This study had local institutional review board approval and written informed consent was obtained from all subjects. We examined the dominant lower leg of 40 PAD Fontaine stage IIb patients (mean age, 65 years) and 40 healthy volunteers (mean age, 54 years) with CEUS (7 MHz; MI, 0.28) during continuous intravenous infusion of 4.8 mL microbubbles. Transient arterial occlusion at mid-thigh level simulated physical exercise. With time–CEUS–intensity curves obtained from regions of interest within calf muscles, we derived the maximum CEUS signal after occlusion (max) and its time (t max ), slope to maximum (m), vascular response after occlusion (AUC post ), and analysed accuracy, receiver operating characteristic (ROC) curves, and correlations with ankle-brachial index (ABI) and walking distance. Results: All parameters differed in PAD and volunteers (p max was delayed (31.2 ± 13.6 vs. 16.7 ± 8.5 s, p post as optimal parameter combination for diagnosing PAD and therefore impaired arterial perfusion reserve. Conclusions: Dynamic CEUS with transient arterial occlusion quantifies muscular micro-perfusion and arterial perfusion reserve. The technique is accurate to diagnose PAD.

  9. Viral-toxin interactions and Parkinson’s disease: poly(I:C priming enhanced the neurodegenerative effects of paraquat

    Directory of Open Access Journals (Sweden)

    Bobyn Jessica

    2012-05-01

    Full Text Available Abstract Background Parkinson’s disease (PD has been linked with exposure to a variety of environmental and immunological insults (for example, infectious pathogens in which inflammatory and oxidative processes seem to be involved. In particular, epidemiological studies have found that pesticide exposure and infections may be linked with the incidence of PD. The present study sought to determine whether exposure to a viral mimic prior to exposure to pesticides would exacerbate PD-like pathology. Methods Mice received a supra-nigral infusion of 5 μg of the double-stranded RNA viral analog, polyinosinic: polycytidylic acid (poly(I:C, followed 2, 7 or 14 days later by administration of the pesticide, paraquat (nine 10 mg/kg injections over three weeks. Results As hypothesized, poly(I:C pre-treatment enhanced dopamine (DA neuron loss in the substantia nigra pars compacta elicited by subsequent paraquat treatment. The augmented neuronal loss was accompanied by robust signs of microglial activation, and by increased expression of the catalytic subunit (gp91 of the NADPH oxidase oxidative stress enzyme. However, the paraquat and poly(I:C treatments did not appreciably affect home-cage activity, striatal DA terminals, or subventricular neurogenesis. Conclusions These findings suggest that viral agents can sensitize microglial-dependent inflammatory responses, thereby rendering nigral DA neurons vulnerable to further environmental toxin exposure.

  10. The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease.

    Science.gov (United States)

    Singbrant, Sofie; Wall, Meaghan; Moody, Jennifer; Karlsson, Göran; Chalk, Alistair M; Liddicoat, Brian; Russell, Megan R; Walkley, Carl R; Karlsson, Stefan

    2014-04-01

    The proto-oncogene SKI is highly expressed in human myeloid leukemia and also in murine hematopoietic stem cells. However, its operative relevance in these cells remains elusive. We have over-expressed SKI to define its intrinsic role in hematopoiesis and myeloid neoplasms, which resulted in a robust competitive advantage upon transplantation, a complete dominance of the stem and progenitor compartments, and a marked enhancement of myeloid differentiation at the expense of other lineages. Accordingly, enforced expression of SKI induced a gene signature associated with hematopoietic stem cells and myeloid differentiation, as well as hepatocyte growth factor signaling. Here we demonstrate that, in contrast to what has generally been assumed, the significant impact of SKI on hematopoiesis is independent of its ability to inhibit TGF-beta signaling. Instead, myeloid progenitors expressing SKI are partially dependent on functional hepatocyte growth factor signaling. Collectively our results demonstrate that SKI is an important regulator of hematopoietic stem cell activity and its overexpression leads to myeloproliferative disease.

  11. Propolis and Herba Epimedii extracts enhance the non-specific immune response and disease resistance of Chinese sucker, Myxocyprinus asiaticus.

    Science.gov (United States)

    Zhang, Guobin; Gong, Shiyuan; Yu, Denghang; Yuan, Hanwen

    2009-03-01

    The effect of traditional Chinese medicine (TCM) formulated from propolis and Herba Epimedii extracts at the ratio of 3:1 (w/w) on non-specific immune response of Chinese sucker (Myxocyprinus asiaticus) was investigated. Fish were fed diets containing 0 (control), 0.1%, 0.5% or 1.0% TCM extracts for five weeks. The respiratory burst and phagocytic activities of blood leukocytes, lysozyme and natural haemolytic complement activities in plasma were measured weekly. After five weeks of feeding, fish were infected with Aeromonas hydrophila and mortalities were recorded. Results of this study showed that feeding Chinese sucker with different dosage of TCM extracts stimulated respiratory burst activity, phagocytosis of phagocytic cells in blood and lysozyme activity in plasma. They had no effect on plasma natural haemolytic complement activity. All dosage of treated groups showed reduced mortality following A. hydrophila infection. Feed containing 0.5% TCM extracts was the most effective with the mortality of the fish significantly reduced by 35% compared to the control. The results indicate that propolis and Herba Epimedii extracts in combination enhances the non-specific immune response and disease resistance of Chinese sucker against A. hydrophila.

  12. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    Science.gov (United States)

    Hu, Zongli; Parekh, Urvi; Maruta, Natsumi; Trusov, Yuri; Botella, Jimmy

    2015-01-01

    Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi) technology to partially silence three different genes (FOW2, FRP1 and OPR) in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  13. ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation

    Directory of Open Access Journals (Sweden)

    Tina Zimmermann

    2016-10-01

    Full Text Available Huntington's disease (HD is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor. By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA chemical and two genetic HD mouse models (R6/2 and N171-82Q on the basis of distinct behavioral parameters, including CatWalk gait analysis. Explicit rescue of motor function by BDNF neural progenitors was found in QA-lesioned mice, whereas genetic mouse models displayed only minor improvements. Tumor formation was absent, and regeneration was attributed to enhanced neuronal and striatal differentiation. In addition, adult neurogenesis was preserved in a BDNF-dependent manner. Our findings provide significant insight for establishing therapeutic strategies for HD to ameliorate neurodegenerative symptoms.

  14. Compute raided classification of ventilation patterns inpatients with chronic obstructive pulmonary diseases at two-phase xenon-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Son Ho; Goo, Jin Mo; Lee, Chang Hyun; Lee, You Kyung; Jin, Kwang Nam; Choo, Ji Yung; Lee, Nyoung Keun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Julip; Hong, Helen [Dept. of Multimedia Engineering, Seoul Women' s University, Seoul (Korea, Republic of)

    2014-06-15

    To evaluate the technical feasibility, performance, and interobserver agreement of a computer-aided classification (CAC) system for regional ventilation at two-phase xenon-enhanced CT in patients with chronic obstructive pulmonary disease (COPD). Thirty-eight patients with COPD underwent two-phase xenon ventilation CT with resulting wash-in (WI) and wash-out (WO) xenon images. The regional ventilation in structural abnormalities was visually categorized into four patterns by consensus of two experienced radiologists who compared the xenon attenuation of structural abnormalities with that of adjacent normal parenchyma in the WI and WO images, and it served as the reference. Two series of image datasets of structural abnormalities were randomly extracted for optimization and validation. The proportion of agreement on a per-lesion basis and receiver operating characteristics on a per-pixel basis between CAC and reference were analyzed for optimization. Thereafter, six readers independently categorized the regional ventilation in structural abnormalities in the validation set without and with a CAC map. Interobserver agreement was also compared between assessments without and with CAC maps using multirater κ statistics. Computer-aided classification maps were successfully generated in 31 patients (81.5%). The proportion of agreement and the average area under the curve of optimized CAC maps were 94% (75/80) and 0.994, respectively. Multirater k value was improved from moderate (k=0.59: 95% confidence interval [CI], 0.56-0.62) at the initial assessment to excellent with the CAC map.

  15. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Pei Xuan Lee

    2016-06-01

    Full Text Available Dengue virus (DENV causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  16. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  17. Comparison of Xenon-Enhanced Area-Detector CT and Krypton Ventilation SPECT/CT for Assessment of Pulmonary Functional Loss and Disease Severity in Smokers.

    Science.gov (United States)

    Ohno, Yoshiharu; Fujisawa, Yasuko; Takenaka, Daisuke; Kaminaga, Shigeo; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

    2018-02-01

    The objective of this study was to compare the capability of xenon-enhanced area-detector CT (ADCT) performed with a subtraction technique and coregistered 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity in smokers. Forty-six consecutive smokers (32 men and 14 women; mean age, 67.0 years) underwent prospective unenhanced and xenon-enhanced ADCT, 81m Kr-ventilation SPECT/CT, and pulmonary function tests. Disease severity was evaluated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. CT-based functional lung volume (FLV), the percentage of wall area to total airway area (WA%), and ventilated FLV on xenon-enhanced ADCT and SPECT/CT were calculated for each smoker. All indexes were correlated with percentage of forced expiratory volume in 1 second (%FEV 1 ) using step-wise regression analyses, and univariate and multivariate logistic regression analyses were performed. In addition, the diagnostic accuracy of the proposed model was compared with that of each radiologic index by means of McNemar analysis. Multivariate logistic regression showed that %FEV 1 was significantly affected (r = 0.77, r 2 = 0.59) by two factors: the first factor, ventilated FLV on xenon-enhanced ADCT (p < 0.0001); and the second factor, WA% (p = 0.004). Univariate logistic regression analyses indicated that all indexes significantly affected GOLD classification (p < 0.05). Multivariate logistic regression analyses revealed that ventilated FLV on xenon-enhanced ADCT and CT-based FLV significantly influenced GOLD classification (p < 0.0001). The diagnostic accuracy of the proposed model was significantly higher than that of ventilated FLV on SPECT/CT (p = 0.03) and WA% (p = 0.008). Xenon-enhanced ADCT is more effective than 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity.

  18. A multi nutrient concept to enhance synapse formation and function: science behind a medical food for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Sijben John W.C.

    2011-09-01

    Full Text Available Alzheimer’s Disease (AD is the leading cause of dementia. Epidemiological studies suggest that AD is linked with poor status of nutrients including DHA, B-vitamins and the vitamins E and C. Ongoing neurodegeneration, particularly synaptic loss, leads to the classical clinical features of AD namely, memory impairment, language deterioration, and executive and visuospatial dysfunction. The main constituents of neural and synaptic membranes are phospholipids. Supplemenation of animals with three dietary precursors of phospholipids namely, DHA, uridine monophosphate and choline, results in increased levels of brain phospholipids, synaptic proteins, neurite outgrowth, dendritic spines formation (i.e. the anatomical precursors of new synapses and an improvement in learning and memory. Other nutrients act as co-factors in the synthesis pathway of neuronal membranes. For example B-vitamins are involved in methylation processes, thereby enhancing the availability of choline as a synaptic membrane precursor. A multi-nutrient concept that includes these nutrients may improve membrane integrity, thereby influencing membrane-dependent processes such as receptor function and amyloid precursor protein (APP processing, as shown by reduced amyloid production and amyloid β plaque burden, as well as toxicity. Together, these insights provided the basis for the development of a medical food for patients with AD, Souvenaid®, containing a specific combination of nutrients (Fortasyn™ Connect and designed to enhance synapse formation in AD. The effect of Souvenaid on memory and cognitive performance was recently assessed in a proof-of-concept study, SOUVENIR I, with 212 drug-naïve mild AD patients (MMSE 20-26. This proof-of-concept study demonstrated that oral nutritional supplementation with Souvenaid® for 12 weeks improves memory in patients with mild AD. To confirm and extend these findings, we have designed and initiated three additional studies. Two of

  19. Improved Mitochondrial Function in Brain Aging and Alzheimer Disease – the New Mechanism of Action of the Old Metabolic Enhancer Piracetam

    Science.gov (United States)

    Leuner, Kristina; Kurz, Christopher; Guidetti, Giorgio; Orgogozo, Jean-Marc; Müller, Walter E.

    2010-01-01

    Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g., might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, this new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions. PMID:20877425

  20. Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model.

    Science.gov (United States)

    Wu, Jun; Ryskamp, Daniel A; Liang, Xia; Egorova, Polina; Zakharova, Olga; Hung, Gene; Bezprozvanny, Ilya

    2016-01-06

    In Huntington's disease (HD), mutant Huntingtin (mHtt) protein causes striatal neuron dysfunction, synaptic loss, and eventual neurodegeneration. To understand the mechanisms responsible for synaptic loss in HD, we developed a corticostriatal coculture model that features age-dependent dendritic spine loss in striatal medium spiny neurons (MSNs) from YAC128 transgenic HD mice. Age-dependent spine loss was also observed in vivo in YAC128 MSNs. To understand the causes of spine loss in YAC128 MSNs, we performed a series of mechanistic studies. We previously discovered that mHtt protein binds to type 1 inositol (1,4,5)-trisphosphate receptor (InsP3R1) and increases its sensitivity to activation by InsP3. We now report that the resulting increase in steady-state InsP3R1 activity reduces endoplasmic reticulum (ER) Ca(2+) levels. Depletion of ER Ca(2+) leads to overactivation of the neuronal store-operated Ca(2+) entry (nSOC) pathway in YAC128 MSN spines. The synaptic nSOC pathway is controlled by the ER resident protein STIM2. We discovered that STIM2 expression is elevated in aged YAC128 striatal cultures and in YAC128 mouse striatum. Knock-down of InsP3R1 expression by antisense oligonucleotides or knock-down or knock-out of STIM2 resulted in normalization of nSOC and rescue of spine loss in YAC128 MSNs. The selective nSOC inhibitor EVP4593 was identified in our previous studies. We now demonstrate that EVP4593 reduces synaptic nSOC and rescues spine loss in YAC128 MSNs. Intraventricular delivery of EVP4593 in YAC128 mice rescued age-dependent striatal spine loss in vivo. Our results suggest EVP4593 and other inhibitors of the STIM2-dependent nSOC pathway as promising leads for HD therapeutic development. In Huntington's disease (HD) mutant Huntingtin (mHtt) causes early corticostriatal synaptic dysfunction and eventual neurodegeneration of medium spine neurons (MSNs) through poorly understood mechanisms. We report here that corticostriatal cocultures prepared from

  1. Anti-colitis and -adhesion effects of daikenchuto via endogenous adrenomedullin enhancement in Crohn's disease mouse model.

    Science.gov (United States)

    Kono, Toru; Kaneko, Atsushi; Hira, Yoshiki; Suzuki, Tatsuya; Chisato, Naoyuki; Ohtake, Nobuhiro; Miura, Naoko; Watanabe, Tsuyoshi

    2010-06-01

    Adrenomedullin (ADM) is a member of the calcitonin family of regulatory peptides, and is reported to have anti-inflammatory effects in animal models of Crohn's disease (CD). We investigated the therapeutic effects of daikenchuto (DKT), an extracted Japanese herbal medicine, on the regulation of endogenous ADM in the gastrointestinal tract in a CD mouse model. Colitis was induced in mice by intrarectal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS); afterwards, DKT was given orally. Colonic damage was assessed on day 3 by macroscopic and microscopic observation, enzyme immunoassays of proinflammatory cytokines in the colonic mucosa, and serum amyloid A (SAA), a hepatic acute-phase protein. To determine the involvement of ADM, an ADM antagonist was instilled intrarectally before DKT administration. The effect of DKT on ADM production by intestinal epithelial cells was evaluated by enzyme immunoassay and real-time PCR. DKT significantly attenuated mucosal damage and colonic inflammatory adhesions, and inhibited elevations of SAA in plasma and the proinflammatory cytokines TNFα and IFNγ in the colon. Small and large intestinal epithelial cells produced higher levels of ADM after DKT stimulation. A DKT-treated IEC-6 cell line also showed enhanced ADM production at protein and mRNA levels. Abolition of this effect by pretreatment with an ADM antagonist shows that DKT appears to exert its anti-colitis effect via up-regulation of endogenous ADM in the intestinal tract. DKT exerts beneficial effects in a CD mouse model through endogenous release and production of ADM. Endogenous ADM may be a therapeutic target for CD. Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  2. Assessment of myocardial infarction with delayed-enhancement MRI in coronary artery disease: a correlative study with cardiac events

    International Nuclear Information System (INIS)

    Zhao Xinxiang; Yang Chao; Yang Dakuan; Yuan Shuguang; Yang Xinhuan; Wang Zhong

    2011-01-01

    Objective: To investigate the correlation between recent cardiac events and the score of myocardial infarction by delayed-enhancement MRI (DE-MRI). Methods: DE-MRI was performed in 40 subjects with coronary artery disease. The score of myocardial infarction by DE-MRI, the ejection fraction (EF) by echocardiography, recent cardiac events (the number of weekly nitroglycerin, the number of weekly angina episodes and the onset number of heart failure in the last year), 6-minute walking distance, as well as the Seattle angina questionnaire (SAQ) score were assessed. The Spearman correlation test and Kruskal-Wallis test, Mann-Whitney test were used for the statistics. Results: There were negative correlation between the myocardial infarction score by DE-MRI (median 12, inter-quartile range: 6.0-19.8) and the 6-minute walking distance (378.93±100.53), SAQ score (74.55±11.40) (r was 0.66 and 0.54, P< 0.05). The myocardial infarction score by DE-MRI was strongly correlated with the number of weekly nitroglycerin (median 1; inter-quartile range: 0-2.8), the number of weekly angina episodes (median 3, inter-quartile range: 1-6.5) and the onset number of heart failure in the last year (median 0, inter-quartile range: 0-2) (r was 0.87, 0.85 and 0.89, P<0.05). EF [(49.2±13.72)%] was negative correlation with the number of weekly nitroglycerin, the number of weekly angina episodes and the onset number of heart failure in the last year (r were 0.67, 0.73 and 0.73, P<0.05). Conclusion: DE-MRI can be used for evaluation and prediction of future cardiac events. (authors)

  3. Polyethylene glycol and contrast-enhanced MRI of Crohn's disease in children: preliminary experience

    Energy Technology Data Exchange (ETDEWEB)

    Magnano, Gianmichele; Granata, Claudio; Magnaguagno, Francesca; Rossi, Umberto; Toma, Paolo [Service of Radiology, Giannina Gaslini Hospital, Genoa (Italy); Barabino, Arrigo [Department of Gastroenterology, Giannina Gaslini Hospital, Genoa (Italy); Calevo, Maria Grazia [Service of Epidemiology and Biostatistics, Giannina Gaslini Hospital, Genoa (Italy)

    2003-06-01

    To assess the ability of MRI to detect bowel abnormalities in children affected by Crohn's disease (CD). We studied 22 children (age range 8-18 years) referred to us with a known history of CD. MRI was carried out using a 1.5-T unit with a maximum gradient field strength of 16 mT and a phased-array body coil. The sequences performed were breath-hold coronal and axial T2-weighted, express fat saturation, followed by T1-weighted, spoiled gradient, fast fat saturation after IV injection of gadolinium chelate (0.3 mmol/kg) for contrast enhancement of the bowel wall. Bowel distension was achieved using oral administration of isosmotic polyethylene glycol solution. Ileo-colonoscopy was considered the gold standard for evaluation of superficial abnormalities and stenoses of the colon and terminal ileum. MRI findings of bowel-wall thickening, increased vascularisation and extramural involvement were compared with the findings using B-mode and Doppler US. Concordance between MRI and endoscopy, B-mode US and Doppler US findings was determined by the Kappa statistical method. Superficial lesions were not shown by MRI. MR enteroclysis easily detected stenoses, thickening and hyperaemia of bowel wall. Concordance of findings between MRI and endoscopy was 90% (K=0.79, substantial concordance). Concordance of findings between MRI and US concerning bowel-wall thickening and increased vascularisation was 95% (K=0.875, excellent concordance) and 80% (K=0.6, fairly good concordance), respectively. Our initial results show that MRI can detect intra- and extra-mural lesions of CD. The high concordance observed between MRI, endoscopy, US and Doppler US findings suggests that MRI is at least comparable for diagnostic capability with these techniques offering, thanks to multiplanar projections, an improved visualisation of the bowel without ionising radiation. (orig.)

  4. Transcranial Direct Current Stimulation to Enhance Dual-Task Gait Training in Parkinson's Disease: A Pilot RCT.

    Science.gov (United States)

    Schabrun, Siobhan M; Lamont, Robyn M; Brauer, Sandra G

    2016-01-01

    To investigate the feasibility and safety of a combined anodal transcranial direct current stimulation (tDCS) and dual task gait training intervention in people with Parkinson's Disease (PD) and to provide data to support a sample size calculation for a fully powered trial should trends of effectiveness be present. A pilot, randomized, double-blind, sham-controlled parallel group trial with 12 week follow-up. A university physiotherapy department. Sixteen participants diagnosed with PD received nine dual task gait training sessions over 3 weeks. Participants were randomized to receive either active or sham tDCS applied for the first 20 minutes of each session. The primary outcome was gait speed while undertaking concurrent cognitive tasks (word lists, counting, conversation). Secondary measures included step length, cadence, Timed Up and Go, bradykinesia and motor speed. Gait speed, step length and cadence improved in both groups, under all dual task conditions. This effect was maintained at follow-up. There was no difference between the active and sham tDCS groups. Time taken to perform the TUGwords also improved, with no difference between groups. The active tDCS group did however increase their correct cognitive response rate during the TUGwords and TUGcount. Bradykinesia improved after training in both groups. Three weeks of dual task gait training resulted in improved gait under dual task conditions, and bradykinesia, immediately following training and at 12 weeks follow-up. The only parameter enhanced by tDCS was the number of correct responses while performing the dual task TUG. tDCS applied to M1 may not be an effective adjunct to dual task gait training in PD. Australia-New Zealand Clinical Trials Registry ACTRN12613001093774.

  5. Quantitative pre-clinical screening of therapeutics for joint diseases using contrast enhanced micro-computed tomography.

    Science.gov (United States)

    Willett, N J; Thote, T; Hart, M; Moran, S; Guldberg, R E; Kamath, R V

    2016-09-01

    The development of effective therapies for cartilage protection has been limited by a lack of efficient quantitative cartilage imaging modalities in pre-clinical in vivo models. Our objectives were two-fold: first, to validate a new contrast-enhanced 3D imaging analysis technique, equilibrium partitioning of an ionic contrast agent-micro computed tomography (EPIC-μCT), in a rat medial meniscal transection (MMT) osteoarthritis (OA) model; and second, to quantitatively assess the sensitivity of EPIC-μCT to detect the effects of matrix metalloproteinase inhibitor (MMPi) therapy on cartilage degeneration. Rats underwent MMT surgery and tissues were harvested at 1, 2, and 3 weeks post-surgery or rats received an MMPi or vehicle treatment and tissues harvested 3 weeks post-surgery. Parameters of disease progression were evaluated using histopathology and EPIC-μCT. Correlations and power analyses were performed to compare the techniques. EPIC-μCT was shown to provide simultaneous 3D quantification of multiple parameters, including cartilage degeneration and osteophyte formation. In MMT animals treated with MMPi, OA progression was attenuated, as measured by 3D parameters such as lesion volume and osteophyte size. A post-hoc power analysis showed that 3D parameters for EPIC-μCT were more sensitive than 2D parameters requiring fewer animals to detect a therapeutic effect of MMPi. 2D parameters were comparable between EPIC-μCT and histopathology. This study demonstrated that EPIC-μCT has high sensitivity to provide 3D structural and compositional measurements of cartilage and bone in the joint. EPIC-μCT can be used in combination with histology to provide a comprehensive analysis to screen new potential therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects

    Directory of Open Access Journals (Sweden)

    Kamil Brzóska

    2014-09-01

    Full Text Available [b]Introduction and objective[/b]. Chronic obstructive pulmonary disease (COPD is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer. [b]Materials and methods[/b]. We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases ([i]MMP1, MMP2, MMP3, MMP9, MMP12[/i] as well as tissue inhibitor of metalloproteinases ([i]TIMP1[/i] in two groups of subjects: COPD patients (54 subjects and COPD patients diagnosed for lung cancer occurrence (53 subjects.The levels of the respective proteins in blood serum were also analyzed. [b]Results[/b]. The frequencies of 2 genotypes, [i]MMP3[/i] rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in[i] MMPs[/i] blood levels between the studied groups. In addition, no genotype-associated differences in [i]TIMP1[/i] or[i] MMPs[/i] blood levels were observed. [b]Conclusions[/b]. Homozygocity for [i]MMP3[/i] rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.

  7. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  8. Newly Diagnosed Breast Cancer: Comparison of Contrast-enhanced Spectral Mammography and Breast MR Imaging in the Evaluation of Extent of Disease.

    Science.gov (United States)

    Lee-Felker, Stephanie A; Tekchandani, Leena; Thomas, Mariam; Gupta, Esha; Andrews-Tang, Denise; Roth, Antoinette; Sayre, James; Rahbar, Guita

    2017-11-01

    Purpose To compare the diagnostic performances of contrast material-enhanced spectral mammography and breast magnetic resonance (MR) imaging in the detection of index and secondary cancers in women with newly diagnosed breast cancer by using histologic or imaging follow-up as the standard of reference. Materials and Methods This institutional review board-approved, HIPAA-compliant, retrospective study included 52 women who underwent breast MR imaging and contrast-enhanced spectral mammography for newly diagnosed unilateral breast cancer between March 2014 and October 2015. Of those 52 patients, 46 were referred for contrast-enhanced spectral mammography and targeted ultrasonography because they had additional suspicious lesions at MR imaging. In six of the 52 patients, breast cancer had been diagnosed at an outside institution. These patients were referred for contrast-enhanced spectral mammography and targeted US as part of diagnostic imaging. Images from contrast-enhanced spectral mammography were analyzed by two fellowship-trained breast imagers with 2.5 years of experience with contrast-enhanced spectral mammography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for both imaging modalities and compared by using the Bennett statistic. Results Fifty-two women with 120 breast lesions were included for analysis (mean age, 50 years; range, 29-73 years). Contrast-enhanced spectral mammography had similar sensitivity to MR imaging (94% [66 of 70 lesions] vs 99% [69 of 70 lesions]), a significantly higher PPV than MR imaging (93% [66 of 71 lesions] vs 60% [69 of 115 lesions]), and fewer false-positive findings than MR imaging (five vs 45) (P contrast-enhanced spectral mammography depicted 11 of the 11 secondary cancers (100%) and MR imaging depicted 10 (91%). Conclusion Contrast-enhanced spectral mammography is potentially as sensitive as MR imaging in the evaluation of extent of disease in newly diagnosed

  9. Reproducibility of rest and exercise stress contrast-enhanced calf perfusion magnetic resonance imaging in peripheral arterial disease

    Directory of Open Access Journals (Sweden)

    Jiji Ronny S

    2013-01-01

    Full Text Available Abstract Background The purpose was to determine the reproducibility and utility of rest, exercise, and perfusion reserve (PR measures by contrast-enhanced (CE calf perfusion magnetic resonance imaging (MRI of the calf in normal subjects (NL and patients with peripheral arterial disease (PAD. Methods Eleven PAD patients with claudication (ankle-brachial index 0.67 ±0.14 and 16 age-matched NL underwent symptom-limited CE-MRI using a pedal ergometer. Tissue perfusion and arterial input were measured at rest and peak exercise after injection of 0.1 mM/kg of gadolinium-diethylnetriamine pentaacetic acid (Gd-DTPA. Tissue function (TF and arterial input function (AIF measurements were made from the slope of time-intensity curves in muscle and artery, respectively, and normalized to proton density signal to correct for coil inhomogeneity. Perfusion index (PI = TF/AIF. Perfusion reserve (PR = exercise TF/ rest TF. Intraclass correlation coefficient (ICC was calculated from 11 NL and 10 PAD with repeated MRI on a different day. Results Resting TF was low in NL and PAD (mean ± SD 0.25 ± 0.18 vs 0.35 ± 0.71, p = 0.59 but reproducible (ICC 0.76. Exercise TF was higher in NL than PAD (5.5 ± 3.2 vs. 3.4 ± 1.6, p = 0.04. Perfusion reserve was similar between groups and highly variable (28.6 ± 19.8 vs. 42.6 ± 41.0, p = 0.26. Exercise TF and PI were reproducible measures (ICC 0.63 and 0.60, respectively. Conclusion Although rest measures are reproducible, they are quite low, do not distinguish NL from PAD, and lead to variability in perfusion reserve measures. Exercise TF and PI are the most reproducible MRI perfusion measures in PAD for use in clinical trials.

  10. Expression of a novel antimicrobial peptide Penaeidin4-1 in creeping bentgrass (Agrostis stolonifera L. enhances plant fungal disease resistance.

    Directory of Open Access Journals (Sweden)

    Man Zhou

    Full Text Available BACKGROUND: Turfgrass species are agriculturally and economically important perennial crops. Turfgrass species are highly susceptible to a wide range of fungal pathogens. Dollar spot and brown patch, two important diseases caused by fungal pathogens Sclerotinia homoecarpa and Rhizoctonia solani, respectively, are among the most severe turfgrass diseases. Currently, turf fungal disease control mainly relies on fungicide treatments, which raises many concerns for human health and the environment. Antimicrobial peptides found in various organisms play an important role in innate immune response. METHODOLOGY/PRINCIPAL FINDINGS: The antimicrobial peptide - Penaeidin4-1 (Pen4-1 from the shrimp, Litopenaeus setiferus has been reported to possess in vitro antifungal and antibacterial activities against various economically important fungal and bacterial pathogens. In this study, we have studied the feasibility of using this novel peptide for engineering enhanced disease resistance into creeping bentgrass plants (Agrostis stolonifera L., cv. Penn A-4. Two DNA constructs were prepared containing either the coding sequence of a single peptide, Pen4-1 or the DNA sequence coding for the transit signal peptide of the secreted tobacco AP24 protein translationally fused to the Pen4-1 coding sequence. A maize ubiquitin promoter was used in both constructs to drive gene expression. Transgenic turfgrass plants containing different DNA constructs were generated by Agrobacterium-mediated transformation and analyzed for transgene insertion and expression. In replicated in vitro and in vivo experiments under controlled environments, transgenic plants exhibited significantly enhanced resistance to dollar spot and brown patch, the two major fungal diseases in turfgrass. The targeting of Pen4-1 to endoplasmic reticulum by the transit peptide of AP24 protein did not significantly impact disease resistance in transgenic plants. CONCLUSION/SIGNIFICANCE: Our results

  11. Overexpression of a modified plant thionin enhances disease resistance to citrus canker and huanglongbing (HLB, citrus greening)

    Science.gov (United States)

    Huanglongbing (HLB or citrus greening disease) caused by Candidatus Liberibacter asiaticus (Las) is a great threat to the United States citrus industry. Citrus canker is also an economically important disease associated with a bacterial pathogen (Xanthomonas citri). In this study, we characterized e...

  12. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression

    NARCIS (Netherlands)

    Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J.; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

    2015-01-01

    The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation.

  13. Estimating the arterial input function from dynamic contrast-enhanced MRI data with compensation for flow enhancement (II): Applications in spine diagnostics and assessment of crohn's disease.

    Science.gov (United States)

    van Schie, Jeroen J N; Lavini, Cristina; van Vliet, Lucas J; Kramer, Gem; Pieters-van den Bos, Indra; Marcus, J T; Stoker, Jaap; Vos, Frans M

    2018-05-01

    Pharmacokinetic (PK) models can describe microvascular density and integrity. An essential component of PK models is the arterial input function (AIF) representing the time-dependent concentration of contrast agent (CA) in the blood plasma supplied to a tissue. To evaluate a novel method for subject-specific AIF estimation that takes inflow effects into account. Retrospective study. Thirteen clinical patients referred for spine-related complaints; 21 patients from a study into luminal Crohn's disease with known Crohn's Disease Endoscopic Index of Severity (CDEIS). Dynamic fast spoiled gradient echo (FSPGR) at 3T. A population-averaged AIF, AIFs derived from distally placed regions of interest (ROIs), and the new AIF method were applied. Tofts' PK model parameters (including v p and K trans ) obtained with the three AIFs were compared. In the Crohn's patients K trans was correlated to CDEIS. The median values of the PK model parameters from the three methods were compared using a Mann-Whitney U-test. The associated variances were statistically assessed by the Brown-Forsythe test. Spearman's rank correlation coefficient was computed to test the correlation of K trans to CDEIS. The median v p was significantly larger when using the distal ROI approach, compared to the two other methods (P < 0.05 for both comparisons, in both applications). Also, the variances in v p were significantly larger with the ROI approach (P < 0.05 for all comparisons). In the Crohn's disease study, the estimated K trans parameter correlated better with the CDEIS (r = 0.733, P < 0.001) when the proposed AIF was used, compared to AIFs from the distal ROI method (r = 0.429, P = 0.067) or the population-averaged AIF (r = 0.567, P = 0.011). The proposed method yielded realistic PK model parameters and improved the correlation of the K trans parameter with CDEIS, compared to existing approaches. 3 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2018;47:1197-1204. © 2017

  14. Dynamic contrast-enhanced MRI for automatic detection of foci @]@of residual or recurrent disease after prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Parra, N.A.; Orman, Amber; Abramowitz, Matthew; Pollack, Alan; Stoyanova, Radka [University of Miami Miller School of Medicine, Department of Radiation Oncology, Miami, FL (United States); Padgett, Kyle [University of Miami Miller School of Medicine, Department of Radiation Oncology, Miami, FL (United States); University of Miami Miller School of Medicine, Department of Radiology, Miami, FL (United States); Casillas, Victor [University of Miami Miller School of Medicine, Department of Radiology, Miami, FL (United States); Punnen, Sanoj [University of Miami Miller School of Medicine, Department of Urology, Miami, FL (United States)

    2017-01-15

    This study aimed to develop an automated procedure for identifying suspicious foci of residual/recurrent disease in the prostate bed using dynamic contrast-enhanced-MRI (DCE-MRI) in prostate cancer patients after prostatectomy. Data of 22 patients presenting for salvage radiotherapy (RT) with an identified gross tumor volume (GTV) in the prostate bed were analyzed retrospectively. An unsupervised pattern recognition method was used to analyze DCE-MRI curves from the prostate bed. Data were represented as a product of a number of signal-vs.-time patterns and their weights. The temporal pattern, characterized by fast wash-in and gradual wash-out, was considered the ''tumor'' pattern. The corresponding weights were thresholded based on the number (1, 1.5, 2, 2.5) of standard deviations away from the mean, denoted as DCE1.0,.., DCE2.5, and displayed on the T2-weighted MRI. The resultant four volumes were compared with the GTV and maximum pre-RT prostate-specific antigen (PSA) level. Pharmacokinetic modeling was also carried out. Principal component analysis determined 2-4 significant patterns in patients' DCE-MRI. Analysis and display of the identified suspicious foci was performed in commercial software (MIM Corporation, Cleveland, OH, USA). In general, DCE1.0/DCE1.5 highlighted larger areas than GTV. DCE2.0 and GTV were significantly correlated (r = 0.60, p < 0.05). DCE2.0/DCA2.5 were also significantly correlated with PSA (r = 0.52, 0.67, p < 0.05). K{sup trans} for DCE2.5 was statistically higher than the GTV's K{sup trans} (p < 0.05), indicating that the automatic volume better captures areas of malignancy. A software tool was developed for identification and visualization of the suspicious foci in DCE-MRI from post-prostatectomy patients and was integrated into the treatment planning system. (orig.) [German] Entwicklung eines automatischen Analyseverfahrens, um nach Prostatektomie mittels dynamischer kontrastmittelverstaerkter

  15. Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.

    Directory of Open Access Journals (Sweden)

    Yasuhisa Ano

    Full Text Available Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer's disease and to identify the responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD, intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ and hippocampal inflammation (TNF-α and MIP-1α production, and enhancing hippocampal neurotrophic factors (BDNF and GDNF. A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer's disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia.

  16. Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.

    Science.gov (United States)

    Ano, Yasuhisa; Ozawa, Makiko; Kutsukake, Toshiko; Sugiyama, Shinya; Uchida, Kazuyuki; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer's disease and to identify the responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer's disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia.

  17. Preventive Effects of a Fermented Dairy Product against Alzheimer’s Disease and Identification of a Novel Oleamide with Enhanced Microglial Phagocytosis and Anti-Inflammatory Activity

    Science.gov (United States)

    Ano, Yasuhisa; Ozawa, Makiko; Kutsukake, Toshiko; Sugiyama, Shinya; Uchida, Kazuyuki; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer’s disease and to identify the responsible component. Here, in a mouse model of Alzheimer’s disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer’s disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia. PMID:25760987

  18. Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus.

    Directory of Open Access Journals (Sweden)

    Clint L Miller

    Full Text Available Coronary heart disease (CHD is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin is a member of the basic-helix-loop-helix (bHLH transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1 element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β and Wilms tumor 1 (WT1 pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.

  19. Oral administration of Eclipta alba leaf aqueous extract enhances the non-specific immune responses and disease resistance of Oreochromis mossambicus.

    Science.gov (United States)

    Christybapita, D; Divyagnaneswari, M; Michael, R Dinakaran

    2007-10-01

    Immunostimulatory effects of the oral administration of the medicinal plant, Eclipta alba leaf extracts was studied in tilapia, Oreochromis mossambicus. For this purpose, fish were fed for 1, 2 or 3 weeks with diets containing E. alba leaf aqueous extract at 0, 0.01, 0.1 or 1% levels. After each week, non-specific humoral (lysozyme, antiprotease and complement) and cellular (myeloperoxidase content, production of reactive oxygen and nitrogen species) responses and disease resistance against Aeromonas hydrophila were determined. The results indicated that E. alba aqueous extract administered as feed supplement significantly enhanced most of the non-specific immune parameters tested. Among the humoral responses, lysozyme activity significantly increased after feeding with aqueous extract for 1, 2 or 3 weeks. No significant modulation was noticed in all the cellular responses tested after 3 weeks of feeding, while reactive oxygen species production and myeloperoxidase content showed significant enhancement after 1 week of feeding with aqueous extract. When challenged with A. hydrophila after 1, 2 or 3 weeks of feeding, the percentage mortality was significantly reduced in the treated fish. The highest dose of 1% gave better protection than the other doses with the relative percentage survival (RPS) values of 64, 75 and 32 after feeding for 1, 2 and 3 weeks respectively. The results indicate that dietary intake of E. alba aqueous leaf extract enhances the non-specific immune responses and disease resistance of O. mossambicus against A. hydrophila.

  20. Synergistic effects of plant defense elicitors and Trichoderma harzianum on enhanced induction of antioxidant defense system in tomato against Fusarium wilt disease.

    Science.gov (United States)

    Zehra, Andleeb; Meena, Mukesh; Dubey, Manish Kumar; Aamir, Mohd; Upadhyay, R S

    2017-11-02

    Plant defense against their pathogens can be induced by a complex network of different inducers. The present study investigates the synergistic effect of Trichoderma harzianum, exogenous salicylic acid (SA) and methyl jasmonate (MeJA) over the response and regulation of the antioxidant defense mechanisms and lipid peroxidation in tomato plants against Fusarium wilt disease. In the present work, tomato plants were infected by Fusarium oxysporum f. sp. lycopersici 3 days after inoculated with T. harzianum and/or sprayed daily for 3 days with chemical inducers (SA and MeJA). Plants were analysed at 0, 24, 48, 72 and 96 h after inoculation with Fusarium oxysporum f. sp. lycopersici. Infection of tomato plants by pathogen led to strong reduction in the dry weight of roots and shoots with the enhanced concentration of H 2 O 2 and varying degree of lipid peroxidation. Concurrently, exogenous SA, when applied with pathogen greatly enhanced H 2 O 2 content as well as activities of antioxidant enzymes except catalase (CAT) and ascorbate peroxidase (APx). The pathogen challenged plants pretreated with T. harzianum and MeJA together exhibited less lipid peroxidation and as well as the elevated level of ascorbic acid and enhanced activities of antioxidant enzymes. All applied treatments protected tomato seedlings against Fusarium wilt disease but the percentage of protection was found higher in plants pretreated with the combination of T. harzianum and chemical inducers.

  1. Can health systems be enhanced for optimal health services through disease-specific programs? Results of field studies in Viet Nam and Cambodia.

    Science.gov (United States)

    Egami, Y; Fujita, N; Akashi, H; Matsumoto, Y; Ohara, H; Takeuchi, M

    2012-02-01

    Developing better health systems is the key to delivering optimal health services, although more evidence of effective strategies to do so is needed. Field surveys were conducted in Viet Nam and Cambodia to identify best practices in addressing health system bottlenecks to scale up disease control programs. The two countries were compared over time using a framework for analysis developed by the authors. In Viet Nam, a health system was in place for decades at the central to municipal levels, although it was fragile until the 1990s, when the government started taking measures. In Cambodia, the previous health system had been destroyed during previous internal conflict. In the post-conflict period, the health system was rebuilt with support for programs followed by centralization of health services. In different settings, different measures were taken to deal with similar bottlenecks. In Cambodia, vertical programs were dominant, so the government sought to centralize drug management to deal with shortages of essential drugs, while Viet Nam sought to mobilize resources to ensure drug distribution at all levels. This study shows there is no single successful approach to health systems, and a systemic approach needs to be taken because elimination of one bottleneck may reveal another. Efforts to enhance disease-specific programs may not always contribute to overall enhancement of the health system, and the best possible approach may not be the same in different countries. Further study is needed to explore common issues and principles for effective strategies to enhance health systems in different contexts.

  2. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  3. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    International Nuclear Information System (INIS)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-01-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  4. Neovascularization in Vertebral Artery Atheroma-A Dynamic Contrast-Enhanced Magnetic Resonance Imaging-Based Comparative Study in Patients with Symptomatic and Asymptomatic Carotid Artery Disease.

    Science.gov (United States)

    Usman, Ammara; Yuan, Jianmin; Patterson, Andrew J; Graves, Martin J; Varty, Kevin; Sadat, Umar; Gillard, Jonathan H

    2018-05-24

    Atherosclerosis is a systemic inflammatory disease intertwined with neovascularization. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables the assessment of plaque neovascularization. This study aimed to explore the systemic nature of atherosclerosis by assessing difference in severity of neovascularization as quantified by DCE-MRI of vertebral arteries (VAs) between patients with symptomatic and asymptomatic carotid artery disease. Ten consecutive patients with asymptomatic VA stenosis and concomitant symptomatic carotid artery disease (group 1) and 10 consecutive patients with asymptomatic VA stenosis and concomitant asymptomatic carotid artery disease (group 2) underwent 3-dimensional DCE-MRI of their cervical segment of VAs. A previously validated pharmacokinetic modeling approach was used for DCE-MRI analysis. K trans was calculated in the adventitia and plaque as a measure of neovessel permeability. Both patient groups were comparable for demographics and comorbidities. Mean luminal stenosis was comparable for both groups (54.4% versus 52.27%, P = .32). Group 1 had higher adventitial K trans and plaque K trans (.08 ± .01 min -1 , .07 ± .01 min -1 ) compared with Group 2 (.06 ± .01 min -1 , .06 ± .01 min -1 ) (P = .004 and .03, respectively). Good correlation was present among the two image analysts (intraclass correlation coefficient = .78). Vertebral Artery atheroma of patients with symptomatic carotid artery disease had increased neovessel permeability compared with the patients with asymptomatic carotid artery disease. These findings are consistent with the hypothesis that atherosclerosis is a systemic inflammatory disease. The VA atherosclerosis is likely to have increased severity of neovascularization if another arterial territory is symptomatic in the same patient cohort. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Strategies to enhance rational use of antibiotics in hospital : a guideline by the German Society for Infectious Diseases

    NARCIS (Netherlands)

    de With, K.; Allerberger, F.; Amann, S.; Apfalter, P.; Brodt, H. -R.; Eckmanns, T.; Fellhauer, M.; Geiss, H. K.; Janata, O.; Krause, R.; Lemmen, S.; Meyer, E.; Mittermayer, H.; Porsche, U.; Presterl, E.; Reuter, S.; Sinha, B.; Strauss, R.; Wechsler-Foerdoes, A.; Wenisch, C.; Kern, W. V.

    In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was

  6. Differentiation of hypertensive heart disease with hypertrophy and hepertrophic cardiomyopathy using consecutive time-course images of Gd-DTPA enhanced MRI

    International Nuclear Information System (INIS)

    Ochiai, Kouichi; Isibashi, Yutaka; Shimada, Toshio; Tsukihashi, Hironori; Sato, Hidetoshi; Kitamura, Jun; Morioka, Shigefumi; Kawamitsu, Hideaki; Sugimura, Kazuro

    1996-01-01

    We used consecutive time-course Gd-DTPA contrast magnetic resonance images to differentiate hypertrophic cardiomyopathy (HCM) from hypertensive heart disease with hypertrophy (HHD). Seventeen patients with HCM, 6 patients with HHD and 5 normal subjects (control) were studied. ECG-gated MRI with 1.5T system was performed before and after intravenous injection of Gd-DTPA (0.1mmol/Kg) using spin echo sequence. Gd-DTPA enhanced MRI was repeated every 10 to 55 minutes. We measured signal intensity (SI) of midleft ventricular myocardium and skeletal muscle, and then calculated the ratio between myocardial SI and skeletal muscle SI. Myocardium was enhanced by Gd-DTPA in all patients. However, there was difference in the decay of enhancement effect by Gd-DTPA between HCM and HHD. The decay in HCM was more slowly than in both HHD and control. There was no difference in the decay between HHD and control. The difference in the decay between HCM and HHD became significant 25 minutes after Gd-DTPA injection and lasted until 55 minutes. We conclude that the time-course of the decay of enhancement effect by Gd-DTPA is helpful to differentiate HCM from HHD and the difference of the decay might reflect structural changes of myocardium. (author)

  7. Influence of local habitat features on disease avoidance by Caribbean spiny lobsters in a casita-enhanced bay.

    Science.gov (United States)

    Briones-Fourzán, Patricia; Candia-Zulbarán, Rebeca I; Negrete-Soto, Fernando; Barradas-Ortiz, Cecilia; Huchin-Mian, Juan P; Lozano-Álvarez, Enrique

    2012-08-27

    In Bahía de la Ascensión, Mexico, 'casitas' (large artificial shelters) are extensively used to harvest Caribbean spiny lobsters Panulirus argus. After the discovery of a pathogenic virus, Panulirus argus virus 1 (PaV1), in these lobsters, laboratory experiments revealed that PaV1 could be transmitted by contact and through water, and that lobsters avoided shelters harboring diseased conspecifics. To examine these issues in the context of casitas, which typically harbor multiple lobsters of all sizes, we examined the distribution and aggregation patterns of lobsters in the absence/presence of diseased conspecifics (i.e. visibly infected with PaV1) in 531 casitas distributed over 3 bay zones, 1 poorly vegetated ('Vigía Chico', average depth: 1.5 m) and 2 more extensively vegetated ('Punta Allen': 2.5 m; 'Los Cayos': 2.4 m). All zones had relatively high indices of predation risk. Using several statistical approaches, we found that distribution parameters of lobsters were generally not affected by the presence of diseased conspecifics in casitas. Interestingly, however, in the shallower and less vegetated zone (Vigía Chico), individual casitas harbored more lobsters and lobsters were actually more crowded in casitas containing diseased conspecifics, yet disease prevalence was the lowest in lobsters of all sizes. These results suggest that (1) investment in disease avoidance by lobsters is partially modulated by local habitat features, (2) contact transmission rates of PaV1 may be lower in nature than in the laboratory, and (3) water-borne transmission rates may be lower in shallow, poorly vegetated habitats more exposed to solar ultraviolet radiation, which can damage viral particles.

  8. From habits of attrition to modes of inclusion: enhancing the role of private practitioners in routine disease surveillance.

    Science.gov (United States)

    Phalkey, Revati K; Butsch, Carsten; Belesova, Kristine; Kroll, Marieke; Kraas, Frauke

    2017-08-25

    Private practitioners are the preferred first point of care in a majority of low and middle-income countries and in this position, best placed for the surveillance of diseases. However their contribution to routine surveillance data is marginal. This systematic review aims to explore evidence with regards to the role, contribution, and involvement of private practitioners in routine disease data notification. We examined the factors that determine the inclusion of, and the participation thereof of private practitioners in disease surveillance activities. Literature search was conducted using the PubMed, Web of Knowledge, WHOLIS, and WHO-IRIS databases to identify peer-reviewed and gray full-text documents in English with no limits for year of publication or study design. Forty manuscripts were reviewed. The current participation of private practitioners in disease surveillance efforts is appalling. The main barriers to their participation are inadequate knowledge leading to unsatisfactory attitudes and misperceptions that influence their practices. Complicated reporting mechanisms with unclear guidelines, along with unsatisfactory attitudes on behalf of the government and surveillance program managers also contribute to the underreporting of cases. Infrastructural barriers especially the availability of computers and skilled human resources are critical to improving private sector participation in routine disease surveillance. The issues identified are similar to those for underreporting within the Integrated infectious Disease Surveillance and Response systems (IDSR) which collects data mainly from public healthcare facilities. We recommend that surveillance program officers should provide periodic training, supportive supervision and offer regular feedback to the practitioners from both public as well as private sectors in order to improve case notification. Governments need to take leadership and foster collaborative partnerships between the public and private

  9. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schafer, C.; Schwarz, E.

    2008-01-01

    Aim: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development...... of ALD in animal experiments, the hypothesis of the present retrospective cross-sectional study was that gender-dependent (micro-) nutrient intake in patients with ALD may cause the higher susceptibility of women to this disease. Methods: In 210 patients (male: 158, female: 52) with different stages...

  10. Diagnosis of occlusive arterial disease and assessment of IVR with fat-suppressed gadolinium-enhanced three-dimensional MR angiography

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Gemma, Kazuhito; Kawamata, Hiroshi; Okajima, Yuhji; Watari, Jun; Kumazaki, Tatsuo [Nippon Medical School, Tokyo (Japan); Maki, Toshio; Tsuchihashi, Toshio

    1996-10-01

    Fat-suppressed gadolinium-enhanced three-dimensional MR angiography (FS-CE-3D-MRA) was performed to make a diagnosis of occlusive arterial disease and evaluate the effectiveness of IVR treatment for it. FS-CE-3D-MRA delineated stenosis of common iliac arteries, which was confirmed by X-ray angiography. FS-CE-3D-MRA also detected ulcerated plaque and arterial wall irregularity. The effectiveness of IVR as atherectomy and stent placement was accurately assessed with FS-CE-3D-MRA. FS-CE-3D-MRA was useful in evaluating occlusive arterial disease with short examination times and high spatial resolution, although iliac circumflexial arteries were not detected by this technique. (author)

  11. Application of Cavity Enhanced Absorption Spectroscopy to the Detection of Nitric Oxide, Carbonyl Sulphide, and Ethane—Breath Biomarkers of Serious Diseases

    Science.gov (United States)

    Wojtas, Jacek

    2015-01-01

    The paper presents one of the laser absorption spectroscopy techniques as an effective tool for sensitive analysis of trace gas species in human breath. Characterization of nitric oxide, carbonyl sulphide and ethane, and the selection of their absorption lines are described. Experiments with some biomarkers showed that detection of pathogenic changes at the molecular level is possible using this technique. Thanks to cavity enhanced spectroscopy application, detection limits at the ppb-level and short measurements time (ethane, respectively. The conducted experiments show that this type of diagnosis would significantly increase chances for effective therapy of some diseases. Additionally, it offers non-invasive and real time measurements, high sensitivity and selectivity as well as minimizing discomfort for patients. For that reason, such sensors can be used in screening for early detection of serious diseases. PMID:26091398

  12. Anti-IL-2 treatment impairs the expansion of T(reg cell population during acute malaria and enhances the Th1 cell response at the chronic disease.

    Directory of Open Access Journals (Sweden)

    Cláudia A Zago

    Full Text Available Plasmodium chabaudi infection induces a rapid and intense splenic CD4(+ T cell response that contributes to both disease pathogenesis and the control of acute parasitemia. The subsequent development of clinical immunity to disease occurs concomitantly with the persistence of low levels of chronic parasitemia. The suppressive activity of regulatory T (T(reg cells has been implicated in both development of clinical immunity and parasite persistence. To evaluate whether IL-2 is required to induce and to sustain the suppressive activity of T(reg cells in malaria, we examined in detail the effects of anti-IL-2 treatment with JES6-1 monoclonal antibody (mAb on the splenic CD4(+ T cell response during acute and chronic P. chabaudi AS infection in C57BL/6 mice. JES6-1 treatment on days 0, 2 and 4 of infection partially inhibits the expansion of the CD4(+CD25(+Foxp3(+ cell population during acute malaria. Despite the concomitant secretion of IL-2 and expression of high affinity IL-2 receptor by large CD4(+ T cells, JES6-1 treatment does not impair effector CD4(+ T cell activation and IFN-γ production. However, at the chronic phase of the disease, an enhancement of cellular and humoral responses occurs in JES6-1-treated mice, with increased production of TNF-α and parasite-specific IgG2a antibodies. Furthermore, JES6-1 mAb completely blocked the in vitro proliferation of CD4(+ T cells from non-treated chronic mice, while it further increased the response of CD4(+ T cells from JES6-1-treated chronic mice. We conclude that JES6-1 treatment impairs the expansion of T(reg cell population during early P. chabaudi malaria and enhances the Th1 cell response in the late phase of the disease.

  13. Frontal and temporal lobe contributions to emotional enhancement of memory in behavioral-variant frontotemporal dementia and Alzheimer's disease

    OpenAIRE

    Kumfor, Fiona; Irish, Muireann; Hodges, John R.; Piguet, Olivier

    2014-01-01

    Emotional events gain special priority in how they are remembered, with emotionally arousing events typically recalled more vividly and with greater confidence than non-emotional events. In dementia, memory and emotion processing are affected to varying degrees, however, whether emotional enhancement of memory for complex ecologically-valid events is differentially affected across dementia syndromes remains unclear, with previous studies examining effects of emotion on simple visual recogniti...

  14. Enhanced levels of mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 in patients with Azheimer disease and multiple sclerosis

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Bocková, Markéta; Hegnerová, Kateřina; Bartoš, A.; Klaschka, J.; Říčný, J.; Řípová, D.; Homola, Jiří

    2009-01-01

    Roč. 10, č. 5 (2009), s. 1174-1179 ISSN 1742-206X R&D Projects: GA MZd NR9322 Institutional research plan: CEZ:AV0Z20670512 Keywords : 17beta-HSD 10 * Alzheimer disease * SPR sensor Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 4.015, year: 2009

  15. Enhanced sensitivity in detection of antiviral antibody responses using biotinylation of foot-and-mouth disease virus (FMDV) capsids

    Science.gov (United States)

    Analysis of the immune response to infection of livestock by foot-and-mouth disease virus (FMDV) is most often reported as the serum antibody response to the virus. While measurement of neutralizing antibody has been sensitive and specific, measurements of the quality of the antibody response are le...

  16. Seed treatments enhance photosynthesis in maize seedlings by reducing infection with Fusarium spp. and consequent disease development in maize

    Science.gov (United States)

    The effects of a seed treatment on early season growth, seedling disease development, incidence Fusarium spp. infection, and photosynthetic performance of maize were evaluated at two locations in Iowa in 2007. Maize seed was either treated with Cruiser 2Extreme 250 ® (fludioxonil + azoxystrobin + me...

  17. Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Shen, Jianlin; Rasmussen, Marianne; Dong, Qi-Rong

    2017-01-01

    increase in NQO1 gene expression in CKD 1-5 (n = 29; 3.5 for NQO1/ribosomal protein L41; p disease prevalence was higher in CKD 1-5 patients with higher compared to those with lower NQO1 gene expression (p = 0...

  18. Booster Sessions Enhance the Long-Term Effectiveness of Spaced Retrieval in Older Adults with Probable Alzheimer's Disease

    Science.gov (United States)

    Cherry, Katie E.; Hawley, Karri S.; Jackson, Erin M.; Boudreaux, Emily O.

    2009-01-01

    Six older adults with probable Alzheimer's disease (AD) were trained to recall a name-face association using the spaced retrieval technique. In this study, we retested these persons in a 6-month follow-up program. For half of the participants, three booster sessions were administered at 6, 12, and 18 weeks after original training to promote…

  19. Spaced Retrieval Enhances Memory for a Name-Face-Occupation Association in Older Adults with Probable Alzheimer's Disease

    Science.gov (United States)

    Cherry, Katie E.; Walvoord, Ashley A. G.; Hawley, Karri S.

    2010-01-01

    The authors trained 4 older adults with probable Alzheimer's disease to recall a name-face-occupation association using the spaced retrieval technique. Six training sessions were administered over a 2-week period. On each trial, participants selected a target photograph and stated the target name and occupation at increasingly longer retention…

  20. Prediction of presence of kidney disease in a general patient population undergoing intravenous iodinated contrast enhanced computed tomography.

    Science.gov (United States)

    Moos, Shira I; Stoker, Jaap; Nagan, Gajenthiran; de Weijert, Roderick S; van Vemde, David N H; Bipat, Shandra

    2014-06-01

    To assess which risk factors can be used to reduce superfluous estimated glomerular filtration rate (eGFR) measurements before intravenous contrast medium administration. In consecutive patients, all decreased eGFR risk factors were assessed: diabetes mellitus (DM), history of urologic/nephrologic disease (HUND), nephrotoxic medication, cardiovascular disease, hypertension, age > 60 years, anaemia, malignancy and multiple myeloma/M. Waldenström. We studied four models: (1) all risk factors, (2) DM, HUND, hypertension, age > 60 years; (3) DM, HUND, cardiovascular disease, hypertension; (4) DM, HUND, age > 75 years and congestive heart failure. For each model, association with eGFR < 60 ml/min/1.73 m(2) or eGFR < 45 ml/min/1.73 m(2) was studied. A total of 998 patients, mean age 59.94 years were included; 112 with eGFR < 60 ml/min/1.73 m(2) and 30 with eGFR < 45 ml/min/1.73 m(2). Model 1 detected 816 patients: 108 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 2 detected 745 patients: 108 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 3 detected 622 patients: 100 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 4 detected 440 patients: 86 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Associations were significant (p < 0.001). Model 4 is most effective, resulting in the lowest proportion of superfluous eGFR measurements while detecting all patients with eGFR < 45 ml/min/1.73 m(2) and most with eGFR < 60 ml/min/1.73 m(2). A major risk factor for contrast-induced nephropathy (CIN) is kidney disease. Risk factors are used to identify patients with pre-existent kidney disease. Evidence for risk factors to identify patients with kidney disease is limited. The number of eGFR measurements to detect kidney disease can be reduced.

  1. Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases? [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Daniel Ortuno

    2016-02-01

    Full Text Available A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation of protein aggregates such as α-synuclein in Parkinson’s disease, TDP-43 in ALS, and tau in Alzheimer’s disease. Enhancing intracellular clearance of aggregation-prone proteins is a plausible strategy for slowing progression of neurodegenerative diseases and there is great interest in identifying molecular targets that control protein turnover. One of the main routes for protein degradation is through the proteasome, a multisubunit protease that degrades proteins that have been tagged with a polyubiquitin chain by ubiquitin activating and conjugating enzymes. Published data from cellular models indicate that Ubiquitin-specific protease 14 (USP14, a deubiquitinating enzyme (DUB, slows the degradation of tau and TDP-43 by the proteasome and that an inhibitor of USP14 increases the degradation of these substrates. We conducted similar experiments designed to evaluate tau, TDP-43, or α-synuclein levels in cells after overexpressing USP14 or knocking down endogenous expression by siRNA.

  2. Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases? [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Daniel Ortuno

    2016-04-01

    Full Text Available A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation of protein aggregates such as α-synuclein in Parkinson’s disease, TDP-43 in ALS, and tau in Alzheimer’s disease. Enhancing intracellular clearance of aggregation-prone proteins is a plausible strategy for slowing progression of neurodegenerative diseases and there is great interest in identifying molecular targets that control protein turnover. One of the main routes for protein degradation is through the proteasome, a multisubunit protease that degrades proteins that have been tagged with a polyubiquitin chain by ubiquitin activating and conjugating enzymes. Published data from cellular models indicate that Ubiquitin-specific protease 14 (USP14, a deubiquitinating enzyme (DUB, slows the degradation of tau and TDP-43 by the proteasome and that an inhibitor of USP14 increases the degradation of these substrates. We conducted similar experiments designed to evaluate tau, TDP-43, or α-synuclein levels in cells after overexpressing USP14 or knocking down endogenous expression by siRNA.

  3. The treatable intellectual disability APP www.treatable-id.org: A digital tool to enhance diagnosis & care for rare diseases

    Science.gov (United States)

    2012-01-01

    Background Intellectual disability (ID) is a devastating and frequent condition, affecting 2-3% of the population worldwide. Early recognition of treatable underlying conditions drastically improves health outcomes and decreases burdens to patients, families and society. Our systematic literature review identified 81 such inborn errors of metabolism, which present with ID as a prominent feature and are amenable to causal therapy. The WebAPP translates this knowledge of rare diseases into a diagnostic tool and information portal. Methods & results Freely available as a WebAPP via http://www.treatable-id.org and end 2012 via the APP store, this diagnostic tool is designed for all specialists evaluating children with global delay / ID and laboratory scientists. Information on the 81 diseases is presented in different ways with search functions: 15 biochemical categories, neurologic and non-neurologic signs & symptoms, diagnostic investigations (metabolic screening tests in blood and urine identify 65% of all IEM), therapies & effects on primary (IQ/developmental quotient) and secondary outcomes, and available evidence For each rare condition a ‘disease page’ serves as an information portal with online access to specific genetics, biochemistry, phenotype, diagnostic tests and therapeutic options. As new knowledge and evidence is gained from expert input and PubMed searches this tool will be continually updated. The WebAPP is an integral part of a protocol prioritizing treatability in the work-up of every child with global delay / ID. A 3-year funded study will enable an evaluation of its effectiveness. Conclusions For rare diseases, a field for which financial and scientific resources are particularly scarce, knowledge translation challenges are abundant. With this WebAPP technology is capitalized to raise awareness for rare treatable diseases and their common presenting clinical feature of ID, with the potential to improve health outcomes. This innovative digital

  4. The treatable intellectual disability APP www.treatable-id.org: A digital tool to enhance diagnosis & care for rare diseases

    Directory of Open Access Journals (Sweden)

    van Karnebeek Clara D M

    2012-07-01

    Full Text Available Abstract Background Intellectual disability (ID is a devastating and frequent condition, affecting 2-3% of the population worldwide. Early recognition of treatable underlying conditions drastically improves health outcomes and decreases burdens to patients, families and society. Our systematic literature review identified 81 such inborn errors of metabolism, which present with ID as a prominent feature and are amenable to causal therapy. The WebAPP translates this knowledge of rare diseases into a diagnostic tool and information portal. Methods & results Freely available as a WebAPP via http://www.treatable-id.org and end 2012 via the APP store, this diagnostic tool is designed for all specialists evaluating children with global delay / ID and laboratory scientists. Information on the 81 diseases is presented in different ways with search functions: 15 biochemical categories, neurologic and non-neurologic signs & symptoms, diagnostic investigations (metabolic screening tests in blood and urine identify 65% of all IEM, therapies & effects on primary (IQ/developmental quotient and secondary outcomes, and available evidence For each rare condition a ‘disease page’ serves as an information portal with online access to specific genetics, biochemistry, phenotype, diagnostic tests and therapeutic options. As new knowledge and evidence is gained from expert input and PubMed searches this tool will be continually updated. The WebAPP is an integral part of a protocol prioritizing treatability in the work-up of every child with global delay / ID. A 3-year funded study will enable an evaluation of its effectiveness. Conclusions For rare diseases, a field for which financial and scientific resources are particularly scarce, knowledge translation challenges are abundant. With this WebAPP technology is capitalized to raise awareness for rare treatable diseases and their common presenting clinical feature of ID, with the potential to improve health outcomes

  5. A comparison of non-contrast and contrast-enhanced MRI in the initial stage of Legg-Calve-Perthes disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Harry K.W. [Texas Scottish Rite Hospital for Children, Center of Excellence in Hip Disorders, Dallas, TX (United States); University of Texas Southwestern, Department of Orthopedic Surgery, Dallas, TX (United States); Kaste, Sue [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee School of Health Sciences, Department of Radiology, Memphis, TN (United States); Dempsey, Molly; Wilkes, David [Texas Scottish Rite Hospital for Children, Department of Radiology, Dallas, TX (United States)

    2013-09-15

    A prognostic indicator of outcome for Legg-Calve-Perthes disease (LCP) is needed to guide treatment decisions during the initial stage of the disease (stage 1), before deformity occurs. Radiographic prognosticators are applicable only after fragmentation (stage II). We investigated pre- and postcontrast MRI in depicting stage I femoral head involvement. Thirty children with stage I LCP underwent non-contrast coronal T1 fast spin-echo (FSE) and corresponding postcontrast fat-suppressed T1-weighted fast spin-echo (FSE) sequences to quantify the extent of femoral head involvement. Three pediatric radiologists and one pediatric orthopedic surgeon independently measured central head involvement. Interobserver reliability of percent head involvement using non-contrasted MR images had intraclass correlation coefficient (ICC) of 0.72. Postcontrast MRI improved interobserver reliability (ICC 0.82). Qualitatively, the area of involvement was more clearly visible on contrast-enhanced MRI. A comparison of results obtained by each observer using the two MRI techniques showed no correlation. ICC ranged from -0.08 to 0.03 for each observer. Generally, greater head involvement was depicted by contrast compared with non-contrast MRI (Pearson r = -0.37, P = 0.04). Pre- and postcontrast MRI assess two different components of stage I LCP. However, contrast-enhanced MRI more clearly depicts the area of involvement. (orig.)

  6. Dynamic Gd-DTPA enhanced breath-hold 1.5 t MRI of normal lungs and patients with interstitial lung disease and pulmonary nodules: preliminary results

    International Nuclear Information System (INIS)

    Semelka, R.C.; Maycher, B.; Shoenut, J.P.; Kroeker, R.; Griffin, P.; Lertzman, M.

    1992-01-01

    A FLASH technique was used, which encompassed the entire thorax in the transverse plane, before and after dynamic intravenous injection of godalinium DTPA (Gd-DTPA) to study 7 patients with normal lungs, 12 patients with interstitial lung disease (ILD), and 11 patients with pulmonary nodules. Comparative CT studies were obtained within 2 weeks of the MRI study in the patients with lung disease. Quantitative signal intensity (SI) measurements were performed. Qualitative evaluation of lung parenchyma was determined in a prospective blinded fashion, and in the normal group comparison was made with the CT images. In normal patients, SI of lung parenchyma increased by 7.7±1.3%. On precontrast images, second-order pulmonary branchings were visible while post-contrast, fifth- to sixth-order branches were apparent. In patients with ILD, interstitial changes enhanced to a variable extent, increases in SI ranging from minimal (49.9%) to substantial (308.4%). Detection of pulmonary nodules improved following contrast injection. The minimum lesion size detectable decreased from 8 mm precontrast to 5 mm post-contrast. Percentage contrast enhancement was greater for malignant nodules (124.2±79.7%) than benign nodules (5.8±4.7%) (p<0.01). (orig.)

  7. Pest and disease resistance enhanced by heterologous suppression of a Nicotiana plumbaginifolia cytochrome P450 gene CYP72A2.

    Science.gov (United States)

    Smigocki, Ann C; Wilson, Dennis

    2004-12-01

    The functional role of the Nicotiana plumbaginifolia cytochrome P450 gene CYP72A2 was investigated in transgenic plants. N. tabacum plants transformed with a sense or antisense CYP72A2 construct exhibited diminished heights, branched stems, smaller leaves and deformed flowers. Western blot analysis revealed reduced levels of a 58 kDa protein corresponding to CYP72A2, suggesting that the CYP72A2 homolog was suppressed in the sense and antisense plants. Transgenic plants had increased resistance to Manduca sexta larvae that consumed about 35 to 90 less of transgenic versus control leaves. A virulent strain of Pseudomonas syringae pv. tabaci induced a disease-limiting response followed by a delayed and decreased development of disease symptoms in the transgenics. CYP72A2 gene mediated resistance suggests that the plant-pest or -pathogen interactions may have been modified by changes in bioactive metabolite pools.

  8. A tick mannose-binding lectin inhibits the vertebrate complement cascade to enhance transmission of the Lyme disease agent

    OpenAIRE

    Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; DePonte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J.T.H.; van Dam, Alje P.; van der Poll, Tom; van ’t Veer, Cornelis; Hovius, Joppe W.; Fikrig, Erol

    2011-01-01

    The Lyme disease agent, Borrelia burgdorferi, is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8 that reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade resulting in impaired neutrophil phagocytosis and chemotaxis, and diminished Borrelia lysi...

  9. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schäfer, C.; Schwarz, E.

    2008-01-01

    AIM: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development......, the data of calculated daily macro- and micronutrient intake do not suggest any explicit influence of gender-specific nutrition in the development of ALD....

  10. Contrast-enhanced MRI compared with the physical examination in the evaluation of disease activity in juvenile idiopathic arthritis

    International Nuclear Information System (INIS)

    Hemke, Robert; Maas, Mario; Veenendaal, Mira van; Kuijpers, Taco W.; Dolman, Koert M.; Rossum, Marion A.J. van; Berg, J.M. van den

    2014-01-01

    To assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients. Consecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6 % female; mean age, 12.9 years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions. Inter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC] = 0.87-0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (P = 0.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9 %) with clinically inactive disease. Of JIA patients considered clinically active, 48.6 % showed no signs of MRI-based synovitis. MRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35 % of presumed clinically inactive patients. (orig.)

  11. Identification of imaging predictors discriminating different primary liver tumours in patients with chronic liver disease on gadoxetic acid-enhanced MRI: a classification tree analysis

    International Nuclear Information System (INIS)

    Park, Hyun Jeong; Jang, Kyung Mi; Kang, Tae Wook; Song, Kyoung Doo; Kim, Seong Hyun; Kim, Young Kon; Cha, Dong Ik; Kim, Joungyoun; Goo, Juna

    2016-01-01

    To identify predictors for the discrimination of intrahepatic cholangiocarcinoma (IMCC) and combined hepatocellular-cholangiocarcinoma (CHC) from hepatocellular carcinoma (HCC) for primary liver cancers on gadoxetic acid-enhanced MRI among high-risk chronic liver disease (CLD) patients using classification tree analysis (CTA). A total of 152 patients with histopathologically proven IMCC (n = 40), CHC (n = 24) and HCC (n = 91) were enrolled. Tumour marker and MRI variables including morphologic features, signal intensity, and enhancement pattern were used to identify tumours suspicious for IMCC and CHC using CTA. On CTA, arterial rim enhancement (ARE) was the initial splitting predictor for assessing the probability of tumours being IMCC or CHC. Of 43 tumours that were classified in a subgroup on CTA based on the presence of ARE, non-intralesional fat, and non-globular shape, 41 (95.3 %) were IMCCs (n = 29) or CHCs (n = 12). All 24 tumours showing fat on MRI were HCCs. The CTA model demonstrated sensitivity of 84.4 %, specificity of 97.8 %, and accuracy of 92.3 % for discriminating IMCCs and CHCs from HCCs. We established a simple CTA model for classifying a high-risk group of CLD patients with IMCC and CHC. This model may be useful for guiding diagnosis for primary liver cancers in patients with CLD. (orig.)

  12. Garlic-Derived S-Allylmercaptocysteine Ameliorates Nonalcoholic Fatty Liver Disease in a Rat Model through Inhibition of Apoptosis and Enhancing Autophagy

    Science.gov (United States)

    Fung, Man-Lung; Liong, Emily C.; Chang, Raymond Chuen Chung; Ching, Yick-Pang; Tipoe, George L.

    2013-01-01

    Our previous study demonstrated that administration of garlic-derived antioxidant S-allylmercaptocysteine (SAMC) ameliorated hepatic injury in a nonalcoholic fatty liver disease (NAFLD) rat model. Our present study aimed to investigate the mechanism of SAMC on NAFLD-induced hepatic apoptosis and autophagy. Adult female rats were fed with a high-fat diet for 8 weeks to develop NAFLD with or without intraperitoneal injection of 200 mg/kg SAMC for three times per week. During NAFLD development, increased apoptotic cells and caspase-3 activation were observed in the liver. Increased apoptosis was modulated through both intrinsic and extrinsic apoptotic pathways. NAFLD treatment also enhanced the expression of key autophagic markers in the liver with reduced activity of LKB1/AMPK and PI3K/Akt pathways. Increased expression of proapoptotic regulator p53 and decreased activity of antiautophagic regulator mTOR were also observed. Administration of SAMC reduced the number of apoptotic cells through downregulation of both intrinsic and extrinsic apoptotic mechanisms. SAMC also counteracted the effects of NAFLD on LKB1/AMPK and PI3K/Akt pathways. Treatment with SAMC further enhanced hepatic autophagy by regulating autophagic markers and mTOR activity. In conclusion, administration of SAMC during NAFLD development in rats protects the liver from chronic injury by reducing apoptosis and enhancing autophagy. PMID:23861709

  13. 2D ultrasonography and contrast enhanced ultrasound for the evaluation of cavitating mesenteric lymph node syndrome in a patient with refractory celiac disease and enteropathy T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Pojoga Cristina

    2013-02-01

    Full Text Available Abstract Background The cavitating mesenteric lymph node syndrome (CMLNS is a rare manifestation of celiac disease, with an estimated mortality rate of 50%. Specific infections and malignant lymphoma may complicate its clinical course and contribute to its poor prognosis. Diagnosing the underlying cause of CMLNS can be challenging. This is the first report on contrast enhanced ultrasound (CEUS findings in enteropathy associated T-cell lymphoma (EATL complicating CMLNS in a gluten-free compliant patient with persistent symptoms and poor outcome. Case presentation We present the case of a 51-year old Caucasian male patient, diagnosed with celiac disease and CMLNS. Despite his compliance to the gluten-free diet the symptoms persisted and we eventually considered the possible development of malignancy. No mucosal changes suggestive of lymphoma were identified with capsule endoscopy. Low attenuation mesenteric lymphadenopathy, without enlarged small bowel segments were seen on computed tomography. CEUS revealed arterial rim enhancement around the necrotic mesenteric lymph nodes, without venous wash-out. No malignant cells were identified on laparoscopic mesenteric lymph nodes biopsies. The patient died due to fulminant liver failure 14 months later; the histopathological examination revealed CD3/CD30-positive atypical T-cell lymphocytes in the liver, mesenteric tissue, spleen, gastric wall, kidney, lung and bone marrow samples; no malignant cells were present in the small bowel samples. Conclusions CEUS findings in EATL complicating CMLNS include arterial rim enhancement of the mesenteric tissue around the cavitating lymph nodes, without venous wash-out. This vascular pattern is not suggestive for neoangiogenesis, as arteriovenous shunts from malignant tissues are responsible for rapid venous wash-out of the contrast agent. CEUS failed to provide a diagnosis in this case.

  14. Evaluation of rectus extraocular muscles using dynamic contrast-enhanced MR imaging in patients with Graves' ophthalmopathy for assessment of disease activity

    International Nuclear Information System (INIS)

    Jiang, Hong; Wang, Zhenchang; Xian, Junfang; Li, Jing; Chen, Qinghua; Ai, Likun

    2012-01-01

    Background. It is important to assess the activity of Graves' ophthalmopathy (GO) for planning optimal treatment strategy. Dynamic contrast-enhanced MR imaging (DCE-MRI) is a technique for assessment of microcirculation status. The correlation between disease activity and the microcirculation characteristics of extraocular muscles (EOMs) has been demonstrated in GO. Purpose. To investigate the changes of rectus EOMs in patients with active vs. inactive GO using DCE-MRI, and to evaluate the value of DCE-MRI in assessing the activity of GO. Material and Methods. Rectus EOMs of 20 healthy controls, 18 patients with active GO, and 16 patients with inactive GO were studied. The signal intensity (SI) of rectus EOMs on T 2 W images was evaluated. Regions of interest were placed on each rectus on DCE-MRI images. The DCE-MRI parameters including time to peak enhancement (T peak ), enhancement ratio (ER), and wash-out ratio (WR) were calculated. Results. There were significant differences in SI and T peak , ER and WR values among the three groups (P = 0.000). However, there was no significant difference in SI between the active and inactive groups (P = 0.07). Tpeak values of each rectus were significantly increased in inactive group compared with the active group (P peak ), maximum ER (maxER) and maximum WR (maxWR) (P peak , maxER and maxWR were 156.98s, 1.31 and 13.50% respectively, giving positive predictive values of 68.00%, 88.90%, and 94.44% for the assessment of disease activity. Conclusion. DCE-MRI could demonstrate the micro circulatory changes of rectus EOMs in both active and inactive GO, and this MRI method is a useful tool in differentiating active from inactive GO

  15. Developing community-driven quality improvement initiatives to enhance chronic disease care in Indigenous communities in Canada: the FORGE AHEAD program protocol.

    Science.gov (United States)

    Naqshbandi Hayward, Mariam; Paquette-Warren, Jann; Harris, Stewart B

    2016-07-26

    Given the dramatic rise and impact of chronic diseases and gaps in care in Indigenous peoples in Canada, a shift from the dominant episodic and responsive healthcare model most common in First Nations communities to one that places emphasis on proactive prevention and chronic disease management is urgently needed. The Transformation of Indigenous Primary Healthcare Delivery (FORGE AHEAD) Program partners with 11 First Nations communities across six provinces in Canada to develop and evaluate community-driven quality improvement (QI) initiatives to enhance chronic disease care. FORGE AHEAD is a 5-year research program (2013-2017) that utilizes a pre-post mixed-methods observational design rooted in participatory research principles to work with communities in developing culturally relevant innovations and improved access to available services. This intensive program incorporates a series of 10 inter-related and progressive program activities designed to foster community-driven initiatives with type 2 diabetes mellitus as the action disease. Preparatory activities include a national community profile survey, best practice and policy literature review, and readiness tool development. Community-level intervention activities include community and clinical readiness consultations, development of a diabetes registry and surveillance system, and QI activities. With a focus on capacity building, all community-level activities are driven by trained community members who champion QI initiatives in their community. Program wrap-up activities include readiness tool validation, cost-analysis and process evaluation. In collaboration with Health Canada and the Aboriginal Diabetes Initiative, scale-up toolkits will be developed in order to build on lessons-learned, tools and methods, and to fuel sustainability and spread of successful innovations. The outcomes of this research program, its related cost and the subsequent policy recommendations, will have the potential to

  16. Design Expert® supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced behavioural performance in Parkinson’s disease

    Science.gov (United States)

    Kumar, Shobhit; Ali, Javed; Baboota, Sanjula

    2016-10-01

    Selegiline is a monoamine oxidase B (MAO-B) inhibitor and is used in the treatment of Parkinson’s disease. The main problem associated with its oral administration is its low oral bioavailability (10%) due to its poor aqueous solubility and extensive first pass metabolism. The aim of the present research work was to develop a nanoemulsion loaded with selegiline for direct nose-to-brain delivery for the better management of Parkinson’s disease. A quality by design (QbD) approach was used in a statistical multivariate method for the preparation and optimization of nanoemulsion. In this study, four independent variables were chosen, in which two were compositions and two were process variables, while droplet size, transmittance, zeta potential and drug release were selected as response variables. The optimized formulation was assessed for efficacy in Parkinson’s disease using behavioural studies, namely forced swimming, locomotor, catalepsy, muscle coordination, akinesia and bradykinesia or pole test in Wistar rats. The observed droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential and viscosity of selegiline nanoemulsion were found to be 61.43 ± 4.10 nm, 0.203 ± 0.005, 1.30 ± 0.01, 99.80 ± 0.04%, -34 mV and 31.85 ± 0.24 mPas respectively. Surface characterization studies demonstrated a spherical shape of nanoemulsion which showed 3.7 times enhancement in drug permeation as compared to drug suspension. The results of behaviour studies showed that treatment of haloperidol induced Parkinson’s disease in rats with selegiline nanoemulsion (administered intranasally) showed significant improvement in behavioural activities in comparison to orally administered drug. These findings demonstrate that nanoemulsion could be a promising new drug delivery carrier for intranasal delivery of selegiline in the treatment of Parkinson’s disease.

  17. A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-Cell immunogen shows enhanced immunogenicity in mice

    Directory of Open Access Journals (Sweden)

    Liu Xiangtao

    2011-02-01

    Full Text Available Abstract Background Foot-and-mouth disease (FMD is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must. Methods In the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE, and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine. Results Indirect immunofluorescence assay (IFA and indirect sandwich-ELISA (IS-ELISA showed both recombinant baculoviruses (with or without T-cell epitopes were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ. Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P P Conclusions These results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.

  18. Quality of life in patients receiving telemedicine enhanced chronic heart failure disease management: A meta-analysis.

    Science.gov (United States)

    Knox, Liam; Rahman, Rachel J; Beedie, Chris

    2017-08-01

    Background Previous reviews have investigated the effectiveness of telemedicine in the treatment of heart failure (HF). Dependent variables have included hospitalisations, mortality rates, disease knowledge and health costs. Few reviews, however, have examined the variable of health-related quality of life (QoL). Methods Randomised controlled trials comparing the delivery methods of any form of telemedicine with usual care for the provision of HF disease-management were identified via searches of all relevant databases and reference lists. Studies had to report a quantitative measure for mental, physical or overall QoL in order to be included. Results A total of 33 studies were identified. However, poor reporting of data resulted in the exclusion of seven, leaving 26 studies with 7066 participants. Three separate, random effects meta-analyses were conducted for mental, physical and overall QoL. Telemedicine was not significantly more effective than usual care on mental and physical QoL (standardised mean difference (SMD) 0.03, (95% confidence interval (CI) -0.05-0.12), p = 0.45 and SMD 0.24, (95% CI -0.08-0.56), p = 0.14, respectively). However, when compared to usual care, telemedicine was associated with a small significant increase in overall QoL (SMD 0.23, (95% CI 0.09-0.37), p = 0.001). Moderator analyses indicated that telemedicine delivered over a long-duration (≥52 weeks) and via telemonitoring was most beneficial. Conclusion Compared to usual care, telemedicine significantly increases overall QoL in patients receiving HF disease management. Statistically non-significant but nonetheless positive trends were also observed for physical QoL. These findings provide preliminary support for the use of telemedicine in the management of heart failure without jeopardising patient well-being.

  19. Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Yongming Pan

    2018-03-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia characterized by aggregation of amyloid β (Aβ and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ, a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC and low density lipoprotein-cholesterol (LDL-C, and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of β-site APP cleaving enzyme-1 (BACE1 and receptor for advanced glycation end products (RAGE, and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1 and insulin degrading enzyme (IDE. In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD.

  20. The Wheat Bax Inhibitor-1 Protein Interacts with an Aquaporin TaPIP1 and Enhances Disease Resistance in Arabidopsis

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    Pan-Pan Lu

    2018-01-01

    Full Text Available Bax inhibitor-1 (BI-1 is an endoplasmic reticulum (ER-resident cell death suppressor evolutionarily conserved in eukaryotes. The ability of BI-1 to inhibit the biotic and abiotic stresses have been well-studied in Arabidopsis, while the functions of wheat BI-1 are largely unknown. In this study, the wheat BI-1 gene TaBI-1.1 was isolated by an RNA-seq analysis of Fusarium graminearum (Fg-treated wheat. TaBI-1.1 expression was induced by a salicylic acid (SA treatment and down-regulated by an abscisic acid (ABA treatment. Based on β-glucuronidase (GUS staining, TaBI-1.1 was expressed in mature leaves and roots but not in the hypocotyl or young leaves. Constitutive expression of TaBI-1.1 in Arabidopsis enhanced its resistance to Pseudomonas syringae pv. Tomato (Pst DC3000 infection and induced SA-related gene expression. Additionally, TaBI-1.1 transgenic Arabidopsis exhibited an alleviation of damage caused by high concentrations of SA and decreased the sensitivity to ABA. Consistent with the phenotype, the RNA-seq analysis of 35S::TaBI-1.1 and Col-0 plants showed that TaBI-1.1 was involved in biotic stresses. These results suggested that TaBI-1.1 positively regulates SA signals and plays important roles in the response to biotic stresses. In addition, TaBI-1.1 interacted with the aquaporin TaPIP1, and both them were localized to ER membrane. Furthermore, we demonstrated that TaPIP1 was up-regulated by SA treatment and TaPIP1 transgenic Arabidopsis enhanced the resistance to Pst DC3000 infection. Thus, the interaction between TaBI-1.1 and TaPIP1 on the ER membrane probably occurs in response to SA signals and defense response.

  1. Therapeutic effects of remediating autophagy failure in a mouse model of Alzheimer disease by enhancing lysosomal proteolysis.

    Science.gov (United States)

    Yang, Dun-Sheng; Stavrides, Philip; Mohan, Panaiyur S; Kaushik, Susmita; Kumar, Asok; Ohno, Masuo; Schmidt, Stephen D; Wesson, Daniel W; Bandyopadhyay, Urmi; Jiang, Ying; Pawlik, Monika; Peterhoff, Corrinne M; Yang, Austin J; Wilson, Donald A; St George-Hyslop, Peter; Westaway, David; Mathews, Paul M; Levy, Efrat; Cuervo, Ana M; Nixon, Ralph A

    2011-07-01

    The extensive autophagic-lysosomal pathology in Alzheimer disease (AD) brain has revealed a major defect: in the proteolytic clearance of autophagy substrates. Autophagy failure contributes on several levels to AD pathogenesis and has become an important therapeutic target for AD and other neurodegenerative diseases. We recently observed broad therapeutic effects of stimulating autophagic-lysosomal proteolysis in the TgCRND8 mouse model of AD that exhibits defective proteolytic clearance of autophagic substrates, robust intralysosomal amyloid-β peptide (Aβ) accumulation, extracellular β-amyloid deposition and cognitive deficits. By genetically deleting the lysosomal cysteine protease inhibitor, cystatin B (CstB), to selectively restore depressed cathepsin activities, we substantially cleared Aβ, ubiquitinated proteins and other autophagic substrates from autolysosomes/lysosomes and rescued autophagic-lysosomal pathology, as well as reduced total Aβ40/42 levels and extracellular amyloid deposition, highlighting the underappreciated importance of the lysosomal system for Aβ clearance. Most importantly, lysosomal remediation prevented the marked learning and memory deficits in TgCRND8 mice. Our findings underscore the pathogenic significance of autophagic-lysosomal dysfunction in AD and demonstrate the value of reversing this dysfunction as an innovative therapeautic strategy for AD.

  2. Enhanced Sensitivity of Gas Sensor Based on Poly(3-hexylthiophene Thin-Film Transistors for Disease Diagnosis and Environment Monitoring

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    Marco R. Cavallari

    2015-04-01

    Full Text Available Electronic devices based on organic thin-film transistors (OTFT have the potential to supply the demand for portable and low-cost gadgets, mainly as sensors for in situ disease diagnosis and environment monitoring. For that reason, poly(3-hexylthiophene (P3HT as the active layer in the widely-used bottom-gate/bottom-contact OTFT structure was deposited over highly-doped silicon substrates covered with thermally-grown oxide to detect vapor-phase compounds. A ten-fold organochloride and ammonia sensitivity compared to bare sensors corroborated the application of this semiconducting polymer in sensors. Furthermore, P3HT TFTs presented approximately three-order higher normalized sensitivity than any chemical sensor addressed herein. The results demonstrate that while TFTs respond linearly at the lowest concentration values herein, chemical sensors present such an operating regime mostly above 2000 ppm. Simultaneous alteration of charge carrier mobility and threshold voltage is responsible for pushing the detection limit down to units of ppm of ammonia, as well as tens of ppm of alcohol or ketones. Nevertheless, P3HT transistors and chemical sensors could compose an electronic nose operated at room temperature for a wide range concentration evaluation (1–10,000 ppm of gaseous analytes. Targeted analytes include not only biomarkers for diseases, such as uremia, cirrhosis, lung cancer and diabetes, but also gases for environment monitoring in food, cosmetic and microelectronics industries.

  3. Cardiac Rehabilitation for Patients With Coronary Artery Disease: A Practical Guide to Enhance Patient Outcomes Through Continuity of Care

    Directory of Open Access Journals (Sweden)

    Catherine Giuliano

    2017-06-01

    Full Text Available Coronary artery disease (CAD is a leading cause of disease burden worldwide. Referral to cardiac rehabilitation (CR is a class I recommendation for all patients with CAD based on findings that participation can reduce cardiovascular and all-cause mortality, as well as improve functional capacity and quality of life. However, programme uptake remains low, systematic progression through the traditional CR phases is often lacking, and communication between health care providers is frequently suboptimal, resulting in fragmented care. Only 30% to 50% of eligible patients are typically referred to outpatient CR and fewer still complete the programme. In contemporary models of CR, patients are no longer treated by a single practitioner, but rather by an array of health professionals, across multiples specialities and health care settings. The risk of fragmented care in CR may be great, and a concerted approach is required to achieve continuity and optimise patient outcomes. ‘Continuity of care’ has been described as the delivery of services in a coherent, logical, and timely fashion and which entails 3 specific domains: informational, management, and relational continuity. This is examined in the context of CR.

  4. Building Infectious Disease Research Programs to Promote Security and Enhance Collaborations with Countries of the Former Soviet Union.

    Science.gov (United States)

    Bartholomew, James C; Pearson, Andrew D; Stenseth, Nils Chr; LeDuc, James W; Hirschberg, David L; Colwell, Rita R

    2015-01-01

    Addressing the threat of infectious diseases, whether natural, the results of a laboratory accident, or a deliberate act of bioterrorism, requires no corner of the world be ignored. The mobility of infectious agents and their rapid adaptability, whether to climate change or socioeconomic drivers or both, demand the science employed to understand these processes be advanced and tailored to a country or a region, but with a global vision. In many parts of the world, largely because of economic struggles, scientific capacity has not kept pace with the need to accomplish this goal and has left these regions and hence the world vulnerable to infectious disease outbreaks. To build scientific capability in a developing region requires cooperation and participation of experienced international scientists who understand the issues and are committed to educate the next generations of young investigators in the region. These efforts need to be coupled with the understanding and resolve of local governments and international agencies to promote an aggressive science agenda. International collaborative scientific investigation of infectious diseases not only adds significantly to scientific knowledge, but it promotes health security, international trust, and long-term economic benefit to the region involved. This premise is based on the observation that the most powerful human inspiration is that which brings peoples together to work on and solve important global challenges. The republics of the former Soviet Union provide a valuable case study for the need to rebuild scientific capacity as they are located at the crossroads where many of the world's great epidemics began. The scientific infrastructure and disease surveillance capabilities of the region suffered significant decline after the breakup of the Soviet Union. The U.S. Cooperative Threat Reduction (CTR) Program, a part of the U.S. Department of Defense, together with partner countries, have worked diligently to

  5. Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer's disease.

    Science.gov (United States)

    Simpkins, J W; Green, P S; Gridley, K E; Singh, M; de Fiebre, N C; Rajakumar, G

    1997-09-22

    Recent evidence supports a role for estrogens in both normal neural development and neuronal maintenance throughout life. Women spend 25-33% of their life in an estrogen-deprived state and retrospective studies have shown an inverse correlation between dose and duration of estrogen replacement therapy (ERT) and incidence of Alzheimer's disease (AD), suggesting a role for estrogen in the prevention and/or treatment of neurodegenerative diseases. To explore these observations further, an animal model was developed using ovariectomy (OVX) and ovariectomy with estradiol replacement (E2) in female Sprague-Dawley rats to mimic postmenopausal changes. Using an active-avoidance paradigm and a spatial memory task, the effects of estrogen deprivation were tested on memory-related behaviors. OVX caused a decline in avoidance behavior, and estrogen replacement normalized the response. In the Morris water task of spatial memory, OVX animals showed normal spatial learning but were deficient in spatial memory, an effect that was prevented by estrogen treatment. Together these data indicate that OVX in rats results in an estrogen-reversible impairment of learning/memory behavior. Because a plethora of information has been generated that links decline in memory-related behavior to dysfunction of cholinergic neurons, the effects of estrogens on cholinergic neurons were tested. We demonstrated that OVX causes a decrease in high affinity choline uptake and choline acetyltransferase activity in the hippocampus and frontal cortex; ERT reverses this effect. Further, we showed that estrogens promote the expression of mRNA for brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), 2 neurotrophic substances that have been shown to ameliorate the effects of age and injury on cholinergic neurons. Tissue culture models were used to evaluate whether estrogen treatment increases the survival of neurons when exposed to a variety of insults. 17-beta-Estradiol (beta-E2) protects

  6. Prediction of presence of kidney disease in a general patient population undergoing intravenous iodinated contrast enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Moos, Shira I.; Stoker, Jaap; Nagan, Gajenthiran; Weijert, Roderick S. de; Vemde, David N.H. van; Bipat, Shandra [Academic Medical Center, University of Amsterdam, Department of Radiology, G1-215, Amsterdam (Netherlands)

    2014-06-15

    To assess which risk factors can be used to reduce superfluous estimated glomerular filtration rate (eGFR) measurements before intravenous contrast medium administration. In consecutive patients, all decreased eGFR risk factors were assessed: diabetes mellitus (DM), history of urologic/nephrologic disease (HUND), nephrotoxic medication, cardiovascular disease, hypertension, age > 60 years, anaemia, malignancy and multiple myeloma/M. Waldenstroem. We studied four models: (1) all risk factors, (2) DM, HUND, hypertension, age > 60 years; (3) DM, HUND, cardiovascular disease, hypertension; (4) DM, HUND, age > 75 years and congestive heart failure. For each model, association with eGFR < 60 ml/min/1.73 m{sup 2} or eGFR < 45 ml/min/1.73 m{sup 2} was studied. A total of 998 patients, mean age 59.94 years were included; 112 with eGFR < 60 ml/min/1.73 m{sup 2} and 30 with eGFR < 45 ml/min/1.73 m{sup 2}. Model 1 detected 816 patients: 108 with eGFR < 60 ml/min/1.73 m{sup 2} and all 30 with eGFR < 45 ml/min/1.73 m{sup 2}. Model 2 detected 745 patients: 108 with eGFR < 60 ml/min/1.73 m{sup 2} and all 30 with eGFR < 45 ml/min/1.73 m{sup 2}. Model 3 detected 622 patients: 100 with eGFR < 60 ml/min/1.73 m{sup 2} and all 30 with eGFR < 45 ml/min/1.73 m{sup 2}. Model 4 detected 440 patients: 86 with eGFR < 60 ml/min/1.73 m{sup 2} and all 30 with eGFR < 45 ml/min/1.73 m{sup 2}. Associations were significant (p < 0.001). Model 4 is most effective, resulting in the lowest proportion of superfluous eGFR measurements while detecting all patients with eGFR < 45 ml/min/1.73 m{sup 2} and most with eGFR < 60 ml/min/1.73 m{sup 2}. (orig.)

  7. Comparative proteomic and metabolomic profiling of citrus fruit with enhancement of disease resistance by postharvest heat treatment.

    Science.gov (United States)

    Yun, Ze; Gao, Huijun; Liu, Ping; Liu, Shuzhen; Luo, Tao; Jin, Shuai; Xu, Qiang; Xu, Juan; Cheng, Yunjiang; Deng, Xiuxin

    2013-03-16

    From field harvest to the consumer's table, fresh citrus fruit spends a considerable amount of time in shipment and storage. During these processes, physiological disorders and pathological diseases are the main causes of fruit loss. Heat treatment (HT) has been widely used to maintain fruit quality during postharvest storage; however, limited molecular information related to this treatment is currently available at a systemic biological level. Mature 'Kamei' Satsuma mandarin (Citrus unshiu Marc.) fruits were selected for exploring the disease resistance mechanisms induced by HT during postharvest storage. Proteomic analyses based on two-dimensional gel electrophoresis (2-DE), and metabolomic research based on gas chromatography coupled to mass spectrometry (GC-MS), and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS) were conducted. The results show resistance associated proteins were up-regulated in heat treated pericarp, such as beta-1, 3-glucanase, Class III chitinase, 17.7 kDa heat shock protein and low molecular weight heat-shock protein. Also, redox metabolism enzymes were down-regulated in heat treated pericarp, including isoflavone reductase, oxidoreductase and superoxide dismutase. Primary metabolic profiling revealed organic acids and amino acids were down-regulated in heat treated pericarp; but significant accumulation of metabolites, including tetradecanoic acid, oleic acid, ornithine, 2-keto-d-gluconic acid, succinic acid, turanose, sucrose, galactose, myo-inositol, glucose and fructose were detected. Noticeably, H2O2 content decreased, while, lignin content increased in heat treated pericarp compared to the control, which might increase fruit resistibility in response to external stress. Also, flavonoids, substances which are well-known to be effective in reducing external stress, were up-regulated in heat treated pericarp. This study provides a broad picture of differential accumulation of proteins and metabolites in

  8. Does integrative medicine enhance balance in aging adults? Proof of concept for the benefit of electroacupuncture therapy in Parkinson's disease.

    Science.gov (United States)

    Toosizadeh, Nima; Lei, Hong; Schwenk, Michael; Sherman, Scott J; Sternberg, Esther; Mohler, Jane; Najafi, Bijan

    2015-01-01

    Postural balance and potentially fall risk increases among older adults living with neurological diseases, especially Parkinson's disease (PD). Since conventional therapies such as levodopa or deep brain stimulation may fail to alleviate or may even worsen balance, interest is growing in evaluating alternative PD therapies. The purpose of the current study was to assess improvement in postural balance in PD patients following electroacupuncture (EA) as an alternative therapy. 15 aging adults (71.2 ± 6.3 years) with idiopathic PD and 44 healthy age-matched participants (74.6 ± 6.5 years) were recruited. The PD participants were randomly assigned (at a ratio of 2:1) to an intervention (n = 10) or to a control group (n = 5). The intervention group received a 30-min EA treatment on a weekly basis for 3 weeks, while the control group received a sham treatment. Outcomes were assessed at baseline and after the final therapy. Measurements included balance assessment, specifically the ratio of medial-lateral (ML) center-of-gravity (COG) sway to anterior-posterior (AP) sway (COGML/AP) and ankle/hip sway during eyes-open, eyes-closed, and eyes-open dual-task trials, the Unified Parkinson's Disease Rating Scale (UPDRS), as well as quality of life, concerns for fall, and pain questionnaires. No difference was observed for the assessed parameters between the intervention and the control group at baseline. After treatment, an improvement in balance performance was observed in the intervention group. Compared with the healthy population, PD patients prior to treatment had larger COGML/AP sway with more dependency on upper-body movements for maintaining balance. Following EA therapy, COGML/AP sway was reduced by 31% and ankle/hip sway increased by 46% in the different conditions (p = 0.02 for the dual-task condition). The clinical rating revealed an overall improvement (p fall status (67%) and rigidity (48%). Changes were small and nonsignificant in the controls (p > 0.29). This

  9. Behavior change theory, content and delivery of interventions to enhance adherence in chronic respiratory disease: A systematic review.

    Science.gov (United States)

    McCullough, Amanda R; Ryan, Crístín; Macindoe, Christopher; Yii, Nathan; Bradley, Judy M; O'Neill, Brenda; Elborn, J Stuart; Hughes, Carmel M

    2016-07-01

    We sought to describe the theory used to design treatment adherence interventions, the content delivered, and the mode of delivery of these interventions in chronic respiratory disease. We included randomized controlled trials of adherence interventions (compared to another intervention or control) in adults with chronic respiratory disease (8 databases searched; inception until March 2015). Two reviewers screened and extracted data: post-intervention adherence (measured objectively); behavior change theory, content (grouped into psychological, education and self-management/supportive, telemonitoring, shared decision-making); and delivery. "Effective" studies were those with p theories. Use of theory (n = 11,41%) was more common amongst effective interventions. Interventions were mainly educational, self-management or supportive interventions (n = 27,47%). They were commonly delivered by a doctor (n = 20,23%), in face-to-face (n = 48,70%), one-to-one (n = 45,78%) outpatient settings (n = 46,79%) across 2-5 sessions (n = 26,45%) for 1-3 months (n = 26,45%). Doctors delivered a lower proportion (n = 7,18% vs n = 13,28%) and pharmacists (n = 6,15% vs n = 1,2%) a higher proportion of effective than ineffective interventions. Risk of bias was high in >1 domain (n = 43, 93%) in most studies. Behavior change theory was more commonly used to design effective interventions. Few adherence interventions have been developed using theory, representing a gap between intervention design recommendations and research practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The Teamwork Study: enhancing the role of non-GP staff in chronic disease management in general practice.

    Science.gov (United States)

    Black, D A; Taggart, J; Jayasinghe, U W; Proudfoot, J; Crookes, P; Beilby, J; Powell-Davis, G; Wilson, L A; Harris, M F

    2013-01-01

    There is evidence for a team-based approach in the management of chronic disease in primary health care. However, the standard of care is variable, probably reflecting the limited organisational capacity of health services to provide the necessary structured and organised care for this group of patients. This study aimed to evaluate the impact of a structured intervention involving non-GP staff in GP practices on the quality of care for patients with diabetes or cardiovascular disease. A cluster randomised trial was undertaken across 60 GP practices. The intervention was implemented in 30 practices with staff and patients interviewed at baseline and at 12-15 months follow up. The change in team roles was evaluated using a questionnaire completed by practice staff. The quality of care was evaluated using the Patient Assessment of Chronic Illness Care questionnaire. We found that although the team roles of staff improved in the intervention practices and there were significant differences between practices, there was no significant difference between those in the intervention and control groups in patient-assessed quality of care after adjusting for baseline-level score and covariates at the 12-month follow up. Practice team roles were not significantly associated with change in Patient Assessment of Chronic Illness Care scores. Patients with multiple conditions were more likely to assess their quality of care to be better. Thus, although previous research has shown a cross-sectional association between team work and quality of care, we were unable to replicate these findings in the present study. These results may be indicative of insufficient time for organisational change to result in improved patient-assessed quality of care, or because non-GP staff roles were not sufficiently focussed on the aspects of care assessed. The findings provide important information for researchers when designing similar studies.

  11. Multi-immunoreaction-based dual-color capillary electrophoresis for enhanced diagnostic reliability of thyroid gland disease.

    Science.gov (United States)

    Woo, Nain; Kim, Su-Kang; Kang, Seong Ho

    2017-08-04

    Thyroid-stimulating hormone (TSH) secretion plays a critical role in regulating thyroid gland function and circulating thyroid hormones (i.e., thyroxine (T4) and triiodothyronine (T3)). A novel multi-immunoreaction-based dual-color capillary electrophoresis (CE) technique was investigated in this study to assess its reliability in diagnosing thyroid gland disease via simultaneous detection of TSH, T3, and T4 in a single run of CE. Compared to the conventional immunoreaction technique, multi-immunoreaction of biotinylated streptavidin antibodies increased the selectivity and sensitivity for individual hormones in human blood samples. Dual-color laser-induced fluorescence (LIF) detection-based CE performed in a running buffer of 25mM Na 2 B 4 O 7 -NaOH (pH 9.3) allowed for fast, simultaneous quantitative analysis of three target thyroid hormones using different excited wavelengths within 3.2min. This process had excellent sensitivity and detection limits of 0.05-5.32 fM. The results showed 1000-100,000 times higher detection sensitivity than previous methods. Method validation with enzyme linked immunosorbent assay for application with human blood samples showed that the CE method was not significantly different at the 98% confidence level. Therefore, the developed CE-LIF method has the advantages of high detection sensitivity, faster analysis time, and smaller sample amount compared to the conventional methods The combined multi-immunoreaction and dual-color CE-LIF method should have increased diagnostic reliability for thyroid gland disease compared to conventional methods based on its highly sensitive detection of thyroid hormones using a single injection and high-throughput screening. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Evaluation of diabetic peripheral arterial disease in lower limb using 3.0 T contrast-enhanced MR angiography with simultaneous calf compression

    International Nuclear Information System (INIS)

    Li Jie; Zhao Jungong; Zhu Yueqi; Li Minghua; Wang Jue; Qiao Ruihua

    2011-01-01

    Objective: To determine the value of 3.0 T contrast-enhanced MR angiography (CE-MRA) with simultaneous calf compression in demonstrating and diagnosing diabetic peripheral vascular disease. Methods: Sixth-one patients with type 2 diabetes mellitus complicating vascular disease of lower limb were enrolled in this study. The patients included 37 males and 24 females with a mean age of (70±7.65) years. The mean duration of disease was (11.6±6.0) years. The patients were randomly divided into compression group (n=31) and conventional group (n=30). CE-MRA with a 3.0 T MR unit was performed in all patients. During CE-MRA, calf compression with a cuff was simultaneously applied to patients of compression group. DSA, which was regarded as gold standard, was conducted within one week after the procedure. The quality of MRA images was separately evaluated by two radiologists, the results were compared between two groups. Results: Taking DSA findings as reference, the image quality of calf and foot in compression group was much better than that in conventional group (P 50% arterial stenosis or occlusion of leg the image in compression group was also better than that in conventional group (P<0.05). CE-MRA with simultaneous calf compression could significantly eliminate the overlapping venous shadow (P<0.05). Conclusion: The 3.0 T CE-MRA with simultaneous calf compression is a simple and practical technique, it can markedly improve the image quality as well as the diagnostic accuracy of peripheral vascular disease of lower limb in diabetic patients. (authors)

  13. Image quality and diagnostic accuracy of unenhanced SSFP MR angiography compared with conventional contrast-enhanced MR angiography for the assessment of thoracic aortic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Krishnam, Mayil S. [University of California, Cardiovascular and Thoracic Imaging, UCI Medical Center, Irvine, CA (United States); Tomasian, Anderanik; Malik, Sachin; Ruehm, Stefan G. [University of California at Los Angeles, Department of Radiological Sciences, Ronald Reagan Medical Center, Los Angeles, CA (United States); Desphande, Vibhas; Laub, Gerhard [Siemens Medical Solutions, Los Angeles, CA (United States)

    2010-06-15

    The purpose of this study was to determine the image quality and diagnostic accuracy of three-dimensional (3D) unenhanced steady state free precession (SSFP) magnetic resonance angiography (MRA) for the evaluation of thoracic aortic diseases. Fifty consecutive patients with known or suspected thoracic aortic disease underwent free-breathing ECG-gated unenhanced SSFP MRA with non-selective radiofrequency excitation and contrast-enhanced (CE) MRA of the thorax at 1.5 T. Two readers independently evaluated the two datasets for image quality in the aortic root, ascending aorta, aortic arch, descending aorta, and origins of supra-aortic arteries, and for abnormal findings. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined for both datasets. Sensitivity, specificity, and diagnostic accuracy of unenhanced SSFP MRA for the diagnosis of aortic abnormalities were determined. Abnormal aortic findings, including aneurysm (n = 47), coarctation (n = 14), dissection (n = 12), aortic graft (n = 6), intramural hematoma (n = 11), mural thrombus in the aortic arch (n = 1), and penetrating aortic ulcer (n = 9), were confidently detected on both datasets. Sensitivity, specificity, and diagnostic accuracy of SSFP MRA for the detection of aortic disease were 100% with CE-MRA serving as a reference standard. Image quality of the aortic root was significantly higher on SSFP MRA (P < 0.001) with no significant difference for other aortic segments (P > 0.05). SNR and CNR values were higher for all segments on SSFP MRA (P < 0.01). Our results suggest that free-breathing navigator-gated 3D SSFP MRA with non-selective radiofrequency excitation is a promising technique that provides high image quality and diagnostic accuracy for the assessment of thoracic aortic disease without the need for intravenous contrast material. (orig.)

  14. Transgenic wheat expressing Thinopyrum intermedium MYB transcription factor TiMYB2R-1 shows enhanced resistance to the take-all disease.

    Science.gov (United States)

    Liu, Xin; Yang, Lihua; Zhou, Xianyao; Zhou, Miaoping; Lu, Yan; Ma, Lingjian; Ma, Hongxiang; Zhang, Zengyan

    2013-05-01

    The disease take-all, caused by the fungus Gaeumannomyces graminis, is one of the most destructive root diseases of wheat worldwide. Breeding resistant cultivars is an effective way to protect wheat from take-all. However, little progress has been made in improving the disease resistance level in commercial wheat cultivars. MYB transcription factors play important roles in plant responses to environmental stresses. In this study, an R2R3-MYB gene in Thinopyrum intermedium, TiMYB2R-1, was cloned and characterized. The gene sequence includes two exons and an intron. The expression of TiMYB2R-1 was significantly induced following G. graminis infection. An in vitro DNA binding assay proved that TiMYB2R-1 protein could bind to the MYB-binding site cis-element ACI. Subcellular localization assays revealed that TiMYB2R-1 was localized in the nucleus. TiMYB2R-1 transgenic wheat plants were generated, characterized molecularly, and evaluated for take-all resistance. PCR and Southern blot analyses confirmed that TiMYB2R-1 was integrated into the genomes of three independent transgenic wheat lines by distinct patterns and the transgene was heritable. Reverse transcription-PCR and western blot analyses revealed that TiMYB2R-1 was highly expressed in the transgenic wheat lines. Based on disease response assessments for three successive generations, the significantly enhanced resistance to take-all was observed in the three TiMYB2R-1-overexpressing transgenic wheat lines. Furthermore, the transcript levels of at least six wheat defence-related genes were significantly elevated in the TiMYB2R-1 transgenic wheat lines. These results suggest that engineering and overexpression of TiMYB2R-1 may be used for improving take-all resistance of wheat and other cereal crops.

  15. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

    Directory of Open Access Journals (Sweden)

    Marina Kovalenko

    Full Text Available The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111 with mice carrying a conditional (floxed Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.

  16. Image quality and diagnostic accuracy of unenhanced SSFP MR angiography compared with conventional contrast-enhanced MR angiography for the assessment of thoracic aortic diseases

    International Nuclear Information System (INIS)

    Krishnam, Mayil S.; Tomasian, Anderanik; Malik, Sachin; Ruehm, Stefan G.; Desphande, Vibhas; Laub, Gerhard

    2010-01-01

    The purpose of this study was to determine the image quality and diagnostic accuracy of three-dimensional (3D) unenhanced steady state free precession (SSFP) magnetic resonance angiography (MRA) for the evaluation of thoracic aortic diseases. Fifty consecutive patients with known or suspected thoracic aortic disease underwent free-breathing ECG-gated unenhanced SSFP MRA with non-selective radiofrequency excitation and contrast-enhanced (CE) MRA of the thorax at 1.5 T. Two readers independently evaluated the two datasets for image quality in the aortic root, ascending aorta, aortic arch, descending aorta, and origins of supra-aortic arteries, and for abnormal findings. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined for both datasets. Sensitivity, specificity, and diagnostic accuracy of unenhanced SSFP MRA for the diagnosis of aortic abnormalities were determined. Abnormal aortic findings, including aneurysm (n = 47), coarctation (n = 14), dissection (n = 12), aortic graft (n = 6), intramural hematoma (n = 11), mural thrombus in the aortic arch (n = 1), and penetrating aortic ulcer (n = 9), were confidently detected on both datasets. Sensitivity, specificity, and diagnostic accuracy of SSFP MRA for the detection of aortic disease were 100% with CE-MRA serving as a reference standard. Image quality of the aortic root was significantly higher on SSFP MRA (P 0.05). SNR and CNR values were higher for all segments on SSFP MRA (P < 0.01). Our results suggest that free-breathing navigator-gated 3D SSFP MRA with non-selective radiofrequency excitation is a promising technique that provides high image quality and diagnostic accuracy for the assessment of thoracic aortic disease without the need for intravenous contrast material. (orig.)

  17. Enhanced biocontrol activity of Rhodotorula mucilaginosa cultured in media containing chitosan against postharvest diseases in strawberries: possible mechanisms underlying the effect.

    Science.gov (United States)

    Zhang, Hongyin; Ge, Lingling; Chen, Keping; Zhao, Lina; Zhang, Xiaoyun

    2014-05-07

    The effect of Rhodotorula mucilaginosa cultured in media containing chitosan on its antogonistic activity against postharvest diseases of strawberries and the possible mechanisms involved are discussed. Two-dimensional gel electrophoresis were applied in the analysis of the proteins of R. mucilaginosa in response to chitosan. Compared with the application of R. mucilaginosa alone, the biocontrol efficacy of the yeast combined with 0.5% chitosan was enhanced greatly, with significant increase in chitinase activity of antagonistic yeast, polyphenoloxidase, peroxidase, phenylalanine ammonia lyase, chitinase and β-1,3-glucanase activity, and with an inhibition of lipid peroxidation of strawberries. The population of R. mucilaginosa harvested from NYDB amended with chitosan at 0.5% increased rapidly in strawberry wounds compared with those harvested from NYDB without chitosan. In the cellular proteome, several differentially expressed proteins were identified, most of which were related to basic metabolism.

  18. Accuracy of the Enhanced Liver Fibrosis Test vs Fibrotest, Elastography and Indirect Markers in Detection of Advanced Fibrosis in Patients with Alcoholic Liver Disease

    DEFF Research Database (Denmark)

    Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang

    2018-01-01

    BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2......-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). METHODS: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal...... significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P=.521 and .004 for comparison with ELF). Adding a serum marker to transient elastography...

  19. Building Infectious Disease Research Programs to Promote Security and Enhance Collaborations with Countries of the Former Soviet Union

    Directory of Open Access Journals (Sweden)

    James C Bartholomew

    2015-11-01

    Full Text Available Addressing the threat of infectious diseases, whether natural, the results of a laboratory accident, or a deliberate act of bioterrorism, requires no corner of the world be ignored. The mobility of infectious agents and their rapid adaptability, whether to climate change or socioeconomic drivers or both, demand the science employed to understand these processes be advanced and tailored to a country or a region, but with a global vision. In many parts of the world scientific capacity has not kept pace with the need, and has left these regions and hence the world vulnerable to infectious disease outbreaks. To build scientific capability in a developing region requires cooperation and participation of experienced international scientists who understand the issues and are committed to solve the issues. The Republics Georgia, formerly part of the Soviet Union provides a valuable case study for the need to rebuild scientific capacity as they are located at the crossroads where many of the world’s great epidemics began. The U.S. Cooperative Threat Reduction (CTR Program together with the Georgian government, have worked diligently to improve the capabilities in this region to guard against the potential future risk from especially dangerous pathogens. This effort culminated in the construction of a modern containment laboratory, the Richard G. Lugar Center for Public Health Research in Tbilisi to house both especially dangerous pathogens as well as the research to be conducted on these agents. The need now is to utilize and sustain the investment made by CTR by establishing strong public and animal health science programs tailored to the needs of the region and the goals for which this investment was made. Here we provide the analysis and recommendations of an international panel of expert scientists to provide advice to the stakeholders on the scientific path for the future. The emphasis is on an implementation strategy for decision makers and

  20. Is dignity therapy feasible to enhance the end of life experience for people with motor neurone disease and their family carers?

    Directory of Open Access Journals (Sweden)

    Bentley Brenda

    2012-09-01

    Full Text Available Abstract Background Development of interventions that address psychosocial and existential distress in people with motor neurone disease (MND or that alleviate caregiver burden in MND family carers have often been suggested in the research literature. Dignity therapy, which was developed to reduce psychosocial and existential distress at the end of life, has been shown to benefit people dying of cancer and their families. These results may not be transferable to people with MND. The objectives of this study are to assess the feasibility, acceptability and potential effectiveness of dignity therapy to enhance the end of life experience for people with motor neurone disease and their family carers. Methods/design This is a cross-sectional study utilizing a single treatment group and a pre/post test design. The study population will comprise fifty people diagnosed with MND and their nominated family carers. Primarily quantitative outcomes will be gathered through measures assessed at baseline and at approximately one week after the intervention. Outcomes for participants include hopefulness, spirituality and dignity. Outcomes for family carers include perceived caregiver burden, hopefulness and anxiety/depression. Feedback and satisfaction with the intervention will be gathered through a questionnaire. Discussion This detailed research will explore if dignity therapy has the potential to enhance the end of life experience for people with MND and their family carers, and fill a gap for professionals who are called on to address the spiritual, existential and psychosocial needs of their MND patients and families. Trial registration ACTRN Trial Number: ACTRN12611000410954

  1. Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

    Science.gov (United States)

    Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

    2016-07-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells

  2. Comparative analysis of minimal residual disease detection by multiparameter flow cytometry and enhanced ASO RQ-PCR in multiple myeloma

    International Nuclear Information System (INIS)

    Silvennoinen, R; Lundan, T; Kairisto, V; Pelliniemi, T-T; Putkonen, M; Anttila, P; Huotari, V; Mäntymaa, P; Siitonen, S; Uotila, L; Penttilä, T-L; Juvonen, V; Selander, T; Remes, K

    2014-01-01

    Multiparameter flow cytometry (MFC) and allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) are the two most sensitive methods to detect minimal residual disease (MRD) in multiple myeloma (MM). We compared these methods in 129 paired post-therapy samples from 22 unselected, consecutive MM patients in complete/near complete remission. Appropriate immunophenotypic and ASO RQ-PCR-MRD targets could be detected and MRD analyses constructed for all patients. The high PCR coverage could be achieved by gradual widening of the primer sets used for clonality detection. In addition, for 13 (55%) of the patients, reverse orientation of the ASO primer and individual design of the TaqMan probe improved the sensitivity and specificity of ASO RQ-PCR analysis. A significant nonlinear correlation prevailed between MFC-MRD and PCR-MRD when both were positive. Discordance between the methods was found in 32 (35%) paired samples, which were negative by MFC-MRD, but positive by ASO RQ-PCR. The findings suggest that with the described technique, ASO RQ-PCR can be constructed for all patients with MM. ASO RQ-PCR is slightly more sensitive in MRD detection than 6−10-color flow cytometry. Owing to technical demands ASO RQ-PCR could be reserved for patients in immunophenotypic remission, especially in efficacy comparisons between different drugs and treatment modalities

  3. Plant Growth Enhancement, Disease Resistance, and Elemental Modulatory Effects of Plant Probiotic Endophytic Bacillus sp. Fcl1.

    Science.gov (United States)

    Jayakumar, Aswathy; Krishna, Arathy; Mohan, Mahesh; Nair, Indu C; Radhakrishnan, E K

    2018-04-13

    Endophytic bacteria have already been studied for their beneficial support to plants to manage both biotic and abiotic stress through an array of well-established mechanisms. They have either direct or indirect impact on mobilizing diverse nutrients and elements from soil to plants. However, detailed insight into the fine-tuning of plant elemental composition by associated microorganism is very limited. In this study, endophytic Bacillus Fcl1 characterized from the rhizome of Curcuma longa was found to have broad range of plant growth-promoting and biocontrol mechanisms. The organism was found to have indole acetic acid and 1-aminocyclopropane-1-carboxylate deaminase production properties along with nitrogen fixation. The Bacillus Fcl1 could also inhibit diverse phytopathogens as confirmed by dual culture and well diffusion. By LC-MS/MS analysis, chemical basis of its antifungal activity has been proved to be due to the production of iturin A and a blend of surfactin compounds. Moreover, the organism was found to induce both plant growth and disease resistance in vivo in model plant system. Because of these experimentally demonstrated multiple plant probiotic features, Bacillus Fcl1 was selected as a candidate organism to study its role in modulation of plant elemental composition. ICP-MS analysis of Bacillus Fcl1-treated plants provided insight into relation of bacterial interaction with elemental composition of plants.

  4. Accelerated Senescence and Enhanced Disease Resistance in Hybrid Chlorosis Lines Derived from Interspecific Crosses between Tetraploid Wheat and Aegilops tauschii

    Science.gov (United States)

    Tosa, Yukio; Yoshida, Kentaro; Park, Pyoyun; Takumi, Shigeo

    2015-01-01

    Hybrid chlorosis, a type of hybrid incompatibility, has frequently been reported in inter- and intraspecific crosses of allopolyploid wheat. In a previous study, we reported some types of growth abnormalities such as hybrid necrosis and observed hybrid chlorosis with mild or severe abnormalities in wheat triploids obtained in crosses between tetraploid wheat cultivar Langdon and four Ae. tauschii accessions and in their derived synthetic hexaploids. However, the molecular mechanisms underlying hybrid chlorosis are not well understood. Here, we compared cytology and gene expression in leaves to characterize the abnormal growth in wheat synthetics showing mild and severe chlorosis. In addition, we compared disease resistance to wheat blast fungus. In total 55 and 105 genes related to carbohydrate metabolism and 53 and 89 genes for defense responses were markedly up-regulated in the mild and severe chlorosis lines, respectively. Abnormal chloroplasts formed in the mesophyll cells before the leaves yellowed in the hybrid chlorosis lines. The plants with mild chlorosis showed increased resistance to wheat blast and powdery mildew fungi, although significant differences only in two, third internode length and maturation time, out of the examined agricultural traits were found between the wild type and plants showing mild chlorosis. These observations suggest that senescence might be accelerated in hybrid chlorosis lines of wheat synthetics. Moreover, in wheat synthetics showing mild chlorosis, the negative effects on biomass can be minimized, and they may show substantial fitness under pathogen-polluted conditions. PMID:25806790

  5. Accelerated senescence and enhanced disease resistance in hybrid chlorosis lines derived from interspecific crosses between tetraploid wheat and Aegilops tauschii.

    Directory of Open Access Journals (Sweden)

    Hiroki Nakano

    Full Text Available Hybrid chlorosis, a type of hybrid incompatibility, has frequently been reported in inter- and intraspecific crosses of allopolyploid wheat. In a previous study, we reported some types of growth abnormalities such as hybrid necrosis and observed hybrid chlorosis with mild or severe abnormalities in wheat triploids obtained in crosses between tetraploid wheat cultivar Langdon and four Ae. tauschii accessions and in their derived synthetic hexaploids. However, the molecular mechanisms underlying hybrid chlorosis are not well understood. Here, we compared cytology and gene expression in leaves to characterize the abnormal growth in wheat synthetics showing mild and severe chlorosis. In addition, we compared disease resistance to wheat blast fungus. In total 55 and 105 genes related to carbohydrate metabolism and 53 and 89 genes for defense responses were markedly up-regulated in the mild and severe chlorosis lines, respectively. Abnormal chloroplasts formed in the mesophyll cells before the leaves yellowed in the hybrid chlorosis lines. The plants with mild chlorosis showed increased resistance to wheat blast and powdery mildew fungi, although significant differences only in two, third internode length and maturation time, out of the examined agricultural traits were found between the wild type and plants showing mild chlorosis. These observations suggest that senescence might be accelerated in hybrid chlorosis lines of wheat synthetics. Moreover, in wheat synthetics showing mild chlorosis, the negative effects on biomass can be minimized, and they may show substantial fitness under pathogen-polluted conditions.

  6. Maraba MG1 Virus Enhances Natural Killer Cell Function via Conventional Dendritic Cells to Reduce Postoperative Metastatic Disease

    Science.gov (United States)

    Zhang, Jiqing; Tai, Lee-Hwa; Ilkow, Carolina S; Alkayyal, Almohanad A; Ananth, Abhirami A; de Souza, Christiano Tanese; Wang, Jiahu; Sahi, Shalini; Ly, Lundi; Lefebvre, Charles; Falls, Theresa J; Stephenson, Kyle B; Mahmoud, Ahmad B; Makrigiannis, Andrew P; Lichty, Brian D; Bell, John C; Stojdl, David F; Auer, Rebecca C

    2014-01-01

    This study characterizes the ability of novel oncolytic rhabdoviruses (Maraba MG1) to boost natural killer (NK) cell activity. Our results demonstrate that MG1 activates NK cells via direct infection and maturation of conventional dendritic cells. Using NK depletion and conventional dendritic cells ablation studies in vivo, we established that both are required for MG1 efficacy. We further explored the efficacy of attenuated MG1 (nonreplicating MG1-UV2min and single-cycle replicating MG1-Gless) and demonstrated that these viruses activate conventional dendritic cells, although to a lesser extent than live MG1. This translates to equivalent abilities to remove tumor metastases only at the highest viral doses of attenuated MG1. In tandem, we characterized the antitumor ability of NK cells following preoperative administration of live and attenuated MG1. Our results demonstrates that a similar level of NK activation and reduction in postoperative tumor metastases was achieved with equivalent high viral doses concluding that viral replication is important, but not necessary for NK activation. Biochemical characterization of a panel of UV-inactivated MG1 (2–120 minutes) revealed that intact viral particle and target cell recognition are essential for NK cell–mediated antitumor responses. These findings provide mechanistic insight and preclinical rationale for safe perioperative virotherapy to effectively reduce metastatic disease following cancer surgery. PMID:24695102

  7. Real-Time 12-Lead High-Frequency QRS Electrocardiography for Enhanced Detection of Myocardial Ischemia and Coronary Artery Disease

    Science.gov (United States)

    Schlegel, Todd T.; Kulecz, Walter B.; DePalma, Jude L.; Feiveson, Alan H.; Wilson, John S.; Rahman, M. Atiar; Bungo, Michael W.

    2004-01-01

    Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

  8. Rice Dwarf Virus P2 Protein Hijacks Auxin Signaling by Directly Targeting the Rice OsIAA10 Protein, Enhancing Viral Infection and Disease Development.

    Directory of Open Access Journals (Sweden)

    Lian Jin

    2016-09-01

    Full Text Available The phytohormone auxin plays critical roles in regulating myriads of plant growth and developmental processes. Microbe infection can disturb auxin signaling resulting in defects in these processes, but the underlying mechanisms are poorly understood. Auxin signaling begins with perception of auxin by a transient co-receptor complex consisting of an F-box transport inhibitor response 1/auxin signaling F-box (TIR1/AFB protein and an auxin/indole-3-acetic acid (Aux/IAA protein. Auxin binding to the co-receptor triggers ubiquitination and 26S proteasome degradation of the Aux/IAA proteins, leading to subsequent events, including expression of auxin-responsive genes. Here we report that Rice dwarf virus (RDV, a devastating pathogen of rice, causes disease symptoms including dwarfing, increased tiller number and short crown roots in infected rice as a result of reduced sensitivity to auxin signaling. The RDV capsid protein P2 binds OsIAA10, blocking the interaction between OsIAA10 and OsTIR1 and inhibiting 26S proteasome-mediated OsIAA10 degradation. Transgenic rice plants overexpressing wild-type or a dominant-negative (degradation-resistant mutant of OsIAA10 phenocopy RDV symptoms are more susceptible to RDV infection; however, knockdown of OsIAA10 enhances the resistance of rice to RDV infection. Our findings reveal a previously unknown mechanism of viral protein reprogramming of a key step in auxin signaling initiation that enhances viral infection and pathogenesis.

  9. Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2015-01-01

    Full Text Available Purpose. To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD using contrast-enhanced ultrasound (CEUS method. Materials and Methods. 79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA group and a high SUA group. Contrast-enhanced ultrasound (CEUS was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis. Results. Normal controls (NCs had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P<0.05. DKD patients with low urinary uric acid (UUA excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P<0.05. Conclusion. Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

  10. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? There Is Only One True Winner.

    Science.gov (United States)

    Halstead, Scott B

    2017-07-17

    The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1. It is also possible that chimeric structure does not present the correct virion conformation permitting the development of protective neutralizing antibodies. A premonitory signal shared by the Sanofi Pasteur and the Takeda vaccines was the failure of fully immunized subhuman primates to prevent low-level viremia and/or anamnestic antibody responses to live DENV challenge. The vaccine developed by the National Institute of Allergy and Infectious Diseases (National Institutes of Health [NIH]) has met virtually all of the goals needed to demonstrate preclinical efficacy and safety for humans. Each monovalent vaccine was comprehensively studied for reactogenicity and immunogenicity in human volunteers. Protective immunity in subjects receiving tetravalent candidate vaccines was evidenced by the fact that when vaccinated subjects were given further doses of vaccine or different strains of DENV the result was "solid immunity," a nonviremic and nonanamnestic immune response. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  11. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation

    Directory of Open Access Journals (Sweden)

    Niranjan Y. Sardesai

    2013-07-01

    Full Text Available Lassa virus (LASV causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC that expressed the LASV glycoprotein precursor gene (GPC. This plasmid was used to vaccinate guinea pigs (GPs using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6 with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.

  12. Influence of contrast-enhanced CT and MRI with or without SPIO particles on therapy and therapy costs for patients with focal liver disease

    International Nuclear Information System (INIS)

    Helmberger, T.; Gregor, M.; Holzknecht, N.; Scheidler, J.; Reiser, M.; Rau, H.

    2000-01-01

    Purpose: Evaluation of the diagnostic efficacy and cost-benefit of contrast enhanced CT (CT) and MRI pre- and post-SPIO-particles in focal hepatic disease with consideration of therapeutic outcome. Results: In 34/52 (65.4%) of the cases the correct diagnosis was primarily stated by CT (sensitivity [se.] 85.2%, specificity [sp.] 44.0%). In additional 10/52 of the cases unenhanced MRI (se. 91.4%, sp. 75.0%) enabled correct diagnoses, and in another 6 cases the diagnosis was established only by SPIO-MRI (se. 100%, sp. 86.7%). Considering the possible therapeutic recommendation arising from each modality, CT would have induced needless therapy costs of 191,042 DM, unenhanced MRI of 171,035 DM, and SPIO-MRI of 7,311 DM. In comparison to the real therapy costs of 221,873 DM, this would have corresponded to an unnecessary increase of therapy costs of 86.1%, 77.1%, and 3.3%, respectively. In two cases (91 hemangioma, 1 regenerative nodule) all modalities failed, causing unnecessary surgery in one patient. Discussion: In this problem-oriented scenario unenhanced and SPIO-enhanced MRI proved to be superior to CT regarding diagnostic efficacy. The cost-benefit resulted mainly due to preserving patients from unnecessary surgical procedures. (orig./AJ) [de

  13. Intranasal Delivery of Plasma and Platelet Growth Factors Using PRGF-Endoret System Enhances Neurogenesis in a Mouse Model of Alzheimer’s Disease

    Science.gov (United States)

    Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Antequera, Desiree; Padilla, Sabino; Orive, Gorka; Carro, Eva

    2013-01-01

    Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer’s disease (AD) induced by a combination of toxic amyloid-β peptide (Aβ) and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret), an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD. PMID:24069173

  14. Intranasal delivery of plasma and platelet growth factors using PRGF-Endoret system enhances neurogenesis in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Eduardo Anitua

    Full Text Available Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer's disease (AD induced by a combination of toxic amyloid-β peptide (Aβ and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret, an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1 mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU, doublecortin (DCX, and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD.

  15. Intranasal delivery of plasma and platelet growth factors using PRGF-Endoret system enhances neurogenesis in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Antequera, Desiree; Padilla, Sabino; Orive, Gorka; Carro, Eva

    2013-01-01

    Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer's disease (AD) induced by a combination of toxic amyloid-β peptide (Aβ) and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret), an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD.

  16. Visualization of endolymphatic hydrops in meniere's disease after single-dose intravenous gadolinium-based contrast medium. Timing of optimal enhancement

    International Nuclear Information System (INIS)

    Naganawa, Shinji; Yamazaki, Masahiro; Kawai, Hisashi; Bokura, Kiminori; Sone, Michihiko; Nakashima, Tsutomu

    2012-01-01

    Visualization of endolymphatic hydrops (EH) in patients with Meniere's disease (MD) is now possible by heavily T 2 -weighted 3-dimensional fluid-attenuated inversion recovery (h T 2 W-3D-FLAIR) obtained 4 hours after intravenous (IV) administration of single dose gadolinium-based contrast medium (GBCM). Although maximum enhancement has been reported 4 hours after contrast administration in healthy volunteers, the timing of optimal enhancement in patients with MD is not reported. We investigated if that optimal timing is earlier or later than 4 hours. We evaluated 10 consecutive patients with suspected MD whom we randomly divided into 2 groups. We obtained h T 2 W-3D-FLAIR before GBCM administration and 10 min, 3.5 hours, and 4 hours after GBCM administration in Group A and before and 10 min, 4 hours, and 4.5 hours after GBCM administration in Group B. We compared signal intensity ratio (SIR) values of the perilymph and pons between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B and evaluated grades of EH at 3.5 and 4 hours in Group A and at 4 and 4.5 hours in Group B. SIR values did not differ significantly between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B. However, SIR values at 4 hours were significantly higher in Group A than Group B. Grades of EH agreed between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B. The optimal timing of contrast enhancement in patients with suspected MD remains unclear, but evaluation of EH may be possible from 3.5 to 4.5 hours after contrast administration. (author)

  17. Comparison of gadofosveset-enhanced three-dimensional magnetic resonance angiography with digital subtraction angiography for lower-extremity peripheral arterial occlusive disease

    International Nuclear Information System (INIS)

    Grijalba, Fermin Urtasun; Esandi, Mercedes Ciriza

    2010-01-01

    Background: Minimally invasive imaging techniques are increasingly used for clinical decision making in patients with peripheral arterial occlusive disease (PAOD). Purpose: To assess whether gadofosveset-enhanced three-dimensional (3D) magnetic resonance (MR) angiography could replace digital subtraction angiography (DSA) for the evaluation of lower-extremity PAOD. Material and Methods: Thirty patients with symptomatic PAOD underwent prospectively both MR angiography and DSA. Gadofosveset-enhanced 3D MR angiography was performed on a 1.5T system equipped with a peripheral angio matrix coil. Four blinded observers independently analyzed MR angiograms and DSA images. The lower arterial vascular system was divided into three anatomic segments (aortoiliac, femoropopliteal, infrapopliteal) for review. The status of each segment was graded as normal, stenosis less than 50%, stenosis greater than 50%, or occluded and/or aneurismatic. Principal and secondary lesions were reported. Results: Although interobserver agreement for both was excellent, it was higher for DSA (?=0.92) than for MR angiography (?=0.86) for reporting the principal and secondary lesions in all segments. For different anatomic locations, the interobserver agreement of MR angiography and DSA was as follows: aortoiliac (?=0.93, k=0.95), femoropopliteal (?=0.86, k=0.90), and infrapopliteal (?=0.78, k=0.85). The lowest agreement was found for MR angiography on infrapopliteal segments (?=0.78). In four (13.3%) cases, MR angiography showed lesions that were not found by DSA. Five (16.6%) aneurysm cases, not observed by DSA, were shown by MR angiography. Conclusion: Gadofosveset-enhanced 3D MR angiography can be proposed for first-line imaging in the management of lower-limb PAOD patients and permits the selective use of DSA as a second-line examination when MR angiography fails or in an endovascular approach

  18. Noninvasive Differentiation between Hepatic Steatosis and Steatohepatitis with MR Imaging Enhanced with USPIOs in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study.

    Science.gov (United States)

    Smits, Loek P; Coolen, Bram F; Panno, Maria D; Runge, Jurgen H; Nijhof, Wouter H; Verheij, Joanne; Nieuwdorp, Max; Stoker, Jaap; Beuers, Ulrich H; Nederveen, Aart J; Stroes, Erik S

    2016-03-01

    To (a) study the optimal timing and dosing for ultrasmall superparamagnetic iron oxide particle (USPIO)-enhanced magnetic resonance (MR) imaging of the liver in nonalcoholic fatty liver disease, (b) evaluate whether hepatic USPIO uptake is decreased in nonalcoholic steatohepatitis (NASH), and (c) study the diagnostic accuracy of USPIO-enhanced MR imaging to distinguish between NASH and simple steatosis. This prospective study was approved by the local institutional review board, and informed consent was obtained from all patients. Quantitative R2* MR imaging of the liver was performed at baseline and 72 hours after USPIO administration in patients with biopsy-proven NASH (n = 13), hepatic steatosis without NASH (n = 11), and healthy control subjects (n = 9). The hepatic USPIO uptake in the liver was quantified by the difference in R2* (ΔR2*) between the contrast material-enhanced images and baseline images. Between-group differences in mean ΔR2* were tested with the Student t test, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristic curve. Patients with NASH had a significantly lower ΔR2* 72 hours after USPIO administration when compared with patients who had simple steatosis and healthy control subjects (mean ± standard deviation for patients with NASH, 37.0 sec(-1) ± 16.1; patients with simple steatosis, 61.0 sec(-1) ± 17.3; and healthy control subjects, 72.2 sec(-1) ± 22.0; P = .006 for NASH vs simple steatosis; P steatosis was 0.87 (95% confidence interval: 0.72, 1.00). This proof-of-concept study provides clues that hepatic USPIO uptake in patients with NASH is decreased and that USPIO MR imaging can be used to differentiate NASH from simple steatosis.

  19. Preclinical study of diagnostic performances of contrast-enhanced spectral mammography versus MRI for breast diseases in China.

    Science.gov (United States)

    Wang, Qingguo; Li, Kangan; Wang, Lihui; Zhang, Jianbing; Zhou, Zhiguo; Feng, Yan

    2016-01-01

    To evaluate diagnostic performances of CESM for breast diseases with comparison to breast MRI in China. Sixty-eight patients with 77 breast lesions underwent MR and CESM. Two radiologists interpreted either MRI or CESM images, separately and independently. BI-RADS 1-3 and BI-RADS 4-5 were classified into the suspicious benign and suspicious malignant groups. Diagnostic accuracy parameters were calculated. Receiver operating characteristic (ROC) curves were constructed for the two modalities. The agreement and correlation between maximum lesion diameter based on CESM and MRI, or CESM and pathology were analyzed. Diagnostic accuracy parameters for CESM were sensitivity 95.8 %, specificity 65.5 %, PPV 82.1 %, NPV 90.5 % and accuracy 84.4 %. The diagnostic accuracy parameters for breast MRI were sensitivity 93.8 %, specificity 82.8 %, PPV 88.2 %, NPV 92.3 %and accuracy 89.6 %. Area under the curve (AUC) of ROC was 0.96 for breast MRI and 0.88 for CESM. The Bland-Altman plots showed a mean difference of 0.7 mm with 95 % limits of agreement of 11.4 mm in tumor diameter measured using CESM and breast MRI. The differences of size measurement between CESM and breast MRI were significant, whereas no difference was observed between CESM and pathology as well as between breast MRI and pathology. The better correlation with pathological results was found in CESM than breast MRI. Our study demonstrates that CESM possesses better diagnostic performances than breast MRI in terms of diagnostic sensitivity and lesion size assessment. And CESM is a good alternative method of screening breast cancer in high-risk people.

  20. Distinct neural systems underlying reduced emotional enhancement for positive and negative stimuli in early Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Panagiota eMistridis

    2014-01-01

    Full Text Available Emotional information is typically better remembered than neutral content, and previous studies suggest that this effect is subserved particularly by the amygdala together with its interactions with the hippocampus. However, it is not known whether amygdala damage affects emotional memory performance at immediate and delayed recall, and whether its involvement is modulated by stimulus valence. Moreover, it is unclear to what extent more distributed neocortical regions involved in e.g. autobiographical memory, also contribute to emotional processing. We investigated these questions in a group of patients with Alzheimer’s disease (AD, which affects the amygdala, hippocampus and neocortical regions. Healthy controls (n = 14, patients with AD (n = 15 and its putative prodrome amnestic mild cognitive impairment (n = 11 completed a memory task consisting of immediate and delayed free recall of a list of positive, negative and neutral words. Memory performance was related to brain integrity in region of interest and whole-brain voxel-based morphometry analyses. In the brain-behavioral analyses, the left amygdala volume predicted the immediate recall of both positive and negative material, whereas at delay, left and right amygdala volumes were associated with performance with positive and negative words, respectively. Whole-brain analyses revealed additional associations between left angular gyrus integrity and the immediate recall of positive words as well as between the orbitofrontal cortex and the delayed recall of negative words. These results indicate that emotional memory impairments in AD may be underpinned by damage to regions implicated in emotional processing as well as frontoparietal regions, which may exert their influence via autobiographical memories and organizational strategies.

  1. Improving the image quality of contrast-enhanced MR angiography by automated image registration: A prospective study in peripheral arterial disease of the lower extremities

    International Nuclear Information System (INIS)

    Menke, Jan

    2010-01-01

    Objective: If a patient has moved during digital subtraction angiography (DSA), manual pixel shift can improve the image quality. This study investigated whether such image registration can also improve the quality of contrast-enhanced magnetic resonance angiography (MRA) in patients with peripheral arterial disease of the lower extremities. Materials and methods: 404 leg MRAs of patients likely to have peripheral artery disease were included in this prospective study. The standard non-registered MRAs were compared to automatically linear, affine and warp registered MRAs by four image quality parameters, including the vessel detection probability (VDP) in maximum intensity projection (MIP) images and contrast-to-noise ratios (CNR). The different registration types were compared by analysis of variance. Results: All studied image quality parameters showed similar trends. Generally, registration improved the leg MRA quality significantly (P < 0.05). The 12% of lower legs with a body shift of 1 mm or more showed the highest gain in image quality when using linear registration instead of no registration, with an average VDP gain of 20-49%. Warp registration improved the image quality slightly further. Conclusion: Automated image registration can improve the MRA image quality especially in the lower legs, which is comparable to the effect of pixel shift in DSA.

  2. Biomarker research for moyamoya disease in cerebrospinal fluid using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Maruwaka, Mikio; Yoshikawa, Kazuhiro; Okamoto, Sho; Araki, Yoshio; Sumitomo, Masaki; Kawamura, Akino; Yokoyama, Kinya; Wakabayashi, Toshihiko

    2015-01-01

    Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by steno-occlusive change in bilateral internal carotid arteries with unknown etiology. To discover biomarker candidates in cerebrospinal fluid from MMD patients, proteome analysis was performed by the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Three peptides, 4473Da, 4475Da, and 6253Da, were significantly elevated in MMD group. A positive correlation between 4473Da peptide and postoperative angiogenesis was determined. Twenty MMD patients were enrolled in this pilot study, including 11 pediatric cases less than 18 years of age (mean age, 8.67 years) and 9 adult MMD patients (mean age, 38.1 years). This study also includes 17 control cases with the mean age of 27.9 years old. In conclusion, 4473Da peptide is supposed to be a reliable biomarker of MMD. 4473Da peptide showed higher intensity peaks especially in younger MMD patients, and it was proved to be highly related to postoperative angiogenesis. Further study is needed to show how 4473Da peptide is involved with the etiology and the onset of MMD. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Effect of simultaneous application of postural techniques and expiratory muscle strength training on the enhancement of the swallowing function of patients with dysphagia caused by parkinson's disease.

    Science.gov (United States)

    Byeon, Haewon

    2016-06-01

    [Purpose] This study aimed to investigate the effect of simultaneous application of postural techniques and expiratory muscle strength training on the enhancement of the swallowing function of patients with dysphagia caused by Parkinson's disease. [Subjects and Methods] The subjects of this study were 18 patients who received simultaneous application of postural techniques and expiratory muscle strength training and 15 patients who received expiratory muscle strength training only. Postural techniques were conducted in the order of chin tucking, head rotation, head tilting, bending head back, and lying down, while expiratory muscle strength training was conducted at a resistance level of about 70% of the maximal expiratory pressure. Swallowing recovery was assessed by using the Functional Dysphagia Scale based on videofluoroscopic studies. [Results] The mean value obtained in the videofluoroscopic studies for both groups decreased after the treatment. In the postural techniques plus expiratory muscle strength training group, the decrease was significantly greater than that in the expiratory muscle strength training-only group. [Conclusion] The results imply that simultaneous performance of postural techniques and expiratory muscle strength training is more effective than expiratory muscle strength training alone when applied in the swallowing rehabilitation for patients with dysphagia caused by Parkinson's disease.

  4. Harnessing Diversity in Wheat to Enhance Grain Yield, Climate Resilience, Disease and Insect Pest Resistance and Nutrition Through Conventional and Modern Breeding Approaches

    Science.gov (United States)

    Mondal, Suchismita; Rutkoski, Jessica E.; Velu, Govindan; Singh, Pawan K.; Crespo-Herrera, Leonardo A.; Guzmán, Carlos; Bhavani, Sridhar; Lan, Caixia; He, Xinyao; Singh, Ravi P.

    2016-01-01

    Current trends in population growth and consumption patterns continue to increase the demand for wheat, a key cereal for global food security. Further, multiple abiotic challenges due to climate change and evolving pathogen and pests pose a major concern for increasing wheat production globally. Triticeae species comprising of primary, secondary, and tertiary gene pools represent a rich source of genetic diversity in wheat. The conventional breeding strategies of direct hybridization, backcrossing and selection have successfully introgressed a number of desirable traits associated with grain yield, adaptation to abiotic stresses, disease resistance, and bio-fortification of wheat varieties. However, it is time consuming to incorporate genes conferring tolerance/resistance to multiple stresses in a single wheat variety by conventional approaches due to limitations in screening methods and the lower probabilities of combining desirable alleles. Efforts on developing innovative breeding strategies, novel tools and utilizing genetic diversity for new genes/alleles are essential to improve productivity, reduce vulnerability to diseases and pests and enhance nutritional quality. New technologies of high-throughput phenotyping, genome sequencing and genomic selection are promising approaches to maximize progeny screening and selection to accelerate the genetic gains in breeding more productive varieties. Use of cisgenic techniques to transfer beneficial alleles and their combinations within related species also offer great promise especially to achieve durable rust resistance. PMID:27458472

  5. Combined evaluation of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the identification of viable myocardium in patients with chronic coronary artery disease

    International Nuclear Information System (INIS)

    Pace, L.; Cuocolo, A.; Salvatore, M.; Perrone-Filardi, P.; Prastaro, M.; Vezzuto, P.; Crisci, T.; Dellegrottaglie, S.; Piscione, F.; Chiariello, M.; Mainenti, P.P.; Varrone, A.

    1998-01-01

    The purpose of this study was to evaluate whether combined evaluation by discriminant analysis of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the accuracy in identifying viable myocardium in patients with chronic coronary artery disease. Rest-redistribution 201 Tl has high sensitivity but low specificity in identifying viable myocardium, while the opposite is true for low-dose dobutamine echocardiography. Forty-six patients underwent low-dose dobutamine echocardiography and rest-redistribution 201 Tl tomography on the same day. Rest echocardiography was repeated at least 30 days (mean 40±20) after myocardial revascularization. Discriminant analysis was applied to the results of 201 Tl tomography and dobutamine echocardiography to classify a/dyskinetic segments as viable or non-viable. In 92 a/dyskinetic segments that were revascularized, rest-redistribution 201 Tl tomography yielded an accuracy of 75%, while the accuracy of dobutamine echocardiography was 70% (P 201 Tl imaging are useful and complementary techniques for identifying viable myocardium in patients with chronic coronary artery disease. Combined evaluation by discriminant analysis significantly improves accuracy, although the cost-effectiveness of such an approach remains to be determined. (orig.)

  6. Application of Cavity Enhanced Absorption Spectroscopy to the Detection of Nitric Oxide, Carbonyl Sulphide, and Ethane--Breath Biomarkers of Serious Diseases.

    Science.gov (United States)

    Wojtas, Jacek

    2015-06-17

    The paper presents one of the laser absorption spectroscopy techniques as an effective tool for sensitive analysis of trace gas species in human breath. Characterization of nitric oxide, carbonyl sulphide and ethane, and the selection of their absorption lines are described. Experiments with some biomarkers showed that detection of pathogenic changes at the molecular level is possible using this technique. Thanks to cavity enhanced spectroscopy application, detection limits at the ppb-level and short measurements time (laser and a tunable laser system consisting of an optical parametric oscillator and difference frequency generator. Setup using the first source provided a detection limit of 30 ppb for nitric oxide and 250 ppb for carbonyl sulphide. During experiments employing a second laser, detection limits of 0.9 ppb and 0.3 ppb were obtained for carbonyl sulphide and ethane, respectively. The conducted experiments show that this type of diagnosis would significantly increase chances for effective therapy of some diseases. Additionally, it offers non-invasive and real time measurements, high sensitivity and selectivity as well as minimizing discomfort for patients. For that reason, such sensors can be used in screening for early detection of serious diseases.

  7. Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses

    Directory of Open Access Journals (Sweden)

    Lannes Nils

    2012-08-01

    Full Text Available Abstract Foot-and-mouth disease virus (FMDV is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN by plasmacytoid dendritic cells (pDC. The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses.

  8. Enhancing the Capacity of Policy-Makers to Develop Evidence-Informed Policy Brief on Infectious Diseases of Poverty in Nigeria

    Directory of Open Access Journals (Sweden)

    Chigozie Jesse Uneke

    2015-09-01

    Full Text Available Background The lack of effective use of research evidence in policy-making is a major challenge in most low- and middle-income countries (LMICs. There is need to package research data into effective policy tools that will help policy-makers to make evidence-informed policy regarding infectious diseases of poverty (IDP. The objective of this study was to assess the usefulness of training workshops and mentoring to enhance the capacity of Nigerian health policy-makers to develop evidence-informed policy brief on the control of IDP. Methods A modified “before and after” intervention study design was used in which outcomes were measured on the target participants both before the intervention is implemented and after. A 4-point Likert scale according to the degree of adequacy; 1 = “grossly inadequate,” 4 = “very adequate” was employed. The main parameter measured was participants’ perceptions of their own knowledge/understanding. This study was conducted at subnational level and the participants were the career health policy-makers drawn from Ebonyi State in the South-Eastern Nigeria. A oneday evidence-to-policy workshop was organized to enhance the participants’ capacity to develop evidence-informed policy brief on IDP in Ebonyi State. Topics covered included collaborative initiative; preparation and use of policy briefs; policy dialogue; ethics in health policy-making; and health policy and politics. Results The preworkshop mean of knowledge and capacity ranged from 2.49-3.03, while the postworkshop mean ranged from 3.42–3.78 on 4-point scale. The percentage increase in mean of knowledge and capacity at the end of the workshop ranged from 20.10%–45%. Participants were divided into 3 IDP mentorship groups (malaria, schistosomiasis, lymphatic filariasis [LF] and were mentored to identify potential policy options/recommendations for control of the diseases for the policy briefs. These policy options were subjected to research

  9. Enhancing the Capacity of Policy-Makers to Develop Evidence-Informed Policy Brief on Infectious Diseases of Poverty in Nigeria

    Science.gov (United States)

    Uneke, Chigozie Jesse; Ezeoha, Abel Ebeh; Uro-Chukwu, Henry; Ezeonu, Chinonyelum Thecla; Ogbu, Ogbonnaya; Onwe, Friday; Edoga, Chima

    2015-01-01

    Background: The lack of effective use of research evidence in policy-making is a major challenge in most low- and middle-income countries (LMICs). There is need to package research data into effective policy tools that will help policy-makers to make evidence-informed policy regarding infectious diseases of poverty (IDP). The objective of this study was to assess the usefulness of training workshops and mentoring to enhance the capacity of Nigerian health policy-makers to develop evidence-informed policy brief on the control of IDP. Methods: A modified "before and after" intervention study design was used in which outcomes were measured on the target participants both before the intervention is implemented and after. A 4-point Likert scale according to the degree of adequacy; 1 = "grossly inadequate," 4 = "very adequate" was employed. The main parameter measured was participants’ perceptions of their own knowledge/understanding. This study was conducted at subnational level and the participants were the career health policy-makers drawn from Ebonyi State in the South-Eastern Nigeria. A one-day evidence-to-policy workshop was organized to enhance the participants’ capacity to develop evidence-informed policy brief on IDP in Ebonyi State. Topics covered included collaborative initiative; preparation and use of policy briefs; policy dialogue; ethics in health policy-making; and health policy and politics. Results: The preworkshop mean of knowledge and capacity ranged from 2.49-3.03, while the postworkshop mean ranged from 3.42–3.78 on 4-point scale. The percentage increase in mean of knowledge and capacity at the end of the workshop ranged from 20.10%–45%. Participants were divided into 3 IDP mentorship groups (malaria, schistosomiasis, lymphatic filariasis [LF]) and were mentored to identify potential policy options/recommendations for control of the diseases for the policy briefs. These policy options were subjected to research evidence synthesis by each

  10. Quantitative comparison of 2D and 3D late gadolinium enhancement MR imaging in patients with Fabry disease and hypertrophic cardiomyopathy.

    Science.gov (United States)

    Morsbach, F; Gordic, S; Gruner, C; Niemann, M; Goetti, R; Gotschy, A; Kozerke, S; Alkadhi, H; Manka, R

    2016-08-15

    This study aims to determine whether the quantification of myocardial fibrosis in patients with Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) using a late gadolinium enhancement (LGE) singlebreath-hold three-dimensional (3D) inversion recovery magnetic resonance (MR) imaging sequence is comparable with a clinically established two-dimensional (2D) multi-breath-hold sequence. In this retrospective, IRB-approved study, 40 consecutive patients (18 male; mean age 50±17years) with Fabry disease (n=18) and HCM (n=22) underwent MR imaging at 1.5T. Spatial resolution was the same for 3D and 2D images (field-of-view, 350×350mm(2); in-plane-resolution, 1.2×1.2mm(2); section-thickness, 8mm). Datasets were analyzed for subjective image quality; myocardial and fibrotic mass, and total fibrotic tissue percentage were quantified. There was no significant difference in subjective image quality between 3D and 2D acquisitions (P=0.1 and P=0.3) for either disease. In patients with Fabry disease there were no significant differences between 3D and 2D acquisitions for myocardial mass (P=0.55), fibrous tissue mass (P=0.89), and total fibrous percentage (P=0.67), with good agreement between acquisitions according to Bland-Altman analyses. In patients with HCM there were also no significant differences between acquisitions for myocardial mass (P=0.48), fibrous tissue mass (P=0.56), and total fibrous percentage (P=0.67), with good agreement according to Bland-Altman analyses. Acquisition time was significantly shorter for 3D (25±5s) as compared to the 2D sequence (349±62s, P<0.001). In patients with Fabry disease and HCM, 3D LGE imaging provides equivalent diagnostic information in regard to quantification of myocardial fibrosis as compared with a standard 2D sequence, but at superior acquisition speed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Enhanced Replication of Virulent Newcastle Disease Virus in Chicken Macrophages Is due to Polarized Activation of Cells by Inhibition of TLR7.

    Science.gov (United States)

    Zhang, Pingze; Ding, Zhuang; Liu, Xinxin; Chen, Yanyu; Li, Junjiao; Tao, Zhi; Fei, Yidong; Xue, Cong; Qian, Jing; Wang, Xueli; Li, Qingmei; Stoeger, Tobias; Chen, Jianjun; Bi, Yuhai; Yin, Renfu

    2018-01-01

    Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment. Although macrophages are considered to be one of the main target cells for NDV infection in vivo , very little is known about the ability of NDV to infect chicken macrophages, and virulence mechanisms of NDV as well as the polarized activation patterns of macrophages and correlation with viral infection and replication. In the present study, a cell culture model (chicken bone marrow macrophage cell line HD11) and three different virulence and genotypes of NDV (including class II virulent NA-1, class II lentogenic LaSota, and class I lentogenic F55) were used to solve the above underlying questions. Our data indicated that all three NDV strains had similar replication rates during the early stages of infection. Virulent NDV titers were shown to increase compared to the other lentogenic strains, and this growth was associated with a strong upregulation of both pro-inflammatory M1-like markers/cytokines and anti-inflammatory M2-like markers/cytokines in chicken macrophages. Virulent NDV was found to block toll-like receptor (TLR) 7 expression, inducing higher expression of type I interferons in chicken macrophages at the late stage of viral infection. Only virulent NDV replication can be inhibited by pretreatment with TLR7 ligand. Overall, this study demonstrated that virulent NDV activates a M1-/M2-like mixed polarized activation of chicken macrophages by inhibition of TLR7, resulting in enhanced replication compared to lentogenic viruses.

  12. Enhanced vector borne disease surveillance of California Culex mosquito populations reveals spatial and species-specific barriers of infection.

    Energy Technology Data Exchange (ETDEWEB)

    VanderNoot, Victoria A.; Curtis, Deanna Joy; Koh, Chung-Yan; Brodsky, Benjamin H; Lane, Todd

    2014-08-01

    Monitor i ng in f ectio n s in v ect o rs su c h as m osquit o es, s a nd fl i es, tsetse fl i es, a nd ticks to i denti f y hu m a n path o gens m a y s e r v e as a n ear l y w arn i ng det e ction system t o dir e ct loc a l g o v er n ment dise a se pr e v en t i v e m easu r e s . One major hurdle i n de t ection is the abi l i t y to scre e n l arge n u mbers of v e c t ors for h uman patho g ens w i thout t h e u s e of ge n o t y pe - s p ecific m o lecu l ar tec h nique s . N e x t genera t ion s equ e nc i ng (NG S ) pr o v i des a n unbi a sed p latfo r m capab l e of identi f y i ng k n o w n a n d unk n o w n p ath o ge n s circula t ing w i thin a v e ctor p opul a tion, but utili z ing t h is te c h nolo g y i s tim e - con s u ming a n d cos t l y for v ecto r -b o rne disease su r v e illan c e pr o gra m s. T o addr e s s this w e d e v e lop e d cos t -eff e ct i v e Ilumina(r) R NA- S eq l i bra r y p r epara t ion m e thodol o gies i n con j u n ction w i t h an automa t ed c ompu t at i onal a n a l y sis pipel i n e to ch a racter i ze t h e microbial popula t ions c ircula t i n g in Cu l e x m o squit o e s (Cul e x qui n quef a s c iatu s , C ul e x quinq u efasc i atus / pip i ens co m pl e x h y bri d s, and C u l e x ta r salis ) t hroug h out Californ i a. W e assembled 2 0 n o vel a n d w e l l -do c ume n ted a r b o v i ruses repres e nting mem b e rs of B u n y a v ir i da e , F l a v i virid a e, If a virida e , Meson i v i rida e , Nid o v iri d ae, O rtho m y x o virid a e, Pa r v o v iri d ae, Re o virid a e, R h a b d o v i rid a e, T y m o v iri d ae, a s w ell as s e v e r al u n assi g n e d v irus e s . In addit i o n, w e m app e d mRNA s pecies to d i vergent s peci e s of t r y panos o ma a nd pl a s modium eu k a r yotic parasit e s and cha r a c terized t he p r oka r yot i c microb i al c o mposit i on to i d enti f y bacteri a l tran s c r ipts der i v ed from wolba c hia, clo s tridi u m, m y c oplas m a, fusoba c

  13. Value of whole body MRI and dynamic contrast enhanced MRI in the diagnosis, follow-up and evaluation of disease activity and extent in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Dutoit, Julie C., E-mail: Julie.Dutoit@UGent.be; Vanderkerken, Matthias A., E-mail: Matthias.Vanderkerken@UGent.be; Verstraete, Koenraad L., E-mail: Koenraad.Verstraete@UGent.be

    2013-09-15

    Purpose: To evaluate the significance of dynamic contrast enhanced MRI (DCE-MRI) and whole body MRI (WB-MRI) in the diagnosis, prognosis and assessment of therapy for patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Materials and methods: The retrospective study includes 219 patients providing 463 WB-MRI and DCE-MRI investigations for the subgroups MGUS (n = 70), MM active disease (n = 126; this includes 70 patients with new diagnosis of MM, according to the International Staging System (ISS): 41.4% ISS stage I, 20.0% ISS stage II, 7.1% ISS stage III, 31.4% insufficient for staging; and 56 patients with ‘(re-)active disease’: 16.07% relapse, 32.14% progressive disease and 51.79% stable disease) and MM remission (n = 23; 60.87% complete remission, 17.39% very good partial remission and 21.74% partial remission). Investigations of patients with hereditary multiple exostoses (n = 5), neurofibromatosis (n = 7) and healthy persons (n = 9) were added as control subjects (n = 21). WB-MRI evaluation was done by evaluating thirteen skeletal regions, providing a ‘skeletal score’. DCE-MRI images of the spine, were analyzed with regions-of-interest and time-intensity-curves (TIC). Results: All TIC parameters can significantly differentiate between the predefined subgroups (p < 0.001). One hundred days after autologous stem cell transplantation a 75% decrease of the slope wash-in value (p < 0.001) can be seen. A cubic regression trend between ‘skeletal score’ and slope wash-in (adj.R{sup 2} = 0.412) could demonstrate a significant increase bone marrow perfusion if MM affects more than 10 skeletal regions (p < 0.001), associated with a poorer prognosis (p < 0.001). Conclusion: DCE-MRI evaluation of the spine is useful for diagnosis of MM, follow-up after stem cell transplantation and evaluation of disease activity. A combined evaluation with WB-MRI and DCE-MRI provides additional micro-vascular information on the

  14. Usefulness of T1 mapping on Gd-EOB-DTPA-enhanced MR imaging in assessment of non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Ding, Ying; Rao, Sheng-Xiang; Meng, Tao; Chen, Caizhong; Li, Renchen; Zeng, Meng-Su

    2014-01-01

    This study evaluates the value of Gd-EOB-DTPA-enhanced MRI for diagnosis and staging of non-alcoholic fatty liver disease (NAFLD) in an animal model by T 1 relaxation time measurement. Thirty-four rabbits were divided into the control group (n = 10) and NAFLD group, which was split into four groups (n = 6) with a high-fat diet for an interval of 3 weeks. A dual flip angle was performed before and at the hepatobiliary phase (HBP). T 1 relaxation times of the liver parenchyma and the decrease rate (∇%) were calculated. Histological findings according to semi-quantitative scoring of steatosis, activity and fibrosis were the standard of reference. HBP and ∇% T 1 relaxation time measurement showed significant differences between normal and NAFLD groups, between non-alcoholic steatohepatitis (NASH) and NAFLD without NASH (p = 0.000-0.049), between fibrosis groups (p = 0.000-0.019), but no difference between F1 and F2 (p = 0.834). The areas under the receiver operating characteristic curves (AUCs) of T 1 relaxation time for HBP and ∇% were 0.86-0.93 for the selection of NASH and activity score ≥2, and 0.86-0.95 for the selection of F ≥ 1, 2, 3. No significant difference was found for diagnostic performance between HBP and ∇% T 1 relaxation time. HBP T 1 relaxation time measurement of Gd-EOB-DTPA-enhanced MRI was useful to evaluate NAFLD according to the SAF score. HBP T 1 relaxation time measurement was as accurate as ∇% T 1 relaxation time. (orig.)

  15. Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical trials using a multi-biomarker disease activity score as an inclusion criterion.

    Science.gov (United States)

    van Vollenhoven, Ronald F; Bolce, Rebecca; Hambardzumyan, Karen; Saevarsdottir, Saedis; Forslind, Kristina; Petersson, Ingemar F; Sasso, Eric H; Hwang, C C; Segurado, Oscar G; Geborek, Pierre

    2015-11-01

    Rheumatoid arthritis (RA) clinical trials often exclude patients who have low C-reactive protein (CRP) levels, which slows enrollment into the trial. The purpose of this study was to determine whether high Multi-Biomarker Disease Activity (MBDA) scores (>44) in RA patients with low CRP levels (≤10 mg/liter) could be used as a complement to CRP levels >10 mg/liter to enhance patient recruitment without affecting clinical trial outcomes. We evaluated patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include any selection criteria for CRP levels. Clinical outcomes were assessed after 3 months of methotrexate (MTX) monotherapy in MTX-naive RA patients (n = 220) and after 3-10 months of add-on therapy in patients who were incomplete responders to MTX alone (MTX-IR) (n = 127). Radiographic outcomes were assessed at 1 year in all patients. Within each cohort, the outcomes were compared between patients with a CRP level of ≤10 mg/liter and an MBDA score of >44 at the start of the respective treatment interval versus those with a CRP level of >10 mg/liter. Patients with both a CRP level of ≤10 mg/liter and an MBDA score of >44 at baseline had clinical and radiographic outcomes that were comparable to those in patients with a CRP level of >10 mg/liter at baseline. This broadened definition of the inclusion criteria identified an additional 24% of patients in the MTX-naive cohort and 47% in the MTX-IR cohort. Patient recruitment into RA clinical trials may be substantially enhanced, without any decrease in clinical and radiographic outcomes, by using as an inclusion criterion "a CRP level of >10 mg/liter and/or an MBDA score of >44." © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  16. Usefulness of T1 mapping on Gd-EOB-DTPA-enhanced MR imaging in assessment of non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ying; Rao, Sheng-Xiang; Meng, Tao; Chen, Caizhong; Li, Renchen; Zeng, Meng-Su [Zhongshan/Hospital of Fudan University, Department of Radiology, Shanghai (China)

    2014-04-15

    This study evaluates the value of Gd-EOB-DTPA-enhanced MRI for diagnosis and staging of non-alcoholic fatty liver disease (NAFLD) in an animal model by T{sub 1} relaxation time measurement. Thirty-four rabbits were divided into the control group (n = 10) and NAFLD group, which was split into four groups (n = 6) with a high-fat diet for an interval of 3 weeks. A dual flip angle was performed before and at the hepatobiliary phase (HBP). T{sub 1} relaxation times of the liver parenchyma and the decrease rate (∇%) were calculated. Histological findings according to semi-quantitative scoring of steatosis, activity and fibrosis were the standard of reference. HBP and ∇% T{sub 1} relaxation time measurement showed significant differences between normal and NAFLD groups, between non-alcoholic steatohepatitis (NASH) and NAFLD without NASH (p = 0.000-0.049), between fibrosis groups (p = 0.000-0.019), but no difference between F1 and F2 (p = 0.834). The areas under the receiver operating characteristic curves (AUCs) of T{sub 1} relaxation time for HBP and ∇% were 0.86-0.93 for the selection of NASH and activity score ≥2, and 0.86-0.95 for the selection of F ≥ 1, 2, 3. No significant difference was found for diagnostic performance between HBP and ∇% T{sub 1} relaxation time. HBP T{sub 1} relaxation time measurement of Gd-EOB-DTPA-enhanced MRI was useful to evaluate NAFLD according to the SAF score. HBP T{sub 1} relaxation time measurement was as accurate as ∇% T{sub 1} relaxation time. (orig.)

  17. The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

    Science.gov (United States)

    Lee, Young Mok; Pan, Chi-Jiunn; Koeberl, Dwight D; Mansfield, Brian C; Chou, Janice Y

    2013-11-01

    Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia. © 2013.

  18. A novel GLP-1/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson's disease.

    Science.gov (United States)

    Yuan, Ziyue; Li, Dongfang; Feng, Peng; Xue, Guofang; Ji, Chenhui; Li, Guanglai; Hölscher, Christian

    2017-10-05

    Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD. Recently, dual GLP-1/GIP receptor agonists have been developed. We therefore tested the novel dual agonist DA3-CH in comparison with the best GLP-1 analogue currently on the market, liraglutide (both drugs 25nmol/kg ip once-daily for 7 days) in the MPTP mouse model of PD (25mg/kg ip once-daily for 7 days). In the Rotarod and grip strength assessment, DA3-CH was superior to liraglutide in reversing the MPTP-induced motor impairment. Dopamine synthesis as indicated by levels of tyrosine hydroxylase was much reduced by MPTP in the substantia nigra and striatum, and DA3-CH reversed this while liragutide only partially reversed this. The chronic inflammation response as shown in increased levels of activated microglia and astrocytes was reduced by both drugs. Importantly, expression levels of the neuroprotective growth factor Glial Derived Neurotrophic Factor (GDNF) was much enhanced by both DA3-CH and liragutide. The results demonstrate that the combination of GLP-1 and GIP receptor activation is superior to single GLP-1 receptor activation alone. Therefore, new dual agonists may be a promising treatment for PD. The GLP-1 receptor agonist exendin-4 has already shown disease modifying effects in clinical trials in PD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The effects of dopamine on regional cerebral blood flow in patients with Parkinson's disease before and after L-dopa. Measurement by Xe-enhanced CT

    International Nuclear Information System (INIS)

    Aiba, Ikuko; Indo, Toshikatsu; Takahashi, Akira.

    1994-01-01

    Regional cerebral blood flow (rCBF) was measured using the stable xenon enhanced CT method in previously untreated 13 patients with Parkinson's disease to evaluate CBF abnormality related to dysfunction of the nigrostriatal dopaminergic neurons. The patients comprised 5 men and 8 women with Hoehn-Yahr stage II-III. Age at onset ranged from 51 to 73 years (mean±SD, 61.8±8.9) and the duration of illness ranged from 1 to 96 months (15.1±24.1 months). In this series, there was no clinical evidence of hypertension, diabetes mellitus and cognitive impairment. rCBF was measured during 4-5-minutes inhalation, of 33% stable xenon gas-67% oxygen. The first measurement of rCBF was performed in all of the patients before L-dopa treatment. After initiation of L-dopa treatment (333.3±47.1 mg/day), the second measurement was carried out in 6 patients (1 man and 5 women) who had shown symptomatic improvement. The interval between both measurements was 57.7±16.9 days. The following results were obtained. 1) No significant CBF asymmetry was noted in any of the striatum, pallidum, thalamus, cerebrum, cerebellum and frontal lobe in untreated patients with Parkinson's disease. 2) After L-dopa treatment, rCBF was significantly increased only in the striatum as compared with the pretreatment level (51.9±9.3→63.1±9.9 ml/100g/min, p<0.01). 3) This increase was significantly greater on the more severely affected side (contralateral to the predominantly symptomatic limb) (p<0.05). These results suggest that the increase of rCBF in the striatum is closely related to functional improvement of the nigrostriatal dopaminergic neurons. (author)

  20. The Kidney Awareness Registry and Education (KARE) study: protocol of a randomized controlled trial to enhance provider and patient engagement with chronic kidney disease.

    Science.gov (United States)

    Tuot, Delphine S; Velasquez, Alexandra; McCulloch, Charles E; Banerjee, Tanushree; Zhu, Yunnuo; Hsu, Chi-yuan; Handley, Margaret; Schillinger, Dean; Powe, Neil R

    2015-10-22

    Chronic kidney disease (CKD) is common and is associated with excess mortality and morbidity. Better management could slow progression of disease, prevent metabolic complications, and reduce cardiovascular outcomes. Low patient awareness of CKD and ineffective patient-provider communication can impede such efforts. We developed provider and patient-directed interventions that harness health information technology to enhance provider recognition of CKD and delivery of guideline concordant care and augment patient understanding and engagement in CKD care. We report the design and protocol of the Kidney Awareness Registry and Education (KARE) Study, a 2x2 factorial randomized controlled trial that examines the impact of a multi-level intervention on health outcomes among low-income English, Spanish and Cantonese-speaking patients with CKD in a safety net system. The intervention includes: (1) implementation of a primary care electronic CKD registry that notifies practice teams of patients' CKD status and employs a patient profile and quarterly feedback to encourage provision of guideline-concordant care at point-of-care and via outreach; and (2) a language-concordant, culturally-sensitive self-management support program that consists of automated telephone modules, provision of low-literacy written patient-educational materials and telephone health coaching. The primary outcomes of the trial are changes in systolic blood pressure (BP) and the proportion of patients with BP control (≤ 140/90 mmHg) after one year. Secondary outcomes include patient understanding of CKD, participation in healthy behaviors, and practice team delivery of guideline-concordant CKD care. Results from the KARE study will provide data on the feasibility, effectiveness, and acceptability of technology-based interventions that support primary care efforts at improving health outcomes among vulnerable patients with CKD. ClinicalTrials.gov, number: NCT01530958.

  1. Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells.

    Science.gov (United States)

    Ma, Hak-Ling; Napierata, Lee; Stedman, Nancy; Benoit, Stephen; Collins, Mary; Nickerson-Nutter, Cheryl; Young, Deborah A

    2010-02-01

    Patients with psoriasis and psoriatic arthritis respond well to tumor necrosis factor alpha (TNFalpha) blockers in general; however, there is now mounting evidence that a small cohort of patients with rheumatoid arthritis who receive TNFalpha blockers develop psoriasis. This study was undertaken to explore the mechanisms underlying TNFalpha blockade-induced exacerbation of skin inflammation in murine psoriasis-like skin disease. Skin inflammation was induced in BALB/c scid/scid mice after they received CD4+CD45RB(high)CD25- (naive CD4) T cells from donor mice. These mice were treated with either anti-interleukin-12 (anti-IL-12)/23p40 antibody or murine TNFRII-Fc fusion protein and were examined for signs of disease, including histologic features, various cytokine levels in the serum, and cytokine or FoxP3 transcripts in the affected skin and draining lymph node (LN) cells. In a separate study, naive CD4+ T cells were differentiated into Th1 or Th17 lineages with anti-CD3/28 magnetic beads and appropriate cytokines in the presence or absence of TNFalpha. Cytokine gene expression from these differentiated cells was also determined. Neutralization of TNFalpha exacerbated skin inflammation and markedly enhanced the expression of the proinflammatory cytokines IL-1beta, IL-6, IL-17, IL-21, and IL-22 but suppressed FoxP3 expression in the skin and reduced the number of FoxP3-positive Treg cells in the draining LNs. TNFalpha also demonstrated a divergent role during priming and reactivation of naive T cells. These results reveal a novel immunoregulatory role of TNFalpha on Th17 and Treg cells in some individuals, which may account for the exacerbation of skin inflammation in some patients who receive anti-TNF treatments.

  2. The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART).

    Science.gov (United States)

    Jernberg, Tomas; Attebring, Mona F; Hambraeus, Kristina; Ivert, Torbjorn; James, Stefan; Jeppsson, Anders; Lagerqvist, Bo; Lindahl, Bertil; Stenestrand, Ulf; Wallentin, Lars

    2010-10-01

    The aims of the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) are to support the improvement of care and evidence-based development of therapy of coronary artery disease (CAD). To provide users with online interactive reports monitoring the processes of care and outcomes and allowing direct comparisons over time and with other hospitals. National, regional and county-based reports are publicly presented on a yearly basis. Every hospital (n=74) in Sweden providing the relevant services participates. Launched in 2009 after merging four national registries on CAD. Consecutive acute coronary syndrome (ACS) patients, and patients undergoing coronary angiography/angioplasty or heart surgery. Includes approximately 80, 000 new cases each year. On admission in ACS patients, at coronary angiography in patients with stable CAD. 106 variables for patients with ACS, another 75 variables regarding secondary prevention after 12-14 months, 150 variables for patients undergoing coronary angiography/angioplasty, 100 variables for patients undergoing heart surgery. Web-based registry with all data registered online directly by the caregiver. A monitor visits approximately 20 hospitals each year. In 2007, there was a 96% agreement. Merged with the National Cause of Death Register, including information about vital status of all Swedish citizens, the National Patient Registry, containing diagnoses at discharge for all hospital stays in Sweden and the National Registry of Drug prescriptions recording all drug prescriptions in Sweden. Available for research by application to the SWEDEHEART steering group.

  3. Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Path to a Dengue Vaccine: Learning from Human Natural Dengue Infection Studies and Vaccine Trials.

    Science.gov (United States)

    de Silva, Aravinda M; Harris, Eva

    2018-06-01

    Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in human clinical trials. Initial results are mixed, with variable efficacy depending on DENV serotype and previous DENV exposure. Here, we highlight recent discoveries about the human antibody response to DENV and propose guidelines for advancing development of safe and effective dengue vaccines. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  4. Enhancing evidence-based diabetes and chronic disease control among local health departments: a multi-phase dissemination study with a stepped-wedge cluster randomized trial component.

    Science.gov (United States)

    Parks, Renee G; Tabak, Rachel G; Allen, Peg; Baker, Elizabeth A; Stamatakis, Katherine A; Poehler, Allison R; Yan, Yan; Chin, Marshall H; Harris, Jenine K; Dobbins, Maureen; Brownson, Ross C

    2017-10-18

    The rates of diabetes and prediabetes in the USA are growing, significantly impacting the quality and length of life of those diagnosed and financially burdening society. Premature death and disability can be prevented through implementation of evidence-based programs and policies (EBPPs). Local health departments (LHDs) are uniquely positioned to implement diabetes control EBPPs because of their knowledge of, and focus on, community-level needs, contexts, and resources. There is a significant gap, however, between known diabetes control EBPPs and actual diabetes control activities conducted by LHDs. The purpose of this study is to determine how best to support the use of evidence-based public health for diabetes (and related chronic diseases) control among local-level public health practitioners. This paper describes the methods for a two-phase study with a stepped-wedge cluster randomized trial that will evaluate dissemination strategies to increase the uptake of public health knowledge and EBPPs for diabetes control among LHDs. Phase 1 includes development of measures to assess practitioner views on and organizational supports for evidence-based public health, data collection using a national online survey of LHD chronic disease practitioners, and a needs assessment of factors influencing the uptake of diabetes control EBPPs among LHDs within one state in the USA. Phase 2 involves conducting a stepped-wedge cluster randomized trial to assess effectiveness of dissemination strategies with local-level practitioners at LHDs to enhance capacity and organizational support for evidence-based diabetes prevention and control. Twelve LHDs will be selected and randomly assigned to one of the three groups that cross over from usual practice to receive the intervention (dissemination) strategies at 8-month intervals; the intervention duration for groups ranges from 8 to 24 months. Intervention (dissemination) strategies may include multi-day in-person workshops, electronic

  5. A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease.

    Science.gov (United States)

    Wiegand, Marian Alexander; Gori-Savellini, Gianni; Gandolfo, Claudia; Papa, Guido; Kaufmann, Christine; Felder, Eva; Ginori, Alessandro; Disanto, Maria Giulia; Spina, Donatella; Cusi, Maria Grazia

    2017-05-15

    Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity

  6. Neuropeptide Treatment with Cerebrolysin Enhances the Survival of Grafted Neural Stem Cell in an α-Synuclein Transgenic Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Edward Rockenstein

    2015-01-01

    Full Text Available Neuronal stem cell (NSC grafts have been investigated as a potential neuro-restorative therapy in Parkinson's disease (PD but their use is compromised by the death of grafted cells. We investigated the use of Cerebrolysin (CBL, a neurotrophic peptide mixture, as an adjunct to NSC therapy in the α-synuclein (α-syn transgenic (tg model of PD. In vehicle-treated α-syn tg mice, there was decreased survival of NSCs. In contrast, CBL treatment enhanced the survival of NSCs in α-syn tg groups and ameliorated behavioral deficits. The grafted NSCs showed lower levels of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in the CBL-treated mice when compared with vehicle-treated α-syn tg mice. No evidence of tumor growth was detected. Levels of α-syn were similar in the vehicle in CBL-treated tg mice. In conclusion, CBL treatment might be a potential adjuvant for therapeutic NSC grafting in PD.

  7. Enhanced cued recall has a high utility as a screening test in the diagnosis of Alzheimer's disease and mild cognitive impairment in Turkish people.

    Science.gov (United States)

    Saka, Esen; Mihci, Ebru; Topcuoglu, M Akif; Balkan, Sevin

    2006-10-01

    Enhanced cued recall (ECR) is highly sensitive and specific in discrimination of demented from non-demented elderly persons. The nature of the test promises that it can be applicable to subjects in different cultures and education level. We studied the utility of the test in a Turkish population. Eighty consecutive cases with dementia or mild cognitive impairment (MCI) and 33 elderly controls were studied. The utility of ECR was high in discriminating dementia from controls (area under curve (AUC)) of the ROC curve: 0.907 (95% confidence interval (CI): 0.830-0.953 for total recall), Alzheimer's disease from controls (AUC: 0.990 (95%CI: 0.934-0.998 for total recall)) and moderate (AUC: 0.625 (95%CI: 0.545-0.812 for third free recall)) in discriminating MCI from controls. Education did not affect the utility of the test. We conclude that ECR is a valuable test in assessment of elderly Turkish patients with a complaint of memory impairment.

  8. Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study)

    Energy Technology Data Exchange (ETDEWEB)

    Deray, Gilbert [Pitie Salpetriere Hospital, Department of Nephrology, Paris cedex 13 (France); Rouviere, Olivier [Hopital E. Herriot, Universite de Lyon, Hospices Civils de Lyon, Department of Urinary and Vascular Imaging, Lyon (France); Universite Lyon 1, faculte de medecine Lyon Est, Lyon (France); Bacigalupo, Lorenzo [E.O. Ospedali Galliera, Radiology Department, Genova (Italy); Maes, Bart [Heilig Hartziekenhuis Roeselare, Department of Nephrology, Roeselare (Belgium); Hannedouche, Thierry [University Hospitals, Department of Nephrology, Strasbourg (France); Vrtovsnik, Francois [Bichat Hospital, Department of Nephrology, Paris (France); Rigothier, Claire [Pellegrin Hospital, Department of Nephrology Transplantation Dialysis, Bordeaux (France); Billiouw, Jean-Marie [Onze Lieve Vrouw Ziekenhuis, Department of Nephrology, Aalst (Belgium); Campioni, Paolo [Azienda Ospedaliero-Universitaria Sant' Anna, Ferrara (Italy); Ferreiros, Joaquin [Hospital Clinico de San Carlos, Servicio de Radiodiagnostico, Madrid (Spain); Devos, Daniel [Gent University Hospital, Department of Radiology, Gent (Belgium); Alison, Daniel [Trousseau Hospital, Department of Radiology, Tours (France); Glowacki, Francois [University Hospitals, Department of Nephrology, Lille (France); Boffa, Jean-Jacques [Tenon Hospital, Department of Nephrology and Dialysis, Paris (France); Marti-Bonmati, Luis [University of Valencia, Department of Radiology, Valencia (Spain)

    2013-05-15

    To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 {+-} 24 h after the MRI procedure, by at least 25 % or 44.2 {mu}mol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at -15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 {+-} 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up. Among the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [{Delta} = -1.4 %, 95%CI = (-7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted. Meglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD. (orig.)

  9. Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study)

    International Nuclear Information System (INIS)

    Deray, Gilbert; Rouviere, Olivier; Bacigalupo, Lorenzo; Maes, Bart; Hannedouche, Thierry; Vrtovsnik, Francois; Rigothier, Claire; Billiouw, Jean-Marie; Campioni, Paolo; Ferreiros, Joaquin; Devos, Daniel; Alison, Daniel; Glowacki, Francois; Boffa, Jean-Jacques; Marti-Bonmati, Luis

    2013-01-01

    To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 μmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at -15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up. Among the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [Δ = -1.4 %, 95%CI = (-7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted. Meglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD. (orig.)

  10. Thrombogenicity and central pulse pressure to enhance prediction of ischemic event occurrence in patients with established coronary artery disease: The MAGMA-ischemia score.

    Science.gov (United States)

    Bliden, Kevin P; Chaudhary, Rahul; Navarese, Eliano P; Sharma, Tushar; Kaza, Himabindu; Tantry, Udaya S; Gurbel, Paul A

    2018-01-01

    Conventional cardiovascular risk estimators based on clinical demographics have limited prediction of coronary events. Markers for thrombogenicity and vascular function have not been explored in risk estimation of high-risk patients with coronary artery disease. We aimed to develop a clinical and biomarker score to predict 3-year adverse cardiovascular events. Four hundred eleven patients, with ejection fraction ≥40% undergoing coronary angiography, and found to have a luminal diameter stenosis ≥50%, were included in the analysis. Thrombelastography indices and central pulse pressure (CPP) were determined at the time of catheterization. We identified predictors of death, myocardial infarction (MI) or stroke and developed a numerical ischemia risk score. The primary endpoint of cardiovascular death, MI or stroke occurred in 22 patients (5.4%). The factors associated with events were age, prior PCI or CABG, diabetes, CPP, and thrombin-induced platelet-fibrin clot strength, and were included in the MAGMA-ischemia score. The MAGMA-ischemia score showed a c-statistic of 0.85 (95% Confidence Interval [CI] 0.80-0.87; pMAGMA-ischemia score greater than 5 had highest risk to develop clinical events, hazard ratio for the primary endpoint: 13.9 (95% CI 5.8-33.1, pMAGMA-ischemia score yielded a higher discrimination. Inclusion of CPP and assessment of thrombogenicity in a novel score for patients with documented CAD enhanced the prediction of events. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Laboratory validation of two real-time RT-PCR methods with 5'-tailed primers for an enhanced detection of foot-and-mouth disease virus.

    Science.gov (United States)

    Vandenbussche, Frank; Lefebvre, David J; De Leeuw, Ilse; Van Borm, Steven; De Clercq, Kris

    2017-08-01

    The 3D and 5UTR real-time RT-PCR assays (RT-qPCR) from Callahan et al. (2002) and Reid et al. (2002) are commonly used reference methods for the detection of foot-and-mouth disease virus (FMDV). For an optimal detection of FMDV in clinical samples, it is advised to use both assays simultaneously (King et al., 2006). Recently, Vandenbussche et al. (2016) showed that the addition of 5'-tails to the FMDV-specific primers enhances the detection of FMDV in both the 3D and the 5UTR RT-qPCR assay. To validate the 3D and 5UTR RT-qPCR assays with 5'-tailed primers for diagnostic purposes, both assays were run in parallel in a triplex one-step RT-qPCR protocol with beta-actin as an internal control and synthetic RNA as an external control. We obtained low limits of detection and high linearity's, high repeatability and reproducibility, near 100% analytical specificity and >99% diagnostic accuracy for both assays. It was concluded that the 3D and 5UTR RT-qPCR assays with 5'-tailed primers are particularly suited for the detection of FMDV as well as to exclude the presence of FMDV. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Diet enriched with mushroom Phellinus linteus extract enhances the growth, innate immune response, and disease resistance of kelp grouper, Epinephelus bruneus against vibriosis.

    Science.gov (United States)

    Harikrishnan, Ramasamy; Balasundaram, Chellam; Heo, Moon-Soo

    2011-01-01

    The effect of diet supplemented with Phellinus linteus fed for 30 days was investigated in grouper Epinephelus bruneus challenged with Vibrio anguillarum, Vibrio harveyi, Vibrio alginolyticus, and Vibrio carchariae; infected and treated fish had a significantly higher percent weight gain and feed efficiency. In groups fed with enriched diet and challenged with V. anguillarum and V. harveyi the mortality rate declined with a consequent rise in survival rate than with other pathogens. On the other hand, in groups fed with P. linteus enriched diet and challenged with V. anguillarum, V. harveyi, and V. alginolyticus the cellular and humoral immune responses, such as the alternative complement activity (ACH(50)), serum lysozyme activity, phagocytic activity (PA), phagocytic index (PI) significantly higher than in the control group. The respiratory bursts (RB), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were found significantly enhanced when the groups fed with enriched diet against V. anguillarum and V. harveyi. The results reveal that kelp grouper fed for 30 days with P. linteus enriched diet had higher cellular and humoral immune response and disease protection from vibriosis than the group fed on basal diet with the protection linked to stimulation of immune system. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Effects of a Whatsapp-delivered physical activity intervention to enhance health-related physical fitness components and cardiovascular disease risk factors in older adults.

    Science.gov (United States)

    Muntaner-Mas, Adrià; Vidal-Conti, Josep; Borràs, Pere A; Ortega, Francisco B; Palou, Pere

    2017-01-01

    This pilot study evaluated the feasibility and preliminary effectiveness of a 10-week WhatsApp-based intervention aimed at enhancing health-related physical fitness components and cardiovascular disease (CVD) risk factors compared with a face-to-face condition. Participants (N.=32) were assigned to one of three groups: training group (N.=16), mobile group (N.=7) and control group (N.=9). Training group and mobile group performed the same training program, based on strength training with elastics bands and aerobic exercise, during 10 weeks; only the delivery mode differed. The mobile group increased handgrip strength, aerobic capacity and decreased systolic blood pressure and heart rate after exercise though there were no significant differences respect to control group. The training group decreased significantly systolic blood pressure (P=0.038), diastolic blood pressure (P=0.005), mean arterial pressure (P=0.006) and heart rate after exercise (P=0.002), respect to control group. Comparison between training and mobile group showed that WhatsApp-based physical activity intervention was less effective than face-to-face condition. The results indicate that the use of an online social network produced slight changes in some health-related physical fitness components and CVD risk factors.

  14. Characterization of foot- and mouth disease virus antigen by surface-enhanced laser desorption ionization-time of flight-mass spectrometry in aqueous and oil-emulsion formulations

    NARCIS (Netherlands)

    Harmsen, M.M.; Jansen, J.; Westra, D.F.; Coco-Martin, J.M.

    2010-01-01

    We have used a novel method, surface-enhanced laser desorption ionization-time of flight-mass spectrometry (SELDI-TOF-MS), to characterize foot-and-mouth disease virus (FMDV) vaccine antigens. Using specific capture with FMDV binding recombinant antibody fragments and tryptic digestion of FMDV

  15. Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8+ TEM and TRM Cell Responses against Herpesvirus Infection and Disease.

    Science.gov (United States)

    Lopes, Patricia P; Todorov, George; Pham, Thanh T; Nesburn, Anthony B; Bahraoui, Elmostafa; BenMohamed, Lbachir

    2018-04-15

    There is an urgent need for chemical-free and biological-free safe adjuvants to enhance the immunogenicity of vaccines against widespread viral pathogens, such as herpes simplex virus 2 (HSV-2), that infect a large proportion of the world human population. In the present study, we investigated the safety, immunogenicity, and protective efficacy of a laser adjuvant-assisted peptide (LAP) vaccine in the B6 mouse model of genital herpes. This LAP vaccine and its laser-free peptide (LFP) vaccine analog contain the immunodominant HSV-2 glycoprotein B CD8 + T cell epitope (HSV-gB 498-505 ) covalently linked with the promiscuous glycoprotein D CD4 + T helper cell epitope (HSV-gD 49-89 ). Prior to intradermal delivery of the LAP vaccine, the lower-flank shaved skin of B6 or CD11c/eYFP transgenic mice received a topical skin treatment with 5% imiquimod cream and then was exposed for 60 s to a laser, using the FDA-approved nonablative diode. Compared to the LFP vaccine, the LAP vaccine (i) triggered mobilization of dendritic cells (DCs) in the skin, which formed small spots along the laser-treated areas, (ii) induced phenotypic and functional maturation of DCs, (iii) stimulated long-lasting HSV-specific effector memory CD8 + T cells (T EM cells) and tissue-resident CD8 + T cells (T RM cells) locally in the vaginal mucocutaneous tissues (VM), and (iv) induced protective immunity against genital herpes infection and disease. As an alternative to currently used conventional adjuvants, the chemical- and biological-free laser adjuvant offers a well-tolerated, simple-to-produce method to enhance mass vaccination for widespread viral infections. IMPORTANCE Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world population. There is an urgent need for chemical-free and biological-free safe adjuvants that would advance mass vaccination against the widespread herpes infections. The present study demonstrates that immunization with a laser

  16. The NS1 glycoprotein can generate dramatic antibody-enhanced dengue viral replication in normal out-bred mice resulting in lethal multi-organ disease.

    Directory of Open Access Journals (Sweden)

    Andrew K I Falconar

    Full Text Available Antibody-enhanced replication (AER of dengue type-2 virus (DENV-2 strains and production of antibody-enhanced disease (AED was tested in out-bred mice. Polyclonal antibodies (PAbs generated against the nonstructural-1 (NS1 glycoprotein candidate vaccine of the New Guinea-C (NG-C or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD₅₀ of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS, displayed by diffuse alveolar damage (DAD resulting from i dramatic interstitial alveolar septa-thickening with mononuclear cells, ii some hyperplasia of alveolar type-II pneumocytes, iii copious intra-alveolar protein secretion, iv some hyaline membrane-covered alveolar walls, and v DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human "severe dengue" cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines

  17. The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences.

    Science.gov (United States)

    Schäfer, Ingmar; Küver, Claudia; Gedrose, Benjamin; Hoffmann, Falk; Russ-Thiel, Barbara; Brose, Hans-Peter; van den Bussche, Hendrik; Kaduszkiewicz, Hanna

    2010-03-03

    In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year. Cohort study with a baseline interview and a follow-up after 10.4 +/- 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses. DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have > or = 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up. In the light of patient's experiences the DMP enhances the process quality of medical care for type 2

  18. Low perceived social support and post-myocardial infarction prognosis in the enhancing recovery in coronary heart disease clinical trial: the effects of treatment.

    Science.gov (United States)

    Burg, Matthew M; Barefoot, John; Berkman, Lisa; Catellier, Diane J; Czajkowski, Susan; Saab, Patrice; Huber, Marc; DeLillo, Vicki; Mitchell, Pamela; Skala, Judy; Taylor, C Barr

    2005-01-01

    In post hoc analyses, to examine in low perceived social support (LPSS) patients enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial (n = 1503), the pattern of social support following myocardial infarction (MI), the impact of psychosocial intervention on perceived support, the relationship of perceived support at the time of MI to subsequent death and recurrent MI, and the relationship of change in perceived support 6 months after MI to subsequent mortality. Partner status (partner, no partner) and score (12 = moderate support) on the ENRICHD Social Support Instrument (ESSI) were used post hoc to define four levels of risk. The resulting 4 LPSS risk groups were compared on baseline characteristics, changes in social support, and medical outcomes to a group of concurrently enrolled acute myocardial infarction patients without depression or LPSS (MI comparison group, n = 408). Effects of treatment assignment on LPSS and death/recurrent MI were also examined. All 4 LPSS risk groups demonstrated improvement in perceived support, regardless of treatment assignment, with a significant treatment effect only seen in the LPSS risk group with no partner and moderate support at baseline. During an average 29-month follow-up, the combined end point of death/nonfatal MI was 10% in the MI comparison group and 23% in the ENRICHD LPSS patients; LPSS conferred a greater risk in unadjusted and adjusted models (HR = 1.74-2.39). Change in ESSI score and/or improvement in perceived social support were not found to predict subsequent mortality. Baseline LPSS predicted death/recurrent MI in the ENRICHD cohort, independent of treatment assignment. Intervention effects indicated a partner surrogacy role for the interventionist and the need for a moderate level of support at baseline for the intervention to be effective.

  19. Combined administration of low molecular weight sodium alginate boosted immunomodulatory, disease resistance and growth enhancing effects of Lactobacillus plantarum in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Van Doan, Hien; Hoseinifar, Seyed Hossein; Tapingkae, Wanaporn; Tongsiri, Sudaporn; Khamtavee, Pimporn

    2016-11-01

    The present study investigates the effects of combined or singular administration of low molecular weight sodium alginate (LWMSA) and Lactobacillus plantarum on innate immune response, disease resistance and growth performance of Nile tilapia (Oreochromis niloticus). Three hundred and twenty fish were supplied and randomly stocked in sixteen glass tanks (150 L) assigned to four treatments as follows: 0 g kg -1 LMWSA (Control, Diet 1), 10 g kg -1 LMWSA (Diet 2), 10 8  CFU g -1 L. plantarum (Diet 3), and 10 g kg -1 LMWSA + 10 8  CFU g -1 L. plantarum (Diet 4). Following 30 and 60 days of the feeding trial, serum lysozyme, phagocytosis, respiratory burst and alternative complement activities as well as growth performance parameters (specific growth rate, feed conversion ratio) were measured. Serum lysozyme, phagocytosis, respiratory burst, and alternative complement activities of fish were significantly stimulated by both LMWSA and L. plantarum diets, however, the highest innate immune response were observed in fish fed synbiotic diet. At the end of the experiment, eight fish per replication were randomly selected for a challenge test against Streptococcus agalactiae. The survival rate of the fish fed supplemented diets was significantly greater than the control treatment and the highest post challenge survival rate was observed in synbiotic diet. Furthermore, SGR and FCR were significantly improved in fish fed supplemented diets after 60 days and the highest growth performance was observed in fish fed synbiotic diet. These results suggest combined LMWSA and L. plantarum can be considered as a promising immunostimulant and growth enhancer in Nile tilapia diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Susceptibility to viral infection is enhanced by stable expression of 3A or 3AB proteins from foot-and-mouth disease virus

    International Nuclear Information System (INIS)

    Rosas, Maria F.; Vieira, Yuri A.; Postigo, Raul; Martin-Acebes, Miguel A.; Armas-Portela, Rosario; Martinez-Salas, Encarnacion; Sobrino, Francisco

    2008-01-01

    The foot-and-mouth disease virus (FMDV) 3A protein is involved in virulence and host range. A distinguishing feature of FMDV 3B among picornaviruses is that three non-identical copies are encoded in the viral RNA and required for optimal replication in cell culture. Here, we have studied the involvement of the 3AB region on viral infection using constitutive and transient expression systems. BHK-21 stably transformed clones expressed low levels of FMDV 3A or 3A(B) proteins in the cell cytoplasm. Transformed cells stably expressing these proteins did not exhibit inner cellular rearrangements detectable by electron microscope analysis. Upon FMDV infection, clones expressing either 3A alone or 3A(B) proteins showed a significant increase in the percentage of infected cells, the number of plaque forming units and the virus yield. The 3A-enhancing effect was specific for FMDV as no increase in viral multiplication was observed in transformed clones infected with another picornavirus, encephalomyocarditis virus, or the negative-strand RNA virus vesicular stomatitis virus. A potential role of 3A protein in viral RNA translation was discarded by the lack of effect on FMDV IRES-dependent translation. Increased viral susceptibility was not caused by a released factor; neither the supernatant of transformed clones nor the addition of purified 3A protein to the infection medium was responsible for this effect. Unlike stable expression, high levels of 3A or 3A(B) protein transient expression led to unspecific inhibition of viral infection. Therefore, the effect observed on viral yield, which inversely correlated with the intracellular levels of 3A protein, suggests a transacting role operating on the FMDV multiplication cycle

  1. Genetic myostatin decrease in the golden retriever muscular dystrophy model does not significantly affect the ubiquitin proteasome system despite enhancing the severity of disease.

    Science.gov (United States)

    Cotten, Steven W; Kornegay, Joe N; Bogan, Daniel J; Wadosky, Kristine M; Patterson, Cam; Willis, Monte S

    2013-01-01

    Recent studies suggest that inhibiting the protein myostatin, a negative regulator of skeletal muscle mass, may improve outcomes in patients with Duchenne muscular dystrophy by enhancing muscle mass. When the dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog was bred with whippets having a heterozygous mutation for the myostatin gene, affected GRMD dogs with decreased myostatin (GRippets) demonstrated an accelerated physical decline compared to related affected GRMD dogs with full myostatin. To examine the role of the ubiquitin proteasome and calpain systems in this accelerated decline, we determined the expression of the muscle ubiquitin ligases MuRF1, Atrogin-1, RNF25, RNF11, and CHIP: the proteasome subunits PSMA6, PSMB4, and PSME1: and calpain 1/2 by real time PCR in the cranial sartorius and vastus lateralis muscles in control, affected GRMD, and GRippet dogs. While individual affected GRMD and GRippet dogs contributed to an increased variability seen in ubiquitin ligase expression, neither group was significantly different from the control group. The affected GRMD dogs demonstrated significant increases in caspase-like and trypsin-like activity in the cranial sartorius; however, all three proteasome activities in the GRippet muscles did not differ from controls. Increased variability in calpain 1 and calpain 2 expression and activity in the affected GRMD and GRippet groups were identified, but no statistical differences from the control group were seen. These studies suggest a role of myostatin in the disease progression of GRMD, which does not significantly involve key components of the ubiquitin proteasome and calpain systems involved in the protein quality control of sarcomere and other structural skeletal muscle proteins.

  2. Protocol for hospital based-surveillance of cerebral palsy (CP) in Hanoi using the Paediatric Active Enhanced Disease Surveillance mechanism (PAEDS-Vietnam): a study towards developing hospital-based disease surveillance in Vietnam.

    Science.gov (United States)

    Khandaker, Gulam; Van Bang, Nguyen; Dũng, Trịnh Quang; Giang, Nguyen Thi Huong; Chau, Cao Minh; Van Anh, Nguyen Thi; Van Thuong, Nguyen; Badawi, Nadia; Elliott, Elizabeth J

    2017-11-09

    The epidemiology, pathogenesis, management and outcomes of cerebral palsy (CP) in low-income and middle-income countries including Vietnam are unknown because of the lack of mechanisms for standardised collection of data. In this paper, we outline the protocol for developing a hospital-based surveillance system modelled on the Paediatric Active Enhanced Disease Surveillance (PAEDS) system in Australia. Using PAEDS-Vietnam we will define the aetiology, motor function and its severity, associated impairments, and nutritional and rehabilitation status of children with CP in Hanoi, Vietnam. These essential baseline data will inform future health service planning, health professional education and training, and family support. This is a hospital-based prospective surveillance of children with CP presenting to the rehabilitation, neurology and general paediatric services at the National Children's Hospital and St Paul Hospital in Hanoi. We will use active, prospective daily case-finding for all children with CP aged CP, known risk factors for CP, and nutrition, immunisation, education and rehabilitation status. This study was approved by the Hanoi Medical University Institutional Review Board (decision no 1722) and The University of Sydney Human Research Ethics Committee (approval no 2016/456). Establishment of PAEDS-Vietnam will enable hospital-based surveillance of CP for the first time in Vietnam. It will identify preventable causes of CP, patient needs and service gaps, and facilitate early diagnosis and intervention. Study findings will be disseminated through local and international conferences and peer-reviewed publications. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Quantitation of myocardial blood flow and myocardial flow reserve with {sup 99m}Tc-sestamibi dynamic SPECT/CT to enhance detection of coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Bailing [University of Missouri-Columbia, Nuclear Science and Engineering Institute, Columbia, MO (United States); Chen, Fu-Chung; Chen, Chien-Cheng [Show Chwan Memorial Hospital, Section of Cardiology, Department of Internal Medicine, Changhua (China); Wu, Tao-Cheng [Taipei Veterans General Hospital, Section of Cardiology, Department of Internal Medicine, Taipei (China); Huang, Wen-Sheng [Changhua Christian Hospital, Department of Medical Research and Department of Nuclear Medicine, Changhua (China); Hou, Po-Nien [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Lukong Town, Changhua Shien (China); Hung, Guang-Uei [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Lukong Town, Changhua Shien (China); Central Taiwan University of Science and Technology, Department of Medical Imaging and Radiological Science, Taichung (China); China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China)

    2014-12-15

    Conventional dual-head single photon emission computed tomography (SPECT)/CT systems capable of fast dynamic SPECT (DySPECT) imaging have a potential for flow quantitation. This study introduced a new method to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) with DySPECT scan and evaluated the diagnostic performance of detecting coronary artery disease (CAD) compared with perfusion using invasive coronary angiography (CAG) as the reference standard. This study included 21 patients with suspected or known CAD who had received DySPECT, ECG-gated SPECT (GSPECT), and CAG (13 with ≥50 % stenosis in any vessel; non-CAD group: 8 with patent arteries or <50 % stenosis). DySPECT and GSPECT scans were performed on a widely used dual-head SPECT/CT scanner. The DySPECT imaging protocol utilized 12-min multiple back-and-forth gantry rotations during injections of {sup 99m}Tc-sestamibi (MIBI) tracer at rest or dipyridamole-stress stages. DySPECT images were reconstructed with full physical corrections and converted to the physical unit of becquerels per milliliter. Stress MBF (SMBF), rest MBF (RMBF), and MFR were quantified by a one-tissue compartment flow model using time-activity curves derived from DySPECT images. Perfusion images were processed for GSPECT scan and interpreted to obtain summed stress score (SSS) and summed difference score (SDS). Receiver-operating characteristic (ROC) analyses were conducted to evaluate the diagnostic performance of flow and perfusion. Using the criteria of ≥50 % stenosis as positive CAD, areas under the ROC curve (AUCs) of flow assessment were overall significantly greater than those of perfusion. For patient-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.91 ± 0.07, 0.86 ± 0.09, 0.64 ± 0.12, and 0.59 ± 0.13. For vessel-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.81 ± 0.05, 0.76 ± 0.06, 0.62 ± 0.07, and 0.56 ± 0.08, respectively. The preliminary data suggest that MBF quantitation with a

  4. Potentiated clinoptilolite: artificially enhanced aluminosilicate reduces symptoms associated with endoscopically negative gastroesophageal reflux disease and nonsteroidal anti-inflammatory drug induced gastritis

    Directory of Open Access Journals (Sweden)

    Potgieter W

    2014-07-01

    Full Text Available Wilna Potgieter, Caroline Selma Samuels, Jacques Renè SnymanDepartment of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, Gauteng, South AfricaPurpose: The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D, is a synthetically enhanced aluminosilicate. The aim of this study was to evaluate the possible benefits of a potentiated clinoptilolite as a gastroprotective agent in reducing the severity of clinical symptoms and signs associated with 1 endoscopically negative gastroesophageal reflux disease (ENGORD and 2 nonsteroidal anti-inflammatory drug (NSAID medication.Methods and patients: Two randomized, double-blind, placebo-controlled, pilot studies, the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy, a total of 25 patients suffering from ENGORD were randomized to receive either placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent gastroscopic evaluation of their stomach linings prior to and on day 14 of the study. Gastric biopsies were obtained and evaluated via the upgraded Sydney system, whereas visible gastric events and status of the gastric mucosa were evaluated via a 0–3 rating scale. During both studies, patients recorded gastric symptoms in a daily symptom diary.Results: In the ENGORD study, patients who received the potentiated clinoptilolite reported a significant reduction (P≤0.05 in severity of symptoms including reduction in heartburn (44%, discomfort (54%, and pain (56%. Symptom-free days improved by 41% compared to the group who received placebo (not significant. This was over and above the benefits seen with the proton pump inhibitor. In the NSAID study, the reduction in gastric symptom severity was echoed in the group who received the potentiated

  5. Quantitation of myocardial blood flow and myocardial flow reserve with 99mTc-sestamibi dynamic SPECT/CT to enhance detection of coronary artery disease

    International Nuclear Information System (INIS)

    Hsu, Bailing; Chen, Fu-Chung; Chen, Chien-Cheng; Wu, Tao-Cheng; Huang, Wen-Sheng; Hou, Po-Nien; Hung, Guang-Uei

    2014-01-01

    Conventional dual-head single photon emission computed tomography (SPECT)/CT systems capable of fast dynamic SPECT (DySPECT) imaging have a potential for flow quantitation. This study introduced a new method to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) with DySPECT scan and evaluated the diagnostic performance of detecting coronary artery disease (CAD) compared with perfusion using invasive coronary angiography (CAG) as the reference standard. This study included 21 patients with suspected or known CAD who had received DySPECT, ECG-gated SPECT (GSPECT), and CAG (13 with ≥50 % stenosis in any vessel; non-CAD group: 8 with patent arteries or 99m Tc-sestamibi (MIBI) tracer at rest or dipyridamole-stress stages. DySPECT images were reconstructed with full physical corrections and converted to the physical unit of becquerels per milliliter. Stress MBF (SMBF), rest MBF (RMBF), and MFR were quantified by a one-tissue compartment flow model using time-activity curves derived from DySPECT images. Perfusion images were processed for GSPECT scan and interpreted to obtain summed stress score (SSS) and summed difference score (SDS). Receiver-operating characteristic (ROC) analyses were conducted to evaluate the diagnostic performance of flow and perfusion. Using the criteria of ≥50 % stenosis as positive CAD, areas under the ROC curve (AUCs) of flow assessment were overall significantly greater than those of perfusion. For patient-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.91 ± 0.07, 0.86 ± 0.09, 0.64 ± 0.12, and 0.59 ± 0.13. For vessel-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.81 ± 0.05, 0.76 ± 0.06, 0.62 ± 0.07, and 0.56 ± 0.08, respectively. The preliminary data suggest that MBF quantitation with a conventional SPECT/CT system and the flow quantitation method is a clinically effective approach to enhance CAD detection. (orig.)

  6. Effect of simultaneous application of postural techniques and expiratory muscle strength training on the enhancement of the swallowing function of patients with dysphagia caused by parkinson?s disease

    OpenAIRE

    Byeon, Haewon

    2016-01-01

    [Purpose] This study aimed to investigate the effect of simultaneous application of postural techniques and expiratory muscle strength training on the enhancement of the swallowing function of patients with dysphagia caused by Parkinson?s disease. [Subjects and Methods] The subjects of this study were 18 patients who received simultaneous application of postural techniques and expiratory muscle strength training and 15 patients who received expiratory muscle strength training only. Postural t...

  7. Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

    Science.gov (United States)

    Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander

    2018-04-01

    Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for

  8. Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

    DEFF Research Database (Denmark)

    Zuber, Verena; Bettella, Francesco; Witoelar, Aree

    2017-01-01

    progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC...

  9. Plasma exchange combined with azathioprine in multiple sclerosis using serial gadolinium-enhanced MRI to monitor disease activity: a randomized single-masked cross-over pilot study

    DEFF Research Database (Denmark)

    Sørensen, P.S.; Wanscher, B; Szpirt, W

    1996-01-01

    the whole trial, and three patients discontinued the trial, two during the run-in period of azathioprine treatment and one at the introduction of PE. The primary efficacy variables were the number of gadolinium-enhancing lesions and the occurrence of new enhancing lesions on serial MRI performed every 3...... in the two periods. Although the total MS lesion load on MRI was significantly lower (p beneficial effect of PE or encourage a subsequent large...

  10. Small (≤ 2 cm) hepatocellular carcinoma in patients with chronic liver disease: comparison of gadoxetic acid-enhanced 3.0 T MRI and multiphasic 64-multirow detector CT.

    Science.gov (United States)

    Hwang, J; Kim, S H; Lee, M W; Lee, J Y

    2012-07-01

    To compare the diagnostic performance of gadoxetic acid-enhanced MRI using 3.0 T with that of multiphasic 64-multirow detector CT (MDCT) for the detection of small (≤2 cm) hepatocellular carcinoma (HCC) in patients with chronic liver disease. A total of 54 patients (44 men, 10 women; age range, 33-81 years) with 59 HCCs (≤2 cm in diameter) who underwent both multiphasic (arterial, portal venous, equilibrium) 64-MDCT and gadoxetic acid-enhanced 3.0 T MRI were enrolled in this study. Two observers independently and randomly reviewed the MR and CT images on a lesion-by-lesion basis. The diagnostic performance of these techniques for the detection of HCC was assessed by alternative free-response receiver operating characteristic (ROC) analysis, in addition to evaluating the sensitivity and positive predictive value. For each observer, the areas under the ROC curve were 0.874 and 0.863 for MRI, respectively, as opposed to 0.660 and 0.687 for CT, respectively. The differences between the two techniques were statistically significant for each observer (p0.05). Gadoxetic acid-enhanced 3.0 T MRI shows a better diagnostic performance than that of 64-MDCT for the detection of small (≤2 cm) HCCs in patients with chronic liver disease.

  11. Increased accumulation of 4-hydroxynonenal adducts in female GSTA4/PPAR alpha double knockout mice enhance steatosis and inflammation in a model of pediatric nonalcoholic fatty liver disease

    Science.gov (United States)

    Hepatocellular injury resulting from increased lipid peroxidation products and oxidative stress is considered a potential mechanism driving the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitsis (NASH). To test the significance of lipid peroxidation and protein...

  12. Intranasal PRGF-Endoret enhances neuronal survival and attenuates NF-κB-dependent inflammation process in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Orive, Gorka; Carro, Eva

    2015-04-10

    Parkinson's disease is a common neurodegenerative disorder of unknown pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Oxidative stress, microglial activation and inflammatory responses seem to contribute to the pathogenesis. Recent data showed that growth factors mediate neuroprotection in rodent models of Parkinson's disease, modulating pro-inflammatory processes. Based on our recent studies showing that plasma rich in growth factors (PRGF-Endoret) mediates neuroprotection as inflammatory moderator in Alzheimer's disease, in the present study we examined the effects of plasma rich in growth factors (PRGF-Endoret) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse as a translational therapeutic approach for Parkinson's disease. We found substantial neuroprotection by PRGF-Endoret in our model of Parkinson's disease, which resulted in diminished inflammatory responses and improved motor performance. Additionally, these effects were associated with robust reduction in nuclear transcription factor-κB (NF-κB) activation, and nitric oxide (NO), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) expression in the substantia nigra. We propose that PRGF-Endoret can prevent dopaminergic degeneration via an NF-κB-dependent signaling process. As the clinical safety profile of PRGF-Endoret is already established, these data suggest that PRGF-Endoret provides a novel neuroprotective strategy for Parkinson's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Hericium caput-medusae (Bull.:Fr.) Pers. polysaccharide enhance innate immune response, immune-related genes expression and disease resistance against Aeromonas hydrophila in grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Gou, Changlong; Wang, Jiazhen; Wang, Yuqiong; Dong, Wenlong; Shan, Xiaofeng; Lou, Yujie; Gao, Yunhang

    2018-01-01

    The objective was to add 0, 400, 800 or 1200 mg/kg of Hericium caput-medusae polysaccharide (HCMP) to the basal diet of grass carp (Ctenopharyngodon idella) and determine effects on humoral innate immunity, expression of immune-related genes and disease resistance. Adding HCMP enhanced (P < 0.05) bactericidal activity at 1, 2 and 3 weeks and also lysozyme activity, complement C3, and SOD activity at 2 and 3 weeks. Supplementing 800 or 1200 mg/kg of HCMP for 2 or 3 weeks increased (P < 0.05) serum concentrations of total protein, albumin and globulin. Two immune-related genes (IL-1β and TNF-α) were up-regulated (P < 0.05) in HCMP supplemented groups given 800 or 1200 mg/kg HCMP after 2 and 3 weeks of feeding. Expression of anti-inflammatory cytokine IL-10 was down-regulated (P < 0.05) after receiving 800 or 1200 mg/kg HCMP for 2 or 3 weeks. Fish fed 800 mg/kg HCMP had maximal disease resistance against Aeromonas hydrophila (65.4%). In conclusion, HCMP enhanced immune response and expression of immune-related genes and increased disease resistance against Aeromonas hydrophila in grass carp, with greatest effects in fish given 800 mg/kg HCMP for 3 weeks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Enhanced CT in the diagnosis of acute appendicitis to evaluate the severity of disease. Comparison of CT findings and histological diagnosis

    International Nuclear Information System (INIS)

    Mori, Yoshiko; Yamasaki, Michio; Furukawa, Akira; Takahashi, Masashi; Murata, Kiyoshi

    2001-01-01

    To assess the potential of CT in evaluating the histological severity of acute appendicitis in comparison with surgical and pathological findings. The CT images of 75 patients with surgically proven appendicitis, including 10 cases of catarrhal, 34 of phlegmonous, and 31 of gangrenous appendicitis, were retrospectively analyzed for the following five CT findings: hazy periappendiceal densities, enlarged appendix, increased enhancement of the appendiceal wall, increased enhancement of the periappendiceal intestinal wall, and deficiency of the appendiceal wall. By comparing all the CT findings and the pathological severity of appendicitis (catarrhal, phlegmonous, and gangrenous), the prevalence of the five CT findings was calculated for each pathological category. Abnormal CT findings were noted in only one case of catarrhal appendicitis. Increased enhancement of the appendiceal wall was observed in all 29 cases of phlegmonous appendicitis (100%), but in only 66.7% (18 cases) of gangrenous appendicitis. Deficiency of the appendiceal wall was more frequently observed in gangrenous (19/27, 70.4%) than phlegmonous appendicitis (4/29, 13.8%). Findings of enhanced CT provide useful information in evaluating the pathological severity of acute appendicitis. (author)

  15. Why looking at the whole hippocampus is not enough – a critical role for anteroposterior axis, subfield and activation analyses to enhance predictive value of hippocampal changes for Alzheimer’s disease diagnosis.

    Directory of Open Access Journals (Sweden)

    Aleksandra eMaruszak

    2014-03-01

    Full Text Available The hippocampus is one of the earliest affected brain regions in Alzheimer´s disease (AD and its dysfunction is believed to underlie the core feature of the disease- memory impairment. Given that hippocampal volume is one of the best AD biomarkers, our review focuses on distinct subfields within the hippocampus, pinpointing regions that might enhance the predictive value of current diagnostic methods. Our review presents how changes in hippocampal volume, shape, symmetry and activation are reflected by cognitive impairment and how they are linked with neurogenesis alterations. Moreover, we revisit the functional differentiation along the anteroposterior longitudinal axis of the hippocampus and discuss its relevance for AD diagnosis. Finally, we indicate that apart from hippocampal subfield volumetry, the characteristic pattern of hippocampal hyperactivation associated with seizures and neurogenesis changes is another promising candidate for an early AD biomarker that could become also a target for early interventions.

  16. Building a foundation for 'One Health': an education strategy for enhancing and sustaining national and regional capacity in endemic and emerging zoonotic disease management.

    Science.gov (United States)

    Vink, W D; McKenzie, Joanna S; Cogger, Naomi; Borman, Barry; Muellner, Petra

    2013-01-01

    The rapid global spread of diseases such as SARS, H5N1, and H1N1 influenza has emphasized the pressing need for trans-disciplinary collaboration and cross-border action, and has also exposed a serious deficit of capacity and coordination in dealing effectively with emerging disease threats. The need for capacity development is particularly acute in the developing world, which is the least well-equipped to respond adequately. Such capacity development can be achieved through education and the implementation of applied 'One Health' activities. This chapter describes the establishment of a 'One Health' capacity development program in South Asia, consisting of two phases. The first phase provides Masters level training for public health doctors and veterinarians, with a focus on epidemiology, and disease control. The second phase reinforces the postgraduate training by establishing a sustainable framework for the implementation of collaborative 'One Health' activities such as the development of multidisciplinary professional networks, implementation of applied zoonotic disease investigation projects, and support for continuing professional development. The objectives are to provide individual skills required to strengthen capacity; to develop an appreciation of the cross-cutting issues which affect human and animal health, set within an institutional context; and to facilitate the development of regional professional networks which will be instrumental in implementing 'One Health' activities.

  17. The combination of nutraceutical and simvastatin enhances the effect of simvastatin alone in normalising lipid profile without side effects in patients with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Giuseppe Campolongo

    2016-06-01

    Conclusions: The association of a nutraceutical and simvastatin 20 mg may be a valid therapeutic option for the treatment of hyperlipidemia in patients with ischemic heart disease intolerant to statin at high doses, in the absence of side effects. Further studies are needed to clarify the mechanisms of action of nutraceuticals.

  18. A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent

    NARCIS (Netherlands)

    Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; Deponte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J. T. H.; van Dam, Alje P.; van der Poll, Tom; van't Veer, Cornelis; Hovius, Joppe W.; Fikrig, Erol

    2011-01-01

    The Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8, which reduced

  19. Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Kranenburg, A. R.; de Boer, W. I.; Alagappan, V. K. T.; Sterk, P. J.; Sharma, H. S.

    2005-01-01

    BACKGROUND: Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in tissue remodelling and

  20. Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    A.R. Kranenburg (Andor); W.I. de Boer (Pim); V.K.T. Alagappan (Vijay Kumar Thyagarajan); P.J. Sterk (Peter); H.S. Sharma (Hari)

    2005-01-01

    textabstractBACKGROUND: Ongoing inflammatory processes resulting in airway and vascular remodelling characterise chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1) could play a role in

  1. The Heterologous Expression of the p22 RNA Silencing Suppressor of the Crinivirus Tomato Chlorosis Virus from Tobacco Rattle Virus and Potato Virus X Enhances Disease Severity but Does Not Complement Suppressor-Defective Mutant Viruses.

    Science.gov (United States)

    Landeo-Ríos, Yazmín; Navas-Castillo, Jesús; Moriones, Enrique; Cañizares, M. Carmen

    2017-11-24

    To counteract host antiviral RNA silencing, plant viruses express suppressor proteins that function as pathogenicity enhancers. The genome of the Tomato chlorosis virus (ToCV) (genus Crinivirus , family Closteroviridae ) encodes an RNA silencing suppressor, the protein p22, that has been described as having one of the longest lasting local suppressor activities when assayed in Nicotiana benthamiana . Since suppression of RNA silencing and the ability to enhance disease severity are closely associated, we analyzed the effect of expressing p22 in heterologous viral contexts. Thus, we studied the effect of the expression of ToCV p22 from viral vectors Tobacco rattle virus (TRV) and Potato virus X (PVX), and from attenuated suppressor mutants in N. benthamiana plants. Our results show that although an exacerbation of disease symptoms leading to plant death was observed in the heterologous expression of ToCV p22 from both viruses, only in the case of TRV did increased viral accumulation occur. The heterologous expression of ToCV p22 could not complement suppressor-defective mutant viruses.

  2. ENHANCING VACCINAL PREVENTION OF THE HUMAN PAPILLOMA VIRAL (HPV INFECTION: PROTECTING PEOPLE OF DIFFERENT AGE AND SEX FROM A RANGE OF HPV-ASSOCIATED DISEASES

    Directory of Open Access Journals (Sweden)

    M. G. Galitskaya

    2013-01-01

    Full Text Available HPV is the most widespread sexually transmitted infection. HPV affects men and women regardless of age and leads to the development of various anogenital area diseases. International studies proved a wide clinical range of the tetravalent HPV vaccine protection and allowed recommending it for the prevention of not only cervical cancer, but also of vulvar, vaginal and anal cancer and anogenital condylomae in patients of both sexes. 42 countries have already introduced national HPV-vaccination programs in compliance with WHO recommendations. Anogenital area cancer morbidity reduction in these countries is expected in 10-15 years. However, a reduction or even complete disappearance of anogenital condylomae among the population has already been noted in a range of countries because the incubation period of this disease is short; this is the first marker of vaccination efficacy in a population.

  3. Achieving best outcomes for patients with cardiovascular disease in China by enhancing the quality of medical care and establishing a learning health-care system.

    Science.gov (United States)

    Jiang, Lixin; Krumholz, Harlan M; Li, Xi; Li, Jing; Hu, Shengshou

    2015-10-10

    China has an immediate need to address the rapidly growing population with cardiovascular disease events and the increasing number of people living with this illness. Despite progress in increasing access to services, China faces the dual challenge of addressing gaps in quality of care and producing more evidence to support clinical practice. In this Review, we address opportunities to strengthen performance measurement, programmes to improve quality of care, and national capacity to produce high-impact knowledge for clinical practice. Moreover, we propose recommendations, with implications for other diseases, for how China can immediately make use of its Hospital Quality-Monitoring System and other existing national platforms to assess and improve performance of medical care, and to generate new knowledge to inform clinical decisions and national policies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. PPARGC1A/PGC-1α, TFEB and enhanced proteostasis in Huntington disease: Defining regulatory linkages between energy production and protein–organelle quality control

    OpenAIRE

    La Spada, Albert R.

    2012-01-01

    Huntington disease (HD) results from CAG repeats that encode expanded polyglutamine tracts in the HTT/huntingtin protein. HD belongs to a large category of inherited and sporadic neurodegenerative disorders in which production of a misfolded protein initiates the pathogenic cascade. Previous studies have shown that misfolded proteins become resistant to cellular protein turnover pathways by eluding and disabling the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway. Based upon ...

  5. Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

    Science.gov (United States)

    Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

    2017-06-15

    The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel

  6. A national evaluation of a dissemination and implementation initiative to enhance primary care practice capacity and improve cardiovascular disease care: the ESCALATES study protocol

    OpenAIRE

    Cohen, Deborah J.; Balasubramanian, Bijal A.; Gordon, Leah; Marino, Miguel; Ono, Sarah; Solberg, Leif I.; Crabtree, Benjamin F.; Stange, Kurt C.; Davis, Melinda; Miller, William L.; Damschroder, Laura J.; McConnell, K. John; Creswell, John

    2016-01-01

    Background The Agency for Healthcare Research and Quality (AHRQ) launched the EvidenceNOW Initiative to rapidly disseminate and implement evidence-based cardiovascular disease (CVD) preventive care in smaller primary care practices. AHRQ funded eight grantees (seven regional Cooperatives and one independent national evaluation) to participate in EvidenceNOW. The national evaluation examines quality improvement efforts and outcomes for more than 1500 small primary care practices (restricted to...

  7. VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease.

    Science.gov (United States)

    Díaz-Alonso, Javier; Paraíso-Luna, Juan; Navarrete, Carmen; Del Río, Carmen; Cantarero, Irene; Palomares, Belén; Aguareles, José; Fernández-Ruiz, Javier; Bellido, María Luz; Pollastro, Federica; Appendino, Giovanni; Calzado, Marco A; Galve-Roperh, Ismael; Muñoz, Eduardo

    2016-07-19

    Cannabinoids have shown to exert neuroprotective actions in animal models by acting at different targets including canonical cannabinoid receptors and PPARγ. We previously showed that VCE-003, a cannabigerol (CBG) quinone derivative, is a novel neuroprotective and anti-inflammatory cannabinoid acting through PPARγ. We have now generated a non-thiophilic VCE-003 derivative named VCE-003.2 that preserves the ability to activate PPARγ and analyzed its neuroprotective activity. This compound exerted a prosurvival action in progenitor cells during neuronal differentiation, which was prevented by a PPARγ antagonist, without affecting neural progenitor cell proliferation. In addition, VCE-003.2 attenuated quinolinic acid (QA)-induced cell death and caspase-3 activation and also reduced mutant huntingtin aggregates in striatal cells. The neuroprotective profile of VCE-003.2 was analyzed using in vivo models of striatal neurodegeneration induced by QA and 3-nitropropionic acid (3NP) administration. VCE-003.2 prevented medium spiny DARPP32(+) neuronal loss in these Huntington's-like disease mice models improving motor deficits, reactive astrogliosis and microglial activation. In the 3NP model VCE-003.2 inhibited the upregulation of proinflammatory markers and improved antioxidant defenses in the brain. These data lead us to consider VCE-003.2 to have high potential for the treatment of Huntington's disease (HD) and other neurodegenerative diseases with neuroinflammatory traits.

  8. Enhancement of a locally developed HIV prevention intervention for Hispanic/Latino MSM: A partnership of community-based organizations, a university, and the Centers for Disease Control and Prevention

    Science.gov (United States)

    Rhodes, Scott D.; Alonzo, Jorge; Mann, Lilli; Freeman, Arin; Sun, Christina J.; Garcia, Manuel; Painter, Thomas M.

    2015-01-01

    Hispanic/Latino men who have sex with men (MSM) in the United States are disproportionately affected by HIV and other sexually transmitted diseases (STDs); however, no efficacious behavioral interventions are currently available for use with this vulnerable population. We describe the development and enhancement of HOLA en Grupos, a community-based behavioral HIV/STD prevention intervention for Spanish-speaking Hispanic/Latino MSM that is currently being implemented and evaluated. Our enhancement process included incorporating local data on risks and context; identifying community priorities; defining intervention core elements and key characteristics; developing a logic model; developing an intervention logo; enhancing intervention activities and materials; scripting intervention delivery; expanding the comparison intervention; and establishing a materials review committee. If efficacious, HOLA en Grupos will be the first behavioral intervention to be identified for potential use with Hispanic/Latino MSM, thereby contributing to the body of evidence-based resources that may be used for preventing HIV/STD infection among these MSM and their sex partners. PMID:26241382

  9. Malignant focal hepatic lesions complicating underlying liver disease: dual-phase contrast-enhanced spiral CT sensitivity and specificity in orthotopic liver transplant patients

    International Nuclear Information System (INIS)

    Mortele, K.J.; De Keukeleire, K.; Praet, M.; Van Vlierberghe, H.; Hemptinne, B. de; Ros, P.R.

    2001-01-01

    The aim of this study was to determine the accuracy of contrast-enhanced biphasic spiral CT as a screening tool in the preoperative evaluation of orthotopic liver transplant (OLT) patients. Spiral-CT examinations were performed before liver transplantation in 53 patients. Scans were retrospectively reviewed and compared with pathologic findings in fresh-sectioned livers. When findings between spiral CT and pathology were discordant, formalized livers were reexamined with lesion-by lesion evaluation. Fresh pathologic evaluation revealed 23 liver lesions (16 HCC, 7 macro-regenerative nodules). Malignancy was identified in 13 of 53 patients (24.5%). Pre-transplantation spiral CT depicted 27 liver lesions (23 HCC, 4 macro-regenerative nodules). Malignancy was suspected in 14 patients (26.4%). In 10 of 53 (18.9%), spiral CT and pathologic evaluation were discordant. Subsequent retrospective pathologic evaluation showed malignancy in 4 additional patients. Spiral CT compared with the retrospective pathologic findings revealed 36 real-negative, 14 real-positive, 0 false-positive, and 3 false-negative patients with malignancy. Sensitivity and specificity of spiral CT in detection of malignancy was 82 and 100%, respectively. Contrast-enhanced biphasic spiral CT is an accurate technique in the evaluation of patients preceding OLT. Routine fresh-sectioned liver pathologic findings are not as sensitive as previously estimated. (orig.)

  10. Pokémon-Go: Why Augmented Reality Games Offer Insights for Enhancing Public Health Interventions on Obesity-Related Diseases.

    Science.gov (United States)

    Wong, Ming Chao; Turner, Paul; MacIntyre, Kate; Yee, Kwang Chien

    2017-01-01

    Stimulating widespread interests of the population to participate in behavioural changes through information and technology has been an aim of much health informatics research. The recent widespread participation of the augmented reality game Pokémon Go which encourages exercises, provides significant insights into the potential of information technology to improve healthcare intervention on obesity-related disease. Does Pokémon Go point to another way of achieving health benefits using mobile devices? This paper analyses the features of Pokémon Go in relation to potential health benefits. This paper suggests from the perspective of a user on changes to the game that potentially could help with obesity, mental health cardiovascular health and vitamin D deficiencies. While the impact of augmented reality games on improving exercises might be substantial, the question of sustainability and likely long-term health outcomes remain debatable. The rapid uptake of Pokémon Go by the population around the world, however, should serve as a useful lesson f