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Sample records for disease progression monitoring

  1. Weight preserving image registration for monitoring disease progression in lung CT.

    Science.gov (United States)

    Gorbunova, Vladlena; Lol, Pechin; Ashraf, Haseem; Dirksen, Asger; Nielsen, Mads; de Bruijne, Marleen

    2008-01-01

    We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan compared with intensities in the deformed baseline image indicate local loss of lung tissue that is associated with progression of emphysema. To account for differences in lung intensity owing to differences in the inspiration level in the two scans rather than disease progression, we propose to adjust the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans and may result in a more sensitive measure of disease progression than standard quantitative CT measures.

  2. Weight preserving image registration for monitoring disease progression in lung CT

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Lo, Pechin Chien Pau; Haseem, Ashraf

    2008-01-01

    We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan...... the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans...

  3. An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li [Department of Pathology, University of Washington, Seattle WA USA; Stewart, Tessandra [Department of Pathology, University of Washington, Seattle WA USA; Shi, Min [Department of Pathology, University of Washington, Seattle WA USA; Pottiez, Gwenael [Department of Pathology, University of Washington, Seattle WA USA; Dator, Romel [Department of Pathology, University of Washington, Seattle WA USA; Wu, Rui [Department of Pathology, University of Washington, Seattle WA USA; Department of Pathology, No. 3 Hospital of Beijing University, Beijing China; Aro, Patrick [Department of Pathology, University of Washington, Seattle WA USA; Schuster, Robert J. [Department of Pathology, University of Washington, Seattle WA USA; Ginghina, Carmen [Department of Pathology, University of Washington, Seattle WA USA; Pan, Catherine [Department of Pathology, University of Washington, Seattle WA USA; Gao, Yuqian [Pacific Northwest National Laboratory, Richland WA USA; Qian, Weijun [Pacific Northwest National Laboratory, Richland WA USA; Zabetian, Cyrus P. [Parkinson' s Disease Research and Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle WA USA; Department of Neurology, University of Washington School of Medicine, Seattle WA USA; Hu, Shu-Ching [Department of Neurology, University of Washington School of Medicine, Seattle WA USA; Quinn, Joseph F. [Department of Neurology, Oregon Health and Science University, Portland OR USA; Zhang, Jing [Department of Pathology, University of Washington, Seattle WA USA; Department of Pathology, Peking University Health Science Centre and Third Hospital, Beijing 100083 China

    2017-04-19

    Aim: The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson’s disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, we developed a highly sensitive Multiple Reaction Monitoring (MRM) method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers. Results: Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally. Conclusions: An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger-scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression.

  4. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I

    DEFF Research Database (Denmark)

    Willis, Tracey A; Hollingsworth, Kieren G; Coombs, Anna

    2013-01-01

    Outcome measures for clinical trials in neuromuscular diseases are typically based on physical assessments which are dependent on patient effort, combine the effort of different muscle groups, and may not be sensitive to progression over short trial periods in slow-progressing diseases. We hypoth...

  5. Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

    Science.gov (United States)

    Song, Gaoguang; Liu, Yujie; Wang, Yanying; Ren, Guanjun; Guo, Shuai; Ren, Junling; Zhang, Li; Li, Zhili

    2015-02-02

    Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression. Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis. Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks). The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study.

    Directory of Open Access Journals (Sweden)

    Tracey A Willis

    Full Text Available Outcome measures for clinical trials in neuromuscular diseases are typically based on physical assessments which are dependent on patient effort, combine the effort of different muscle groups, and may not be sensitive to progression over short trial periods in slow-progressing diseases. We hypothesised that quantitative fat imaging by MRI (Dixon technique could provide more discriminating quantitative, patient-independent measurements of the progress of muscle fat replacement within individual muscle groups.To determine whether quantitative fat imaging could measure disease progression in a cohort of limb-girdle muscular dystrophy 2I (LGMD2I patients over a 12 month period.32 adult patients (17 male;15 female from 4 European tertiary referral centres with the homozygous c.826C>A mutation in the fukutin-related protein gene (FKRP completed baseline and follow up measurements 12 months later. Quantitative fat imaging was performed and muscle fat fraction change was compared with (i muscle strength and function assessed using standardized physical tests and (ii standard T1-weighted MRI graded on a 6 point scale.There was a significant increase in muscle fat fraction in 9 of the 14 muscles analyzed using the quantitative MRI technique from baseline to 12 months follow up. Changes were not seen in the conventional longitudinal physical assessments or in qualitative scoring of the T₁w images.Quantitative muscle MRI, using the Dixon technique, could be used as an important longitudinal outcome measure to assess muscle pathology and monitor therapeutic efficacy in patients with LGMD2I.

  7. Progression of Liver Disease

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  8. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

    Science.gov (United States)

    Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

    2015-01-01

    Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

  9. In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

    International Nuclear Information System (INIS)

    Inoue, Yusuke; Okubo, Toshiyuki; Tojo, Arinobu; Sekine, Rieko; Soda, Yasushi; Kobayashi, Seiichiro; Nomura, Akiko; Izawa, Kiyoko; Kitamura, Toshio; Ohtomo, Kuni

    2006-01-01

    The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity. (orig.)

  10. Value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection

    Directory of Open Access Journals (Sweden)

    BAO Teng

    2017-08-01

    Full Text Available ObjectiveTo investigate the clinical value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection. MethodsA retrospective analysis was performed for the clinical data of 1107 patients with different clinical stages of chronic HBV infection who had not received antiviral therapy at the time of hospitalization in The Second Affiliated Hospital of Anhui Medical University from May 2011 to December 2015, and according to the disease status, they were divided into HBeAg-positive chronic hepatitis B (CHB group, HBeAg-negative CHB group, compensated liver cirrhosis group (LC-C group, decompensated liver cirrhosis group (LC-D group, and primary liver cancer (PLC group. These groups were compared in terms of HBsAg expression and the association between HBsAg and clinical features. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between any two groups; the t-test was used for comparison of continuous data between two groups. The chi-square test was used for comparison of categorical data between these groups. Pearson correlation analysis was also performed. ResultsThere was a significant difference in serum HBsAg level between the HBeAg-positive CHB group, HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=100.45, P<0.001. The HBeAg-positive CHB group had significantly higher levels of HBsAg and HBV DNA than the HBeAg-negative CHB group (t= 16.67 an 16.22, both P<0.001. There were significant differences in HBsAg and HBV DNA levels between the HBeAg-positive CHB group, LC-C group, LC-D group, and PLC group (F= 42.92 and 27.38, both P<0.001, as well as between the HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=6.04 and 4.10, both P<0.05. HBV DNA level was significantly different across patients with different HBsAg levels (<1000 IU/ml, 1000-20 000 IU

  11. Monitoring Students' Academic & Disciplinary Progression.

    Science.gov (United States)

    McDonald, Fred; Kellogg, Larry J.

    This document outlines the objectives and procedures of a program at a New Mexico school district whose purpose is to enable school personnel to systematically monitor students' academic and disciplinary progression. The objectives of the program are to diagnose academic or disciplinary problems and prescribe remedies, to establish an oncampus…

  12. En Face Spectral-Domain Optical Coherence Tomography for the Monitoring of Lesion Area Progression in Stargardt Disease.

    Science.gov (United States)

    Melillo, Paolo; Testa, Francesco; Rossi, Settimio; Di Iorio, Valentina; Orrico, Ada; Auricchio, Alberto; Simonelli, Francesca

    2016-07-01

    We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best-corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials.

  13. En Face Spectral-Domain Optical Coherence Tomography for the Monitoring of Lesion Area Progression in Stargardt Disease

    Science.gov (United States)

    Melillo, Paolo; Testa, Francesco; Rossi, Settimio; Di Iorio, Valentina; Orrico, Ada; Auricchio, Alberto; Simonelli, Francesca

    2016-01-01

    Purpose We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT). Methods We reviewed medical records of STGD1 patients, with a clinical and molecular diagnosis of STGD1 at a single institution, who underwent best-corrected visual acuity (BCVA), fundus photography, SD-OCT, full-field electroretinography, and, when available, fundus autofluorescence (FAF). Regression models were fitted on the selected clinical parameters; in particular, on the macular lesion area computed by SD-OCT, to evaluate the disease progression over a multiyear follow-up. Results The comparison between SD-OCT and FAF, available for 22 patients, showed that macular lesion area, assessed by SD-OCT, significantly correlated with the area of absent FAF (P disease, showing a significant progression over the follow-up. Our findings suggest that the evaluation of macular lesion area by en face SD-OCT, together with FAF, could drive the choice of the most amenable candidates and the most suitable area to be treated in gene therapy clinical trials. PMID:27409479

  14. Geothermal progress monitor. Progress report No. 1

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    Progress is reported on the following: electrical uses, direct-heat uses, drilling activities, leases, geothermal loan guarantee program, general activities, and legal, institutional, and regulatory activites. (MHR)

  15. Progression of Liver Disease

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    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now The Progression of Liver ...

  16. The neural basis of monitoring goal progress

    Directory of Open Access Journals (Sweden)

    Yael eBenn

    2014-09-01

    Full Text Available The neural basis of progress monitoring has received relatively little attention compared to other sub-processes that are involved in goal directed behavior such as motor control and response inhibition. Studies of error-monitoring have identified the dorsal anterior cingulate cortex (dACC as a structure that is sensitive to conflict detection, and triggers corrective action. However, monitoring goal progress involves monitoring correct as well as erroneous events over a period of time. In the present research, 20 healthy participants underwent fMRI while playing a game that involved monitoring progress towards either a numerical or a visuo-spatial target. The findings confirmed the role of the dACC in detecting situations in which the current state may conflict with the desired state, but also revealed activations in the frontal and parietal regions, pointing to the involvement of processes such as attention and working memory in monitoring progress over time. In addition, activation of the cuneus was associated with monitoring progress towards a specific target presented in the visual modality. This is the first time that activation in this region has been linked to higher-order processing of goal-relevant information, rather than low-level anticipation of visual stimuli. Taken together, these findings identify the neural substrates involved in monitoring progress over time, and how these extend beyond activations observed in conflict and error monitoring.

  17. Geothermal progress monitor report No. 6

    Energy Technology Data Exchange (ETDEWEB)

    1982-06-01

    Geothermal Progress Monitor Report No. 6 presents a state-by-state summary of the status of geothermal leasing, exploration, and development in major physiographic regions where geothermal resource potential has been identified. Recent state-specific activities are reported at the end of each state status report, while recent activities of a more general nature are summarized briefly in Part II of the report. A list of recent publications of potential interest to the geothermal community and a directory of contributors to the geothermal progress monitoring system are also included.

  18. A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

    Directory of Open Access Journals (Sweden)

    Todd D. Levine

    2012-01-01

    Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

  19. Progression of Late-Onset Stargardt Disease.

    Science.gov (United States)

    Lambertus, Stanley; Lindner, Moritz; Bax, Nathalie M; Mauschitz, Matthias M; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; den Hollander, Anneke I; Weber, Bernhard H F; Holz, Frank G; van der Wilt, Gert Jan; Fleckenstein, Monika; Hoyng, Carel B

    2016-10-01

    Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset ≥ 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high.

  20. Sudden oak death disease progression in oaks and tanoaks

    Science.gov (United States)

    Brice A. McPherson; Sylvia R. Mori; David L. Wood; Andrew J. Storer; Pavel Svihra; N. Maggi Kelly; Richard B. Standiford

    2006-01-01

    In March 2000, we established twenty disease progression plots in Marin County to monitor the progress of sudden oak death symptoms in coast live oak (Quercus agrifolia), California black oak (Q. kelloggii), and tanoak (Lithocarpus densiflorus) (McPherson and others 2005). Plots were located to encompass a...

  1. Early Glucose Derangement Detected by Continuous Glucose Monitoring and Progression of Liver Fibrosis in Nonalcoholic Fatty Liver Disease: An Independent Predictive Factor?

    Science.gov (United States)

    Schiaffini, Riccardo; Liccardo, Daniela; Alisi, Anna; Benevento, Danila; Cappa, Marco; Cianfarani, Stefano; Nobili, Valerio

    2016-01-01

    Glucose derangement has been reported to increase oxidative stress, one of the most important factors underlying the progression of hepatic fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). To date, careful evaluation of the glucose profile in pediatric NAFLD has not been performed. A total of 30 severely obese children (15 males; mean age 12.87 ± 2.19 years) with biopsy-proven NAFLD were enrolled in this study from September to December 2013. All patients underwent anthropometric and laboratory evaluation, including the oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM). Our study reveals some differences between OGTT and CGM in detecting NAFLD children with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). OGTT showed 2 (6.67%) patients with IFG and 1 (3.34%) with IGT, while CGM showed 5 (16.67%) patients with IFG and 6 (20%) with IGT. The daily blood glucose profile positively correlated with the baseline blood glucose (r = 0.39, p = 0.04) and the homeostatic model assessment (r = 0.56, p = 0.05). A positive correlation between hyperglycemia and liver fibrosis was found (r = 0.65, p < 0.05). Mean glucose values (F3-F4 group: 163.2 ± 35.92 mg/dl vs. F1 group: 136.58 ± 46.83 mg/dl and F2 group: 154.12 ± 22.51 mg/dl) and the difference between the minimum and maximum blood glucose levels (F3-F4 group: 110.21 ± 25.26 mg/dl vs. F1 group: 91.67 ± 15.97 mg/dl and F2 group: 92 ± 15.48 mg/dl) were significantly (p < 0.05) higher in the F3-F4 group compared to the F1 and F2 groups. Glucose profile derangement as detected by CGM is associated with the severity of hepatic fibrosis in children with NAFLD. © 2015 S. Karger AG, Basel.

  2. Geothermal Progress Monitor: Report No. 14

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-01

    This issue of the Geothermal Progress Monitor, the 14th since its inception in 1980, highlights the anticipated rapid growth in the use of geothermal heat pumps and documents the continued growth in the use of geothermal energy for power generation, both in this country and abroad. In countries with a relatively large demand for new generation capacity, geothermal, if available, is being called on as a preferable alternative to the use of domestic or imported oil. On the other hand, in this country where current demand for new capacity is less, geothermal energy is commonly being put to use in small power generation units operating on the hot water resource.

  3. Geothermal Progress Monitor. Report No. 15

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-01

    Two themes dominate this issue of the Geothermal Progress Monitor, the 15th since its inception in 1980. The first of these is the significance of the government/industry partnership role in geothermal development. This joint effort is reflected in the continued, measured growth in the use of geothermal energy, for both power generation and direct use applications, in this country and abroad, as well as in the development of new, innovative technologies to ensure a bright future for the resource. The second theme is the growing popularity of geothermal heat pumps (GHPs) among utilities, their customers, and federal agencies, all with disparate interests in the technology.

  4. Progression of motor symptoms in Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Ruiping Xia; Zhi-Hong Mao

    2012-01-01

    Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity,bradykinesia and tremor - due to loss of dopaminergic neurons.The motor symptoms of PD become progressively worse as the disease advances.PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others.In recent years,many studies have investigated the progression of the hallmark symptoms over time,and the cardinal motor symptoms have different rates of progression,with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor.The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability.Increasing the dosage of dopaminergic medication is commonly used to combat the worsenirtg symptoms.However,the drug-induced involuntary body movements and motor comphcations can significantly contribute to overall disability.Further,none of the currently-available therapies can slow or halt the disease progression.Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression.In this article,the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.

  5. Crevicular fluid biomarkers and periodontal disease progression.

    Science.gov (United States)

    Kinney, Janet S; Morelli, Thiago; Oh, Min; Braun, Thomas M; Ramseier, Christoph A; Sugai, Jim V; Giannobile, William V

    2014-02-01

    Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Progress in genetics of coronary artery disease

    African Journals Online (AJOL)

    Radwa Gamal

    To the Editor. Coronary Heart Disease (CHD) is the leading cause of mortality and morbidity worldwide [1] and it is a result of coronary artery disease (CAD). Coronary artery disease refers to the build-up of atherosclerotic plaque in the blood vessels that supply oxygen and nutrients to the heart. Progressive infiltration of the ...

  7. Automatic total kidney volume measurement on follow-up magnetic resonance images to facilitate monitoring of autosomal dominant polycystic kidney disease progression.

    Science.gov (United States)

    Kline, Timothy L; Korfiatis, Panagiotis; Edwards, Marie E; Warner, Joshua D; Irazabal, Maria V; King, Bernard F; Torres, Vicente E; Erickson, Bradley J

    2016-02-01

    Renal imaging examinations provide high-resolution information about the anatomic structure of the kidneys and are used to measure total kidney volume (TKV) in autosomal dominant polycystic kidney disease (ADPKD) patients. TKV has become the gold-standard image biomarker for ADPKD progression at early stages of the disease and is used in clinical trials to characterize treatment efficacy. Automated methods to segment the kidneys and measure TKV are desirable because of the long time requirement for manual approaches such as stereology or planimetry tracings. However, ADPKD kidney segmentation is complicated by a number of factors, including irregular kidney shapes and variable tissue signal at the kidney borders. We describe an image processing approach that overcomes these problems by using a baseline segmentation initialization to provide automatic segmentation of follow-up scans obtained years apart. We validated our approach using 20 patients with complete baseline and follow-up T1-weighted magnetic resonance images. Both manual tracing and stereology were used to calculate TKV, with two observers performing manual tracings and one observer performing repeat tracings. Linear correlation and Bland-Altman analysis were performed to compare the different approaches. Our automated approach measured TKV at a level of accuracy (mean difference ± standard error = 0.99 ± 0.79%) on par with both intraobserver (0.77 ± 0.46%) and interobserver variability (1.34 ± 0.70%) of manual tracings. All approaches had excellent agreement and compared favorably with ground-truth manual tracing with interobserver, stereological and automated approaches having 95% confidence intervals ∼ ± 100 mL. Our method enables fast, cost-effective and reproducible quantification of ADPKD progression that will facilitate and lower the costs of clinical trials in ADPKD and other disorders requiring accurate, longitudinal kidney quantification. In addition, it will hasten the routine use of

  8. Monitoring and treatment of diseases

    NARCIS (Netherlands)

    Ronyai, A.; Gielen, M.; Philipsen, E.; Kamstra, A.

    2003-01-01

    Early recognition and efficient treatment of diseases are important factors for the success of any fish farming operation. Experience learns that during the culture of a new species like pikeperch (partly in new systems) new disease problems will be encountered. The subtask on monitoring and

  9. Geothermal Progress Monitor. Report No. 18

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The near-term challenges of the US geothermal industry and its long-range potential are dominant themes in this issue of the US Department of Energy (DOE) Geothermal Progress Monitor which summarizes calendar-year 1996 events in geothermal development. Competition is seen as an antidote to current problems and a cornerstone of the future. Thus, industry's cost-cutting strategies needed to increase the competitiveness of geothermal energy in world markets are examined. For example, a major challenge facing the US industry today is that the sales contracts of independent producers have reached, or soon will, the critical stage when the prices utilities must pay them drop precipitously, aptly called the cliff. However, Thomas R. Mason, President and CEO of CalEnergy told the DOE 1996 Geothermal Program Review XIV audience that while some of his company's plants have ''gone over the cliff, the world is not coming to an end.'' With the imposition of severe cost-cutting strategies, he said, ''these plants remain profitable... although they have to be run with fewer people and less availability.'' The Technology Development section of the newsletter discusses enhancements to TOUGH2, the general purpose fluid and heat flow simulator and the analysis of drill cores from The Geysers, but the emphasis is on advanced drilling technologies.

  10. Geothermal Progress Monitor report No. 11

    Energy Technology Data Exchange (ETDEWEB)

    1989-12-01

    This issue of the Geothermal Progress Monitor (GPM) is the 11th since the inception of the publication in 1980. It continues to synthesize information on all aspects of geothermal development in this country and abroad to permit identification and quantification of trends in the use of this energy technology. In addition, the GPM is a mechanism for transferring current information on geothermal technology development to the private sector, and, over time, provides a historical record for those interested in the development pathway of the resource. In sum, the Department of Energy makes the GPM available to the many diverse interests that make up the geothermal community for the multiple uses it may serve. This issue of the GPM points up very clearly how closely knit many of those diverse interests have become. It might well be called an international issue'' since many of its pages are devoted to news of geothermal development abroad, to the efforts of the US industry to participate in overseas development, to the support given those efforts by federal and state agencies, and to the formation of the International Geothermal Association (IGA). All of these events indicate that the geothermal community has become truly international in character, an occurrence that can only enhance the future of geothermal energy as a major source of energy supply worldwide. 15 figs.

  11. Geothermal Progress Monitor, report No. 13

    Energy Technology Data Exchange (ETDEWEB)

    1992-02-01

    Geothermal Progress Monitor (GPM) Issue No. 13 documents that most related factors favor the growth and geographic expansion of the US geothermal industry and that the industry is being technologically prepared to meet those challenges into the next century. It is the function of GPM to identify trends in the use of this resource and to provide a historical record of its development pathway. The information assembled for this issue of GPM indicates that trends in the use of geothermal energy in this country and abroad continue to be very positive. Favorable sentiments as well as pertinent actions on the part of both government and industry are documented in almost every section. The FEDERAL BEAT points up that the National Energy Strategy (NES) developed at the highest levels of the US government recognizes the environmental and energy security advantages of renewable energy, including geothermal, and makes a commitment to substantial diversification'' of US sources of energy. With the announcement of the construction of several new plants and plant expansions, the INDUSTRY SCENE illustrates industry's continued expectation tha the use of geothermal energy will prove profitable to investors. In DEVELOPMENT STATUS, spokesmen for both an investor-owned utility and a major geothermal developer express strong support for geothermal power, particularly emphasizing its environmental advantages. DEVELOPMENT STATUS also reports that early successes have been achieved by joint DOE/industry R D at The Geysers which will have important impacts on the future management of this mature field. Also there is increasing interest in hot dry rock. Analyses conducted in support of the NES indicate that if all the postulated technology developments occur in this field, the price of energy derived from hot dry rock in the US could drop.

  12. Decision-Making Accuracy of CBM Progress-Monitoring Data

    Science.gov (United States)

    Hintze, John M.; Wells, Craig S.; Marcotte, Amanda M.; Solomon, Benjamin G.

    2018-01-01

    This study examined the diagnostic accuracy associated with decision making as is typically conducted with curriculum-based measurement (CBM) approaches to progress monitoring. Using previously published estimates of the standard errors of estimate associated with CBM, 20,000 progress-monitoring data sets were simulated to model student reading…

  13. Metabonomics Research Progress on Liver Diseases.

    Science.gov (United States)

    Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

    2017-01-01

    Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

  14. Geothermal Progress Monitor report No. 5. Progress report, June 1981

    Energy Technology Data Exchange (ETDEWEB)

    1981-01-01

    Updated information is presented on activities and progress in the areas of electric power plants, direct heat applications, deep well drilling, leasing of federal lands, legislative and regulatory actions, research and development, and others. Special attention is given in this report to 1980 highlights, particularly in the areas of electric and direct heat uses, drilling, and the Federal lands leasing program. This report also includes a summary of the DOE FY 1982 geothermal budget request to Congress.

  15. Global disease monitoring and forecasting with Wikipedia.

    Science.gov (United States)

    Generous, Nicholas; Fairchild, Geoffrey; Deshpande, Alina; Del Valle, Sara Y; Priedhorsky, Reid

    2014-11-01

    Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: access logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with r2 up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.

  16. Global disease monitoring and forecasting with Wikipedia.

    Directory of Open Access Journals (Sweden)

    Nicholas Generous

    2014-11-01

    Full Text Available Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: access logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with r2 up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.

  17. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L

    2012-01-01

    The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North...

  18. Buccal Epithelial Cells as Potential Non- invasive Materials for the Monitoring of Mitochondrial Disturbances to Track Huntington‘s Disease Progression. A Pilot Study

    Czech Academy of Sciences Publication Activity Database

    Rodinová, M.; Trefilová, E.; Lišková, Irena; Klempíř, J.; Ellederová, Zdeňka; Vidinská, Daniela; Motlík, Jan; Zeman, J.; Hansíková, H.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 49-54 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. Liblice, 08.11.2015-10.11.2015] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington’s disease * mitochondrial respiratory chain complex I and IV * buccal epithelial cells Subject RIV: FH - Neurology Impact factor: 0.209, year: 2015

  19. Predictors of disease progression in HIV infection: a review

    Directory of Open Access Journals (Sweden)

    Ananworanich Jintanat

    2007-05-01

    Full Text Available Abstract During the extended clinically latent period associated with Human Immunodeficiency Virus (HIV infection the virus itself is far from latent. This phase of infection generally comes to an end with the development of symptomatic illness. Understanding the factors affecting disease progression can aid treatment commencement and therapeutic monitoring decisions. An example of this is the clear utility of CD4+ T-cell count and HIV-RNA for disease stage and progression assessment. Elements of the immune response such as the diversity of HIV-specific cytotoxic lymphocyte responses and cell-surface CD38 expression correlate significantly with the control of viral replication. However, the relationship between soluble markers of immune activation and disease progression remains inconclusive. In patients on treatment, sustained virological rebound to >10 000 copies/mL is associated with poor clinical outcome. However, the same is not true of transient elevations of HIV RNA (blips. Another virological factor, drug resistance, is becoming a growing problem around the globe and monitoring must play a part in the surveillance and control of the epidemic worldwide. The links between chemokine receptor tropism and rate of disease progression remain uncertain and the clinical utility of monitoring viral strain is yet to be determined. The large number of confounding factors has made investigation of the roles of race and viral subtype difficult, and further research is needed to elucidate their significance. Host factors such as age, HLA and CYP polymorphisms and psychosocial factors remain important, though often unalterable, predictors of disease progression. Although gender and mode of transmission have a lesser role in disease progression, they may impact other markers such as viral load. Finally, readily measurable markers of disease such as total lymphocyte count, haemoglobin, body mass index and delayed type hypersensitivity may come into favour

  20. Recent progress in online ultrasonic process monitoring

    Science.gov (United States)

    Wen, Szu-Sheng L.; Chen, Tzu-Fang; Ramos-Franca, Demartonne; Nguyen, Ky T.; Jen, Cheng-Kuei; Ihara, Ikuo; Derdouri, A.; Garcia-Rejon, Andres

    1998-03-01

    On-line ultrasonic monitoring of polymer co-extrusion and gas-assisted injection molding are presented. During the co- extrusion of high density polyethylene and Santoprene ultrasonic sensors consisting of piezoelectric transducers and clad ultrasonic buffer rods are used to detect the interface between these two polymers and the stability of the extrusion. The same ultrasonic sensor also measures the surface temperature of the extruded polymer. The results indicate that temperature measurements using ultrasound have a faster response time than those obtained by conventional thermocouple. In gas-assisted injection molding the polymer and gas flow front positions are monitored simultaneously. This information may be used to control the plunger movement.

  1. Ultrasonic Monitoring of the Progress of Lactic Acid Fermentation

    Science.gov (United States)

    Masuzawa, Nobuyoshi; Kimura, Akihiro; Ohdaira, Etsuzo

    2003-05-01

    Promotion of lactic acid fermentation by ultrasonic irradiation has been attempted. It is possible to determine the progress of fermentation and production of a curd, i.e., yoghurt and or kefir, by measuring acidity using a pH meter. However, this method is inconvenient and indirect for the evaluation of the progress of lactic acid fermentation under anaerobic condition. In this study, an ultrasonic monitoring method for evaluating the progress of lactic acid fermentation was examined.

  2. Allopurinol Against Progression of Chronic Kidney Disease.

    Science.gov (United States)

    Golmohammadi, Sima; Almasi, Afshin; Manouchehri, M; Omrani, Hamid Reza; Zandkarimi, Mohammad Reza

    2017-07-01

    Hyperuricemia is common in approximately 50% of patients with kidney failure due to decreased uric acid excretion, and it has been recently known as an independent factor in the progression of renal insufficiency. Allopurinol inhibits the production of uric acid. The aim of this study was to evaluate the effect of allopurinol on chronic kidney disease progression. In a clinical trial, patients with stages 3 and 4 of chronic kidney disease were divided into two groups to receive allopurinol, 100 mg, daily and placebo for 12 months. Patients' kidney function and serum uric acid levels were assessed at baseline and 3, 6, and 12 months after initial administration. Subgroups of patients with severe and mild glomerular filtration rate (GFR) impairment (GFR, 15 mL/min/1.73 m2 to 30 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to 60 mL/min/1.73 m2, respectively), were compared between the groups. Serum uric acid levels decreased significantly during after 12 months of allopurinol administration (P = .004). In patients with severe GFR impairment, serum creatinine levels did not decrease significantly and there was no significant increase in GFR, but in those with mild GFR impairment, serum creatinine levels decreased and GFR increase significantly (P kidney disease progression and could be administered with other effective medications for controlling the kidney disease.

  3. Progression of Late-Onset Stargardt Disease

    OpenAIRE

    Lambertus, Stanley; Lindner, Moritz; Bax, Nathalie M.; Mauschitz, Matthias M.; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; den Hollander, Anneke I.; Weber, Bernhard H. F.; Holz, Frank G.; van der Wilt, Gert Jan; Fleckenstein, Monika; Hoyng, Carel B.

    2016-01-01

    Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. Methods: We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype...

  4. Source Monitoring in Alzheimer's Disease

    Science.gov (United States)

    El Haj, Mohamad; Fasotti, Luciano; Allain, Philippe

    2012-01-01

    Source monitoring is the process of making judgments about the origin of memories. There are three categories of source monitoring: reality monitoring (discrimination between self- versus other-generated sources), external monitoring (discrimination between several external sources), and internal monitoring (discrimination between two types of…

  5. Teleosts Genomics: Progress and Prospects in Disease Prevention and Control

    Directory of Open Access Journals (Sweden)

    Hetron Mweemba Munang’andu

    2018-04-01

    Full Text Available Genome wide studies based on conventional molecular tools and upcoming omics technologies are beginning to gain functional applications in the control and prevention of diseases in teleosts fish. Herein, we provide insights into current progress and prospects in the use genomics studies for the control and prevention of fish diseases. Metagenomics has emerged to be an important tool used to identify emerging infectious diseases for the timely design of rational disease control strategies, determining microbial compositions in different aquatic environments used for fish farming and the use of host microbiota to monitor the health status of fish. Expounding the use of antimicrobial peptides (AMPs as therapeutic agents against different pathogens as well as elucidating their role in tissue regeneration is another vital aspect of genomics studies that had taken precedent in recent years. In vaccine development, prospects made include the identification of highly immunogenic proteins for use in recombinant vaccine designs as well as identifying gene signatures that correlate with protective immunity for use as benchmarks in optimizing vaccine efficacy. Progress in quantitative trait loci (QTL mapping is beginning to yield considerable success in identifying resistant traits against some of the highly infectious diseases that have previously ravaged the aquaculture industry. Altogether, the synopsis put forth shows that genomics studies are beginning to yield positive contribution in the prevention and control of fish diseases in aquaculture.

  6. Teleosts Genomics: Progress and Prospects in Disease Prevention and Control.

    Science.gov (United States)

    Munang'andu, Hetron Mweemba; Galindo-Villegas, Jorge; David, Lior

    2018-04-04

    Genome wide studies based on conventional molecular tools and upcoming omics technologies are beginning to gain functional applications in the control and prevention of diseases in teleosts fish. Herein, we provide insights into current progress and prospects in the use genomics studies for the control and prevention of fish diseases. Metagenomics has emerged to be an important tool used to identify emerging infectious diseases for the timely design of rational disease control strategies, determining microbial compositions in different aquatic environments used for fish farming and the use of host microbiota to monitor the health status of fish. Expounding the use of antimicrobial peptides (AMPs) as therapeutic agents against different pathogens as well as elucidating their role in tissue regeneration is another vital aspect of genomics studies that had taken precedent in recent years. In vaccine development, prospects made include the identification of highly immunogenic proteins for use in recombinant vaccine designs as well as identifying gene signatures that correlate with protective immunity for use as benchmarks in optimizing vaccine efficacy. Progress in quantitative trait loci (QTL) mapping is beginning to yield considerable success in identifying resistant traits against some of the highly infectious diseases that have previously ravaged the aquaculture industry. Altogether, the synopsis put forth shows that genomics studies are beginning to yield positive contribution in the prevention and control of fish diseases in aquaculture.

  7. Primary progressive aphasia: from syndrome to disease.

    Science.gov (United States)

    Matías-Guiu, J A; García-Ramos, R

    2013-01-01

    Primary progressive aphasia (PPA) is a clinical syndrome characterised by a progressive decline in language and speech of neurodegenerative origin. Major breakthroughs made in recent years have lent us a better understanding of this syndrome, which may be the first manifestation of any of a number of neurodegenerative diseases. We reviewed the main aspects of PPA epidemiology, clinical manifestations, diagnosis, aetiology and treatment. Most cases manifest sporadically and the typical age of onset is between 50 and 70 years. Three clinically distinct variants have been described: nonfluent or agrammatic PPA, semantic PPA and logopenic PPA. Each of these variants tends to be associated with specific histopathological findings, but clinical diagnostic methods are imperfect predictors of underlying pathology. Anatomical and functional neuroimaging can provide useful biomarkers. Several treatments have been proposed, and while no clear benefits have been demonstrated, acetylcholinesterase inhibitors may be useful, especially in the logopenic variant. PPA is an emerging syndrome which may be more prevalent than we might expect. It was previously listed as part of the frontotemporal dementia spectrum, and it is also related to Alzheimer disease. Clinical diagnosis, complemented by a biomarker evaluation, may predict the underlying pathology, which in turn will improve treatment possibilities. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  8. Serial Noninvasive Assessment of Apoptosis During Right Ventricular Disease Progression in Rats

    NARCIS (Netherlands)

    Campian, Maria E.; Verberne, Hein J.; Hardziyenka, Maxim; de Bruin, Kora; Selwaness, Mariana; van den Hoff, Maurice J. B.; Ruijter, Jan M.; van Eck-Smit, Berthe L. F.; de Bakker, Jacques M. T.; Tan, Hanno L.

    2009-01-01

    Right ventricular (RV) function is the major determinant of survival in patients with pulmonary hypertension. Yet, the pathophysiologic basis of RV disease is unresolved. We aimed to study the role of apoptosis in RV disease by monitoring it serially during disease progression using in vivo

  9. Mapping Neurodegenerative Disease Onset and Progression.

    Science.gov (United States)

    Seeley, William W

    2017-08-01

    Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining. Despite important advantages, postmortem studies cannot address in vivo, physiological, or longitudinal questions and have limited potential to explore early-stage disease except for the most common disorders. Emerging in vivo network-based neuroimaging strategies have begun to address these issues, providing data that complement the neuropathological tradition. Overall, findings to date highlight several fundamental principles of neurodegenerative disease anatomy and pathogenesis, as well as some enduring mysteries. These principles and mysteries provide a road map for future research. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  10. Clinical neurorestorative progress in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Chen L

    2015-06-01

    Full Text Available Lin Chen,1,2 Hongyun Huang,3–5 Wei-Ming Duan,6 Gengsheng Mao3 1Department of Neurosurgery, Yuquan Hospital, Tsinghua University, 2Department of Neurosurgery, Medical Center, Tsinghua University, 3Department of Neurosurgery, General Hospital of Chinese People's Armed Police Forces, 4Center of Cell Research, Beijing Rehabilitation Hospital of Capital Medical University, 5Beijing Hongtianji Neuroscience Academy, 6Department of Anatomy, Capital Medical University, Beijing, People's Republic of China Abstract: Parkinson’s disease (PD is one of the common neurodegenerative diseases. Besides the symptomatic therapies, the increasing numbers of neurorestorative therapies have shown the potential therapeutic value of reversing the neurodegenerative process and improving the patient's quality of life. Currrently available novel clinical neurorestorative strategies include pharmacological managements (glial cell-line derived neurotrophic factor, selegiline, recombinant human erythropoietin, neuromodulation intervention (deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, tissue and cell transplantation (fetal ventral mesencephalic tissue, sympathetic neurons, carotid body cells, bone marrow stromal cells, retinal pigment epithelium cells, gene therapy, and neurorehabilitative therapy. Herein, we briefly review the progress in this field and describe the neurorestorative mechanisms of the above-mentioned therapies for PD. Keywords: Parkinson’s disease, clinical study, neurorestorative treatment, cell transplantation, neuromodulation

  11. Gaucher disease: Progress and ongoing challenges.

    Science.gov (United States)

    Mistry, Pramod K; Lopez, Grisel; Schiffmann, Raphael; Barton, Norman W; Weinreb, Neal J; Sidransky, Ellen

    Over the past decades, tremendous progress has been made in the field of Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Many of the colossal achievements took place during the course of the sixty-year tenure of Dr. Roscoe Brady at the National Institutes of Health. These include the recognition of the enzymatic defect involved, the isolation and characterization of the protein, the localization and characterization of the gene and its nearby pseudogene, as well as the identification of the first mutant alleles in patients. The first treatment for Gaucher disease, enzyme replacement therapy, was conceived of, developed and tested at the Clinical Center of the National Institutes of Health. Advances including recombinant production of the enzyme, the development of mouse models, pioneering gene therapy experiments, high throughput screens of small molecules and the generation of induced pluripotent stem cell models have all helped to catapult research in Gaucher disease into the twenty-first century. The appreciation that mutations in the glucocerebrosidase gene are an important risk factor for parkinsonism further expands the impact of this work. However, major challenges still remain, some of which are described here, that will provide opportunities, excitement and discovery for the next generations of Gaucher investigators. Published by Elsevier Inc.

  12. Smart garments in chronic disease management: progress and challenges

    Science.gov (United States)

    Khosla, Ajit

    2012-10-01

    This paper presents the progress made developments in the area of Smart Garments for chronic disease management over last 10 years. A large number of health monitoring smart garments and wearable sensors have been manufactured to monitor patient's physiological parameters such as electrocardiogram, blood pressure, body temperature, heart rate, oxygen saturation, while patient is not in hospital. In last few years with the advancement in smartphones and cloud computing it is now possible to send the measure physiological data to any desired location. However there are many challenges in the development of smart garment systems. The two major challenges are development of new lightweight power sources and there is a need for global standardization and a road map for development of smart garments. In this paper we will discuss current state-of-theart smart garments and wearable sensor systems. Also discussed will be the new emerging trends in smart garment research and development.

  13. Epidemiological Concepts Regarding Disease Monitoring and Surveillance

    Directory of Open Access Journals (Sweden)

    Christensen Jette

    2001-03-01

    Full Text Available Definitions of epidemiological concepts regarding disease monitoring and surveillance can be found in textbooks on veterinary epidemiology. This paper gives a review of how the concepts: monitoring, surveillance, and disease control strategies are defined. Monitoring and surveillance systems (MO&SS involve measurements of disease occurrence, and the design of the monitoring determines which types of disease occurrence measures can be applied. However, the knowledge of the performance of diagnostic tests (sensitivity and specificity is essential to estimate the true occurrence of the disease. The terms, disease control programme (DCP or disease eradication programme (DEP, are defined, and the steps of DCP/DEP are described to illustrate that they are a process rather than a static MO&SS.

  14. Investigation progress of imaging techniques monitoring stem cell therapy

    International Nuclear Information System (INIS)

    Wu Jun; An Rui

    2006-01-01

    Recently stem cell therapy has showed potential clinical application in diabetes mellitus, cardiovascular diseases, malignant tumor and trauma. Efficient techniques of non-invasively monitoring stem cell transplants will accelerate the development of stem cell therapies. This paper briefly reviews the clinical practice of stem cell, in addition, makes a review of monitoring methods including magnetic resonance and radionuclide imaging which have been used in stem cell therapy. (authors)

  15. Natural History of Progression of Chronic Kidney Disease in Stages ...

    African Journals Online (AJOL)

    Natural History of Progression of Chronic Kidney Disease in Stages 4 and 5. ... Conclusion: Low serum bicarbonate level and high urinary protein excretion at baseline are independent predictors of progression in stage 4 and 5 CKD. Keywords: Chronic kidney disease; End stage renal disease; Glomerular filtration rate; ...

  16. [Various pathways leading to the progression of chronic liver diseases].

    Science.gov (United States)

    Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

    2016-02-21

    As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

  17. Connected speech as a marker of disease progression in autopsy-proven Alzheimer’s disease

    Science.gov (United States)

    Ahmed, Samrah; Haigh, Anne-Marie F.; de Jager, Celeste A.

    2013-01-01

    over the three stages of disease in syntactic complexity, semantic and lexical content. The findings suggest, first, that there is a progressive disruption in language integrity, detectable from the prodromal stage in a subset of patients with Alzheimer’s disease, and secondly that measures of semantic and lexical content and syntactic complexity best capture the global progression of linguistic impairment through the successive clinical stages of disease. The identification of disease-specific language impairment in prodromal Alzheimer’s disease could enhance clinicians’ ability to distinguish probable Alzheimer’s disease from changes attributable to ageing, while longitudinal assessment could provide a simple approach to disease monitoring in therapeutic trials. PMID:24142144

  18. Recent Progress in Biosensors for Environmental Monitoring: A Review.

    Science.gov (United States)

    Justino, Celine I L; Duarte, Armando C; Rocha-Santos, Teresa A P

    2017-12-15

    The environmental monitoring has been one of the priorities at the European and global scale due to the close relationship between the environmental pollution and the human health/socioeconomic development. In this field, the biosensors have been widely employed as cost-effective, fast, in situ, and real-time analytical techniques. The need of portable, rapid, and smart biosensing devices explains the recent development of biosensors with new transduction materials, obtained from nanotechnology, and for multiplexed pollutant detection, involving multidisciplinary experts. This review article provides an update on recent progress in biosensors for the monitoring of air, water, and soil pollutants in real conditions such as pesticides, potentially toxic elements, and small organic molecules including toxins and endocrine disrupting chemicals.

  19. Global Monitoring of the CTBT: Progress, Capabilities and Plans (Invited)

    Science.gov (United States)

    Zerbo, L.

    2013-12-01

    The Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO), established in 1996, is tasked with building up the verification regime of the CTBT. The regime includes a global system for monitoring the earth, the oceans and the atmosphere for nuclear tests, and an on-site inspection (OSI) capability. More than 80% of the 337 facilities of the International Monitoring System (IMS) have been installed and are sending data to the International Data Centre (IDC) in Vienna, Austria for processing. These IMS data along with IDC processed and reviewed products are available to all States that have signed the Treaty. Concurrent with the build-up of the global monitoring networks, near-field geophysical methods are being developed and tested for OSIs. The monitoring system is currently operating in a provisional mode, as the Treaty has not yet entered into force. Progress in installing and operating the IMS and the IDC and in building up an OSI capability will be described. The capabilities of the monitoring networks have progressively improved as stations are added to the IMS and IDC processing techniques refined. Detection thresholds for seismic, hydroacoustic, infrasound and radionuclide events have been measured and in general are equal to or lower than the predictions used during the Treaty negotiations. The measurements have led to improved models and tools that allow more accurate predictions of future capabilities and network performance under any configuration. Unplanned tests of the monitoring network occurred when the DPRK announced nuclear tests in 2006, 2009, and 2013. All three tests were well above the detection threshold and easily detected and located by the seismic monitoring network. In addition, noble gas consistent with the nuclear tests in 2006 and 2013 (according to atmospheric transport models) was detected by stations in the network. On-site inspections of these tests were not conducted as the Treaty has not entered

  20. Effect of disease stage on progression of hydroxychloroquine retinopathy.

    Science.gov (United States)

    Marmor, Michael F; Hu, Julia

    2014-09-01

    Hydroxychloroquine sulfate retinopathy can progress after the drug is stopped. It is not clear how this relates to the stage of retinopathy or whether early screening with modern imaging technology can prevent progression and visual loss. To determine the relationship between progression of retinopathy and the severity of disease using objective data from optical coherence tomography and assess the value of early screening for the toxic effects of hydroxychloroquine. Clinical findings in patients with hydroxychloroquine retinopathy were monitored with repeated anatomical and functional examinations for 13 to 40 months after the drug was stopped in a referral practice in a university medical center. Eleven patients participated, with the severity of toxic effects categorized as early (patchy parafoveal damage shown on field or objective testing), moderate (a 50%-100% parafoveal ring of optical coherence tomography thinning but intact retinal pigment epithelium), and severe (visible bull's-eye damage). Visual acuity, white 10-2 visual field pattern density plots, fundus autofluorescence, spectral-density optical coherence tomography cross sections, thickness (from cube diagrams), and ellipsoid zone length. Visual acuity and visual fields showed no consistent change. Fundus autofluorescence showed little or no change except in severe cases in which the bull's-eye damage expanded progressively. Optical coherence tomography cross sections showed little visible change in early and moderate cases but progressive foveal thinning (approximately 7 μm/y) and loss of ellipsoid zone (in the range of 100 μm/y) in severe cases, which was confirmed by quantitative measurements. The measurements also showed some foveal thinning (approximately 4 μm/y) and deepening of parafoveal loss in moderate cases, but the breadth of the ellipsoid zone remained constant in both early and moderate cases. A few cases showed a suggestion of ellipsoid zone improvement. Patients with

  1. When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

    Science.gov (United States)

    2012-01-01

    Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

  2. Use of the Progressive Aphasia Severity Scale (PASS) in monitoring speech and language status in PPA

    Science.gov (United States)

    Sapolsky, Daisy; Domoto-Reilly, Kimiko; Dickerson, Bradford C.

    2014-01-01

    Background Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome involving the gradual development of aphasia, slowly impairing the patient’s ability to communicate. Pharmaceutical treatments do not currently exist and intervention often focuses on speech-language behavioral therapies, although further investigation is warranted to determine how best to harness functional benefits. Efforts to develop pharmaceutical and behavioral treatments have been hindered by a lack of standardized methods to monitor disease progression and treatment efficacy. Aims Here we describe our current approach to monitoring progression of PPA, including the development and applications of a novel clinical instrument for this purpose, the Progressive Aphasia Severity Scale (PASS). We also outline some of the issues related to initial evaluation and longitudinal monitoring of PPA. Methods & Procedures In our clinical and research practice we perform initial and follow-up assessments of PPA patients using a multi-faceted approach. In addition to standardized assessment measures, we use the PASS to rate presence and severity of symptoms across distinct domains of speech, language, and functional and pragmatic aspects of communication. Ratings are made using the clinician’s best judgment, integrating information from patient test performance in the office as well as a companion’s description of routine daily functioning. Outcomes & Results Monitoring symptom characteristics and severity with the PASS can assist in developing behavioral therapies, planning treatment goals, and counseling patients and families on clinical status and prognosis. The PASS also has potential to advance the implementation of PPA clinical trials. Conclusions PPA patients display heterogeneous language profiles that change over time given the progressive nature of the disease. The monitoring of symptom progression is therefore crucial to ensure that proposed treatments are appropriate at

  3. Identification of genetic variants associated with Huntington's disease progression

    DEFF Research Database (Denmark)

    Hensman Moss, Davina J; Pardiñas, Antonio F; Langbehn, Douglas

    2017-01-01

    indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers...... in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression......BACKGROUND: Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate...

  4. Using expectations to monitor robotic progress and recover from problems

    Science.gov (United States)

    Kurup, Unmesh; Lebiere, Christian; Stentz, Anthony; Hebert, Martial

    2013-05-01

    How does a robot know when something goes wrong? Our research answers this question by leveraging expectations - predictions about the immediate future - and using the mismatch between the expectations and the external world to monitor the robot's progress. We use the cognitive architecture ACT-R (Adaptive Control of Thought - Rational) to learn the associations between the current state of the robot and the world, the action to be performed in the world, and the future state of the world. These associations are used to generate expectations that are then matched by the architecture with the next state of the world. A significant mismatch between these expectations and the actual state of the world indicate a problem possibly resulting from unexpected consequences of the robot's actions, unforeseen changes in the environment or unanticipated actions of other agents. When a problem is detected, the recovery model can suggest a number of recovery options. If the situation is unknown, that is, the mismatch between expectations and the world is novel, the robot can use a recovery solution from a set of heuristic options. When a recovery option is successfully applied, the robot learns to associate that recovery option with the mismatch. When the same problem is encountered later, the robot can apply the learned recovery solution rather than using the heuristics or randomly exploring the space of recovery solutions. We present results from execution monitoring and recovery performed during an assessment conducted at the Combined Arms Collective Training Facility (CACTF) at Fort Indiantown Gap.

  5. Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Lildballe, Dorte Launholt; Nguyen, Khoa Tran; Poulsen, Steen Seier

    2011-01-01

    No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker.......No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker....

  6. Progression of Late-Onset Stargardt Disease

    NARCIS (Netherlands)

    Lambertus, S.; Lindner, M.; Bax, N.M.; Mauschitz, M.M.; Nadal, J.; Schmid, M.; Schmitz-Valckenberg, S.; Hollander, A.I. den; Weber, B.H.; Holz, F.G.; Wilt, G.J. van der; Fleckenstein, M.; Hoyng, C.B.

    2016-01-01

    Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy

  7. Clinical course of nonalcoholic fatty liver disease: an assessment of severity, progression, and outcomes

    Directory of Open Access Journals (Sweden)

    Simeone JC

    2017-12-01

    disease progression, and mortality risk increased with disease stage. Early diagnosis and monitoring of disease progression, especially in patients with T2DM, is warranted. Keywords: NAFLD, clinical course, disease progression, multistate model, retrospective study, type 2 diabetes

  8. Reduced serum myostatin concentrations associated with genetic muscle disease progression.

    Science.gov (United States)

    Burch, Peter M; Pogoryelova, Oksana; Palandra, Joe; Goldstein, Richard; Bennett, Donald; Fitz, Lori; Guglieri, Michela; Bettolo, Chiara Marini; Straub, Volker; Evangelista, Teresinha; Neubert, Hendrik; Lochmüller, Hanns; Morris, Carl

    2017-03-01

    Myostatin is a highly conserved protein secreted primarily from skeletal muscle that can potently suppress muscle growth. This ability to regulate skeletal muscle mass has sparked intense interest in the development of anti-myostatin therapies for a wide array of muscle disorders including sarcopenia, cachexia and genetic neuromuscular diseases. While a number of studies have examined the circulating myostatin concentrations in healthy and sarcopenic populations, very little data are available from inherited muscle disease patients. Here, we have measured the myostatin concentration in serum from seven genetic neuromuscular disorder patient populations using immunoaffinity LC-MS/MS. Average serum concentrations of myostatin in all seven muscle disease patient groups were significantly less than those measured in healthy controls. Furthermore, circulating myostatin concentrations correlated with clinical measures of disease progression for five of the muscle disease patient populations. These findings greatly expand the understanding of myostatin in neuromuscular disease and suggest its potential utility as a biomarker of disease progression.

  9. Monitoring the progress of non-enzymatic glycation in vitro

    International Nuclear Information System (INIS)

    Shaw, S.M.; Crabbe, M.J.

    1994-01-01

    The progress of in vitro non-enzymatic glycation of bovine serum albumin was followed by using 14 C-glucose and a nitroblue tetrazolium assay, absorption and fluorescence spectroscopy, SDS gel electrophoresis and protease digestion. The number of adducts detectable using both 14 C-tracers and a fructosamine assay remained low at physiological glucose concentrations, fewer than five adducts being detectable. When glucose concentrations > 1.0 M were used the number of adducts was found to greatly exceed the number of lysyl residues available in BSA, indicative of cross-linking between Maillard products. Incubation of BSA with glucose concentrations of up to 160 mM for one month produced no observable increase in molecular weight by SDS gel electrophoresis, showing that at physiological glucose concentrations, increases in molecular weight were minimal for short incubation periods. Increases in absorption were proportial to both the glucose concentration and the incubation time. Several absorption peaks, at 370, 488 and 554 nm, were consistent in appearance throughout the course of each incubation. Fluorescence spectroscopy of the modified proteins showed a disappearance of the fluorescence associated with peptide bonds and aromatic residues and the appearance of a broad peak at longer wavelengths due to the wide range of absorptive/fluorescent wavelengths of the developing Maillard products. Protease digestion gave similar patterns with non-glycated and glycated protein, suggesting that glycation did not block digestion sites, and that partial digestion did not cause significant further exposure of susceptible sites. Our results show that while glycation ultimately results in protein conformational changes and the formation of large molecular weight species, these occur at a relatively late stage in the maturation of protein Maillard products, after ≥ nine months of incubation with glucose concentration of ≥ 20 mM. Monitoring of AGE maturation in vitro is better

  10. Glutathione dysregulation and the etiology and progression of human diseases.

    NARCIS (Netherlands)

    Ballatori, N.; Krance, S.M.; Notenboom, S.; Shi, S.; Tieu, K.; Hammond, C.L.

    2009-01-01

    Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases

  11. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    International Nuclear Information System (INIS)

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

  12. Central Blood Pressure and Chronic Kidney Disease Progression

    Directory of Open Access Journals (Sweden)

    Debbie L. Cohen

    2011-01-01

    Full Text Available Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.

  13. Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9).

    Science.gov (United States)

    Strauss, Rupert W; Muñoz, Beatriz; Ho, Alexander; Jha, Anamika; Michaelides, Michel; Cideciyan, Artur V; Audo, Isabelle; Birch, David G; Hariri, Amir H; Nittala, Muneeswar G; Sadda, SriniVas; West, Sheila; Scholl, Hendrik P N

    2017-11-01

    progression depended on the initial size of the lesion. In Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.

  14. Does monitoring goal progress promote goal attainment? A meta-analysis of the experimental evidence.

    Science.gov (United States)

    Harkin, Benjamin; Webb, Thomas L; Chang, Betty P I; Prestwich, Andrew; Conner, Mark; Kellar, Ian; Benn, Yael; Sheeran, Paschal

    2016-02-01

    Control theory and other frameworks for understanding self-regulation suggest that monitoring goal progress is a crucial process that intervenes between setting and attaining a goal, and helps to ensure that goals are translated into action. However, the impact of progress monitoring interventions on rates of behavioral performance and goal attainment has yet to be quantified. A systematic literature search identified 138 studies (N = 19,951) that randomly allocated participants to an intervention designed to promote monitoring of goal progress versus a control condition. All studies reported the effects of the treatment on (a) the frequency of progress monitoring and (b) subsequent goal attainment. A random effects model revealed that, on average, interventions were successful at increasing the frequency of monitoring goal progress (d+ = 1.98, 95% CI [1.71, 2.24]) and promoted goal attainment (d+ = 0.40, 95% CI [0.32, 0.48]). Furthermore, changes in the frequency of progress monitoring mediated the effect of the interventions on goal attainment. Moderation tests revealed that progress monitoring had larger effects on goal attainment when the outcomes were reported or made public, and when the information was physically recorded. Taken together, the findings suggest that monitoring goal progress is an effective self-regulation strategy, and that interventions that increase the frequency of progress monitoring are likely to promote behavior change. (c) 2016 APA, all rights reserved).

  15. Natural Besnoitia besnoiti infections in cattle: chronology of disease progression.

    Science.gov (United States)

    Gollnick, Nicole S; Scharr, Julia C; Schares, Gereon; Langenmayer, Martin C

    2015-02-14

    Bovine besnoitiosis is an emerging protozoan disease in cattle. Neither vaccines nor chemotherapeutic drugs are currently available for prevention and treatment of Besnoitia besnoiti infections. Therefore the implementation of appropriate disease management strategies is of utmost importance. The aim of this longitudinal study was to complement current knowledge on the chronology of disease progression. This was realized by correlating clinical findings in early stages of naturally acquired bovine besnoitiosis with results of real-time PCR of skin biopsies and of two western immunoblots and an immunofluorescent antibody test (IFAT). Animals for this study were obtained by i) closely monitoring a cow-calf operation with a high prevalence of bovine besnoitiosis for cases of acute disease, and by ii) conducting a 12-week cohabitation experiment on pasture with five healthy heifers, a healthy bull and five B. besnoiti infected cows. A control group of six healthy heifers was kept at a minimal distance of 20 m. Further, the spectrum of potential insect vectors was determined. Infected cattle were followed up to a maximum of 221 days after first detection of B. besnoiti antibodies. Two severely affected cows developed visible and palpable alterations of skin, a decrease in body condition despite good feed intake, and chronic bovine besnoitiosis-associated laminitis leading to non-healing sole ulcers. The cows also had high reciprocal IFAT titers and high loads of parasite DNA in skin samples. Two heifers developed a mild clinical course characterized by few parasitic cysts visible in the scleral conjunctivae and vestibula vaginae. Both heifers became infected during the time of high insect activity of the species Musca domestica, Musca autumnalis, Haematobia irritans, and Stomoxys calcitrans. When a third heifer became subclinically infected, low insect activity was recorded. None of the six control heifers contracted a B. besnoiti infection. In chronic besnoitiosis

  16. Therapeutic Drug Monitoring in Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    NG Hoi-Yan Alexandra

    2016-12-01

    Full Text Available The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors.

  17. Gas bubble disease monitoring and research of juvenile salmonids

    International Nuclear Information System (INIS)

    Maule, A.G.; Beeman, J.; Hans, K.M.; Mesa, M.G.; Haner, P.; Warren, J.J.

    1997-10-01

    This document describes the project activities 1996--1997 contract year. This report is composed of three chapters which contain data and analyses of the three main elements of the project: field research to determine the vertical distribution of migrating juvenile salmonids, monitoring of juvenile migrants at dams on the Snake and Columbia rivers, and laboratory experiments to describe the progression of gas bubble disease signs leading to mortality. The major findings described in this report are: A miniature pressure-sensitive radio transmitter was found to be accurate and precise and, after compensation for water temperature, can be used to determine the depth of tagged-fish to within 0.32 m of the true depth (Chapter 1). Preliminary data from very few fish suggest that depth protects migrating juvenile steelhead from total dissolved gas supersaturation (Chapter 1). As in 1995, few fish had any signs of gas bubble disease, but it appeared that prevalence and severity increased as fish migrated downstream and in response to changing gas supersaturation (Chapter 2). It appeared to gas bubble disease was not a threat to migrating juvenile salmonids when total dissolved gas supersaturation was < 120% (Chapter 2). Laboratory studies suggest that external examinations are appropriate for determining the severity of gas bubble disease in juvenile salmonids (Chapter 3). The authors developed a new method for examining gill arches for intravascular bubbles by clamping the ventral aorta to reduce bleeding when arches were removed (Chapter 3). Despite an outbreak of bacterial kidney disease in the experimental fish, the data indicate that gas bubble disease is a progressive trauma that can be monitored (Chapter 3)

  18. Periodontal profile classes predict periodontal disease progression and tooth loss.

    Science.gov (United States)

    Morelli, Thiago; Moss, Kevin L; Preisser, John S; Beck, James D; Divaris, Kimon; Wu, Di; Offenbacher, Steven

    2018-02-01

    Current periodontal disease taxonomies have limited utility for predicting disease progression and tooth loss; in fact, tooth loss itself can undermine precise person-level periodontal disease classifications. To overcome this limitation, the current group recently introduced a novel patient stratification system using latent class analyses of clinical parameters, including patterns of missing teeth. This investigation sought to determine the clinical utility of the Periodontal Profile Classes and Tooth Profile Classes (PPC/TPC) taxonomy for risk assessment, specifically for predicting periodontal disease progression and incident tooth loss. The analytic sample comprised 4,682 adult participants of two prospective cohort studies (Dental Atherosclerosis Risk in Communities Study and Piedmont Dental Study) with information on periodontal disease progression and incident tooth loss. The PPC/TPC taxonomy includes seven distinct PPCs (person-level disease pattern and severity) and seven TPCs (tooth-level disease). Logistic regression modeling was used to estimate relative risks (RR) and 95% confidence intervals (CI) for the association of these latent classes with disease progression and incident tooth loss, adjusting for examination center, race, sex, age, diabetes, and smoking. To obtain personalized outcome propensities, risk estimates associated with each participant's PPC and TPC were combined into person-level composite risk scores (Index of Periodontal Risk [IPR]). Individuals in two PPCs (PPC-G: Severe Disease and PPC-D: Tooth Loss) had the highest tooth loss risk (RR = 3.6; 95% CI = 2.6 to 5.0 and RR = 3.8; 95% CI = 2.9 to 5.1, respectively). PPC-G also had the highest risk for periodontitis progression (RR = 5.7; 95% CI = 2.2 to 14.7). Personalized IPR scores were positively associated with both periodontitis progression and tooth loss. These findings, upon additional validation, suggest that the periodontal/tooth profile classes and the derived

  19. Lipid-Altering Therapies and the Progression of Atherosclerotic Disease

    International Nuclear Information System (INIS)

    Wierzbicki, Anthony S.

    2007-01-01

    Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents, including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focused and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease

  20. Progressive neuronal degeneration of childhood with liver disease

    International Nuclear Information System (INIS)

    Kendall, B.E.; Boyd, S.G.; Egger, J.; Harding, B.N.

    1987-01-01

    The clinical, electrophysiological and neuroradiological features of thirteen patients suffering from progressive neuronal degeneration of childhood with liver failure are presented. The disease commonly presents very early in life with progressive mental retardation, followed by intractable epilepsy, and should be suspected clinically especially if there is a family history of similar disorder in a sibling. On computed tomography there are low density regions, particularly in the occipital and posterior temporal lobes, involving both cortex and white matter, combined with or followed by progressive atrophy. Typical EEG findings may be confirmatory. (orig.)

  1. Monitoring Progress in Child Poverty Reduction: Methodological Insights and Illustration to the Case Study of Bangladesh

    Science.gov (United States)

    Roche, Jose Manuel

    2013-01-01

    Important steps have been taken at international summits to set up goals and targets to improve the wellbeing of children worldwide. Now the world also has more and better data to monitor progress. This paper presents a new approach to monitoring progress in child poverty reduction based on the Alkire and Foster adjusted headcount ratio and an…

  2. Behavioral-Progress Monitoring Using the Electronic Daily Behavioral Report Card (e-DBRC) System

    Science.gov (United States)

    Burke, Mack D.; Vannest, Kimberly J.

    2008-01-01

    In this article, the authors present an overview of a Web-based electronic system for behavioral-progress monitoring. Behavioral-progress monitoring is necessary to evaluate responsiveness to behavioral interventions, the effects of positive behavioral support, and the attainment of individualized education program goals and objectives. The…

  3. State of progress in treating cystic fibrosis respiratory disease

    Directory of Open Access Journals (Sweden)

    Flume Patrick A

    2012-08-01

    Full Text Available Abstract Since the discovery of the gene associated with cystic fibrosis (CF, there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.

  4. Quantification of disease progression of several microbial pathogens on Arabidopsis thaliana using real-time fluorescence PCR

    NARCIS (Netherlands)

    Brouwer, M.; Lievens, B.; Hemelrijck, van W.; Ackerveken, van den G.; Cammue, B.P.A.; Thomma, B.P.H.J.

    2003-01-01

    An accurate monitoring of disease progression is important to evaluate disease susceptibility phenotypes. Over the years, Arabidopsis thaliana has become the model species to serve as a host in plant-pathogen interactions. Despite the efforts to study genetic mechanisms of host defense, little

  5. Epidemiological monitoring for emerging infectious diseases

    Science.gov (United States)

    Greene, Marjorie

    2010-04-01

    The Homeland Security News Wire has been reporting on new ways to fight epidemics using digital tools such as iPhone, social networks, Wikipedia, and other Internet sites. Instant two-way communication now gives consumers the ability to complement official reports on emerging infectious diseases from health authorities. However, there is increasing concern that these communications networks could open the door to mass panic from unreliable or false reports. There is thus an urgent need to ensure that epidemiological monitoring for emerging infectious diseases gives health authorities the capability to identify, analyze, and report disease outbreaks in as timely and efficient a manner as possible. One of the dilemmas in the global dissemination of information on infectious diseases is the possibility that information overload will create inefficiencies as the volume of Internet-based surveillance information increases. What is needed is a filtering mechanism that will retrieve relevant information for further analysis by epidemiologists, laboratories, and other health organizations so they are not overwhelmed with irrelevant information and will be able to respond quickly. This paper introduces a self-organizing ontology that could be used as a filtering mechanism to increase relevance and allow rapid analysis of disease outbreaks as they evolve in real time.

  6. Disruption of gut homeostasis by opioids accelerates HIV disease progression

    Directory of Open Access Journals (Sweden)

    Jingjing eMeng

    2015-06-01

    Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

  7. Sodium intake, RAAS-blockade and progressive renal disease

    NARCIS (Netherlands)

    de Borst, Martin H; Navis, Gerjan

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the

  8. Slow progression of paediatric HIV disease: Selective adaptation or ...

    African Journals Online (AJOL)

    In the European Caucasian populations, the chemokine-cell receptor variant CCR5 \\"Delta 32\\" is a the genetic determinant of HIV disease progression that is believed to have been selected for in the general population by exposure to antigens closely interlinked to HIV like Yersinia pestis or small pox virus. Among African ...

  9. A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial

    Science.gov (United States)

    2014-01-01

    186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance. Discussion This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression. Trial registration This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008). PMID:24997587

  10. Recent progress in ERCP for biliary and pancreatic diseases

    Directory of Open Access Journals (Sweden)

    MIAO Lin

    2014-12-01

    Full Text Available In recent years, with the continuous development of endoscopic and interventional techniques, many new devices and methods have been used in clinical practice, and the application of endoscopic retrograde cholangiopancreatography (ERCP in biliary and pancreatic diseases has developed rapidly. This paper reviews and summarizes the recent progress in ERCP among patients with biliary and pancreatic diseases, including those with altered gastrointestinal anatomy, pregnant patients, patients with benign and malignant biliary strictures, and patients with pancreatic pseudocysts, as well as the application of SpyGlass, photodynamic therapy, and radiofrequency ablation, the management of ERCP-related duodenal perforation, and the prevention of post-ERCP pancreatitis. All the progress has made a great contribution to the diagnosis and treatment of biliary and pancreatic diseases.

  11. Geothermal Progress Monitor Report No. 2, January/February 1980

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-01

    Progress is reviewed in the following aspects of the program: electrical uses; direct-heat uses; leases; outreach and technical assistance; general activities; legal, institutional, and regulatory activities; and reports and publications. (MHR)

  12. Caffeine, creatine, GRIN2A and Parkinson's disease progression.

    Science.gov (United States)

    Simon, David K; Wu, Cai; Tilley, Barbara C; Lohmann, Katja; Klein, Christine; Payami, Haydeh; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Dewey, Richard; Hauser, Robert A; Schaake, Susen; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wei, Peng; Wong, Pei Shieen; Yang, Tianzhong

    2017-04-15

    Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Progress and lessons learned from water-quality monitoring networks

    Science.gov (United States)

    Myers, Donna N.; Ludtke, Amy S.

    2017-01-01

    Stream-quality monitoring networks in the United States were initiated and expanded after passage of successive federal water-pollution control laws from 1948 to 1972. The first networks addressed information gaps on the extent and severity of stream pollution and served as early warning systems for spills. From 1965 to 1972, monitoring networks expanded to evaluate compliance with stream standards, track emerging issues, and assess water-quality status and trends. After 1972, concerns arose regarding the ability of monitoring networks to determine if water quality was getting better or worse and why. As a result, monitoring networks adopted a hydrologic systems approach targeted to key water-quality issues, accounted for human and natural factors affecting water quality, innovated new statistical methods, and introduced geographic information systems and models that predict water quality at unmeasured locations. Despite improvements, national-scale monitoring networks have declined over time. Only about 1%, or 217, of more than 36,000 US Geological Survey monitoring sites sampled from 1975 to 2014 have been operated throughout the four decades since passage of the 1972 Clean Water Act. Efforts to sustain monitoring networks are important because these networks have collected information crucial to the description of water-quality trends over time and are providing information against which to evaluate future trends.

  14. [Hepatobiliary System Diseases as the Predictors of Psoriasis Progression].

    Science.gov (United States)

    Smirnova, S V; Barilo, A A; Smolnikova, M V

    2016-01-01

    To assess the state of the hepatobiliary system in psoriasis andpsoriatic arthritis in order to establish a causal relationship and to identify clinical and functional predictors of psoriatic disease progression. The study includedpatients with extensive psoriasis vulgaris (n = 175) aged 18 to 66 years old and healthy donors (n = 30), matched by sex and age: Group 1--patients with psoriasis (PS, n = 77), group 2--patients with psoriatic arthritis (PsA, n = 98), group 3--control. The evaluation of functional state of the hepatobiliary system was performed by the analysis of the clinical and anamnestic data and by the laboratory-instrumental methods. We identified predictors of psoriasis: triggers (stress and nutritionalfactor), increased total bilirubin, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, eosinophilia, giardiasis, carriers of hepatitis C virus, ductal changes andfocal leisons in the liver, thickening of the walls of the gallbladder detected by ultrasound. Predictors ofpsoriatic arthritis: age over 50 years, dyspeptic complaints, the presence of hepatobiliary system diseases, the positive right hypochondrium syndrome, the clinical symptoms of chronic cholecystitis, excess body weight, high levels of bilirubin, cholesterol and low density lipoprotein, hepatomegaly, non-alcoholic fatty liver disease. High activity of hepatocytes cytolysis, cholestasis, inflammation, metabolic disorders let us considerpsoriatic arthritis as a severe clinical stage psoriatic disease when the hepatobiliary system, in turn, is one of the main target organs in systemic psoriatic process. Non-alcoholic fatty liver disease and chronic cholecystitis are predictors of psoriatic disease progression.

  15. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis?

    DEFF Research Database (Denmark)

    Dalgas, Ulrik; Stenager, Egon

    2012-01-01

    studies evaluating the effects on clinical outcome measures, (2) cross-sectional studies evaluating the relationship between fitness status and MRI findings, (3) cross-sectional and longitudinal studies evaluating the relationship between exercise/physical activity and disability/relapse rate and, finally......, (4) longitudinal exercise studies applying the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Data from intervention studies evaluating disease progression by clinical measures (1) do not support a disease-modifying effect of exercise; however, MRI data (2), patient-reported data...... (3) and data from the EAE model (4) indicate a possible disease-modifying effect of exercise, but the strength of the evidence limits definite conclusions. It was concluded that some evidence supports the possibility of a disease-modifying potential of exercise (or physical activity) in MS patients...

  16. Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

    DEFF Research Database (Denmark)

    Haynes, Richard; Lewis, David; Emberson, Jonathan

    2014-01-01

    Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily...... or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared...... with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD....

  17. Progression of disease preceding lower extremity amputation in Denmark

    DEFF Research Database (Denmark)

    Jensen, Pia Søe; Petersen, Janne; Kirketerp-Møller, Klaus

    2017-01-01

    OBJECTIVES: Patients with non-traumatic lower extremity amputation are characterised by high age, multi-morbidity and polypharmacy and long-term complications of atherosclerosis and diabetes. To ensure early identification of patients at risk of amputation, we need to gain knowledge about...... the progression of diseases related to lower extremity amputations during the years preceding the amputation. DESIGN: A retrospective population-based national registry study. SETTING: The study includes data on demographics, diagnoses, surgery, medications and healthcare services from five national registries....... Data were retrieved from 14 years before until 1 year after the amputation. Descriptive statistics were used to describe the progression of diseases and use of medication and healthcare services. PARTICIPANTS: An unselected cohort of patients (≥50 years; n=2883) subjected to a primary non...

  18. Marine litter monitoring by northern fulmars: progress report 2002

    NARCIS (Netherlands)

    Franeker, van J.A.; Meijboom, A.

    2003-01-01

    An earlier pilot study on litter contents in stomachs of Fulmars indicated that this seabird can be used as a suitable indicator for levels of marine litter pollution on the North Sea off the Dutch coast. This progress report updates the existing dataset with data on Fulmar stomach contents in the

  19. Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3

    International Nuclear Information System (INIS)

    Ulm, Franz-Josef

    2000-01-01

    OAK-B135 Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3(NOTE: Part II A item 1 indicates ''PAPER'', but a report is attached electronically)

  20. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    Science.gov (United States)

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  1. FY09 PROGRESS: MULTI-ISOTOPE PROCESS (MIP) MONITOR

    International Nuclear Information System (INIS)

    Schwantes, Jon M.; Orton, Christopher R.; Fraga, Carlos G.; Christensen, Richard; Laspe, Amy R.; Ward, Rebecca M.

    2009-01-01

    Model and experimental estimates of the Multi-Isotope Process Monitor performance for determining burnup after dissolution and acid concentration during solvent extraction steps during reprocessing of spent nuclear fuel are presented. Modern industrial reprocessing techniques, including the PUREX and UREX+ family of separations technologies, are based on solvent extraction between organic and aqueous phases. In these bi-phase systems, product (actinide) and contaminant (fission and activation products) elements are preferentially driven (thermodynamically) to opposite phases, with small amounts of each remaining in the other phase. The distribution of each element, between the organic and aqueous phases, is determined by major process variables such as acid concentration, organic ligand concentration, reduction potential, and temperature. Hence, for consistent performance of the separation process, the distribution of each element between the organic and aqueous phases should be relatively constant. During 'normal' operations the pattern of elements distributing into the product and waste streams at each segment of the facility should be reproducible, resulting in a statistically significant signature of the nominal process conditions. Under 'abnormal' conditions, such as those expected under some protracted diversion scenarios, patterns of elements within the various streams would be expected to change measurably. The MIP monitoring approach utilizes changes in the concentrations of gamma-emitting elements as evidence of changes to the process chemistry. It exploits a suite of gamma emitting isotopes to track multiple chemical species and behaviors simultaneously, thus encompassing a large array of elements that are affected by chemical and physical changes. In-process surveillance by the MIP monitor is accomplished by coupling the gamma spectrometry of the streams with multivariate techniques, such as Principal Component Analysis (PCA). PCA is a chemometrics tool

  2. Urinary endotrophin predicts disease progression in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Rasmussen, Daniel Guldager Kring; Fenton, Anthony; Jesky, Mark

    2017-01-01

    Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate...... information regarding CKD progression may improve clinical decisions. We tested the hypothesis that urinary endotrophin derived during COL VI deposition in fibrotic human kidneys is a marker for progression of CKD in the Renal Impairment in Secondary Care (RIISC) cohort, a prospective observational study...... of 499 CKD patients. Endotrophin localised to areas of increased COL VI deposition in fibrotic kidneys but was not present in histologically normal kidneys. The third and fourth quartiles of urinary endotrophin:creatinine ratio (ECR) were independently associated with one-year disease progression after...

  3. [Application of lysosomal detection in marine pollution monitoring: research progress].

    Science.gov (United States)

    Weng, You-Zhu; Fang, Yong-Qiang; Zhang, Yu-Sheng

    2013-11-01

    Lysosome is an important organelle existing in eukaryotic cells. With the development of the study on the structure and function of lysosome in recent years, lysosome is considered as a target of toxic substances on subcellular level, and has been widely applied abroad in marine pollution monitoring. This paper summarized the biological characteristics of lysosomal marker enzyme, lysosome-autophagy system, and lysosomal membrane, and introduced the principles and methods of applying lysosomal detection in marine pollution monitoring. Bivalve shellfish digestive gland and fish liver are the most sensitive organs for lysosomal detection. By adopting the lysosomal detection techniques such as lysosomal membrane stability (LMS) test, neutral red retention time (NRRT) assay, morphological measurement (MM) of lysosome, immunohistochemical (Ih) assay of lysosomal marker enzyme, and electron microscopy (EM), the status of marine pollution can be evaluated. It was suggested that the lysosome could be used as a biomarker for monitoring marine environmental pollution. The advantages and disadvantages of lysosomal detection and some problems worthy of attention were analyzed, and the application prospects of lysosomal detection were discussed.

  4. Antioxidant effect of Morus nigra on Chagas disease progression.

    Science.gov (United States)

    Montenote, Michelly Cristina; Wajsman, Vithor Zuccaro; Konno, Yoichi Takaki; Ferreira, Paulo César; Silva, Regildo Márcio Gonçalves; Therezo, Altino Luiz Silva; Silva, Luciana Pereira; Martins, Luciamáre Perinetti Alves

    2017-11-06

    Considering the widespread popular use of Morus nigra and the amount of scientific information on its antioxidant and anti-inflammatory activity, the effectiveness of this phytotherapeutic compound in the parasitemia progression during the acute phase of Chagas disease and its role in the development of the inflammatory process as well as its effects on the oxidative damage in the chronic phase of infection were evaluated. Thus, 96 male Swiss mice were randomly divided into eight groups, four groups were uninfected controls, and four groups were intraperitoneally infected with 5.0 x 104 blood trypomastigotes forms of T. cruzi QM2 strain. Four batches composed of one uninfected and one infected group were respectively treated with 70% alcohol solution and 25 μL, 50 μL and 75 μL of the phytotherapeutic compound. Levels of antioxidant elements (TBARS, FRAP, GSH and Sulfhydryl groups) were measured in plasma samples. The phytotherapeutic compound's antioxidant activity was measured by polyphenol and total flavonoid quantification, DPPH, NO, and FRAP method. Our results showed that the vehicle influenced some of the results that may have physiological relevance in Chagas disease. However, an important action of M. nigra tincture was observed in the progression of Chagas disease, since our results demonstrated a reduction in parasitemia of treated groups when compared to controls, especially in the group receiving 25 µL. However, in the chronic phase, the 50-µL dosage presented a better activity on some antioxidant defenses and minimized the tissue inflammatory process. Results indicated an important action of M. nigra tincture on the Chagas disease progression.

  5. Gender hormones and the progression of experimental polycystic kidney disease.

    Science.gov (United States)

    Stringer, Kenneth D; Komers, Radko; Osman, Shukri A; Oyama, Terry T; Lindsley, Jessie N; Anderson, Sharon

    2005-10-01

    Male gender is a risk factor for progression of autosomal-dominant polycystic kidney disease (ADPKD), clinically and in the Han:SPRD rat model. Orchiectomy limits progression, but mechanisms of the detrimental effect of androgen, and/or beneficial effects of estrogen, are not known. This protocol tested the hypothesis that male gender (intact androgen status) promotes progression, while female gender (intact estrogen status) is protective; and that these disease-modifying effects are due to changes in expression of known fibrotic mediators. Studies were performed in male and female noncystic control (+/+) and cystic (+/-) rats subjected to orchiectomy, ovariectomy, or sham operation. At 12 weeks of age, renal function was measured. Blood and kidneys were taken for measurement of plasma and renal renin, endothelin (ET-1), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF), using biochemical, protein expression, and immunohistochemical methods. Cystic male rats exhibited significantly reduced glomerular filtration (GFR) and effective renal plasma flow (ERPF) rates, with suppression of plasma and renal renin, up-regulation of renal ET-1 and eNOS, and down-regulation of renal VEGF expression. Orchiectomy attenuated the fall in GFR and ERPF, while numerically limiting changes in eNOS and VEGF. Female rats exhibited less cystic growth, with normal renin status, lesser elevation of renal ET-1, and proportionately lesser changes in VEGF and eNOS. Ovariectomy led to higher blood pressure and reduced GFR and ERPF, with a trend toward upregulation of ET-1, and significant down-regulation of VEGF and eNOS. Female gender is protective, but ovariectomy attenuates the protective effect of female gender, in association with changes in renal expression of ET-1, VEGF, and eNOS. The accelerated disease in male rats can be attenuated by orchiectomy and consequent changes in expression of disease mediators.

  6. Biomarkers of Renal Disease and Progression in Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    Radovan Hojs

    2015-05-01

    Full Text Available Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase, markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

  7. Disease progression of acute pancreatitis in pediatric patients.

    Science.gov (United States)

    Hao, Fabao; Guo, Hongjie; Luo, Qianfu; Guo, Chunbao

    2016-05-15

    Approximately 10% of patients with acute pancreatitis (AP) progress to chronic pancreatitis. Little is known about the factors that affect recurrence of pancreatitis after an initial episode. We retrospectively investigated patients with AP, focusing on their outcomes and the predictors for disease progression. Between July 2003 and June 2015, we retrospectively enrolled first-time AP patients with medical records on disease etiology, severity (according to the Atlanta classifications), and recurrence of AP. Independent predictors of recurrent AP (RAP) and chronic pancreatitis were identified using the logistic regression model. Of the total 159 patients, 45 (28.3%) developed RAP, including two episodes of RAP in 19 patients, and 9 (5.7%) developed chronic pancreatitis. The median duration from the time of AP to the onset of RAP was 5.6 ± 2.3 months. RAP patients were identified as more common among patients with idiopathic first-time AP. The presence of severe ascites, pancreatic necrosis, and systemic complications was independent predictors of RAP in pediatric patients. Experiencing over two RAP episodes was the predictor for developing chronic pancreatitis. No influence of age or number of AP episodes was found on the occurrence of abdominal pain, pain severity, and the prevalence of any pain. Severity of first-time AP and idiopathic first-time AP are related to RAP. Recurrence increases risk for progression to chronic pancreatitis. The risk of recurrence increased with increasing numbers of AP episodes. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Exploiting Novel Radiation-Induced Electromagnetic Material Changes for Remote Detection and Monitoring: Final Progress Report

    Science.gov (United States)

    2016-04-01

    Exploiting Novel Radiation -Induced Electromagnetic Material Changes for Remote Detection and Monitoring: Final Progress Report Distribution...assess the effects of ionizing radiation on at least three classes of electromagnetic materials. The proposed approach for radiation detection was...that was desired to be monitored remotely. Microwave or low millimeter wave electromagnetic radiation would be used to interrogate the device

  9. Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans.

    Science.gov (United States)

    Li, Shan; Ganguli-Indra, Gitali; Indra, Arup K

    2016-05-01

    Lipidomics is the large-scale profiling and characterization of lipid species in a biological system using mass spectrometry. The skin barrier is mainly comprised of corneocytes and a lipid-enriched extracellular matrix. The major skin lipids are ceramides, cholesterol and free fatty acids (FFA). Lipid compositions are altered in inflammatory skin disorders with disrupted skin barrier such as atopic dermatitis (AD). Here we discuss some of the recent applications of lipidomics in human skin biology and in inflammatory skin diseases such as AD, psoriasis and Netherton syndrome. We also review applications of lipidomics in human skin equivalent and in pre-clinical animal models of skin diseases to gain insight into the pathogenesis of the skin disease. Expert commentary: Skin lipidomics analysis could be a fast, reliable and noninvasive tool to characterize the skin lipid profile and to monitor the progression of inflammatory skin diseases such as AD.

  10. Lipoprotein subclasses in the Monitored Atherosclerosis Regression Study (MARS). Treatment effects and relation to coronary angiographic progression.

    Science.gov (United States)

    Mack, W J; Krauss, R M; Hodis, H N

    1996-05-01

    Accumulating evidence suggests that triglyceride-rich lipoproteins contribute to coronary artery disease. Using data from the Monitored Atherosclerosis Regression Study, an angiographic trial of middle-aged men and women randomized to lovastatin or placebo, we investigated relationships between lipoprotein subclasses and progression of coronary artery atherosclerosis. Coronary artery lesion progression was determined by quantitative coronary angiography in low-grade ( or = 50% diameter stenosis), and all coronary artery lesions in 220 baseline/2-year angiogram pairs. Analytical ultracentrifugation was used to measure lipoprotein masses that were statistically evaluated for treatment group differences and relationships to progression of coronary artery atherosclerosis. All low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) masses were significantly lowered and all high density lipoprotein (HDL) masses were significantly raised with lovastatin therapy. The mass of smallest LDL (Svedberg flotation rate [Sf] 0 to 3), IDL (Sf 12 to 20), all VLDL subclasses (Sf 20 to 60, Sf 60 to 100, and Sf 100 to 400), and peak LDL flotation rate were significantly related to the progression of coronary artery lesions, specifically low-grade lesions. Greater baseline levels of HDL3, were related to a lower likelihood of coronary artery lesion progression. In multivariate analyses, small VLDL (Sf 20 to 60) and HDL3 mass were the most important correlates of coronary artery lesion progression. These results provide further evidence for the importance of triglyceride-rich lipoproteins in the progression of coronary artery disease. In addition, these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions. More specific information on coronary artery lesion progression may be obtained through the study of specific apolipoprotein B-containing lipoproteins.

  11. Celiac disease: progress towards diagnosis and definition of pathogenic mechanisms.

    Science.gov (United States)

    Rossi, Mauro; Bot, Adrian

    2011-08-01

    The current issue of the International Reviews of Immunology is dedicated entirely to Celiac Disease (CD). Recent development of additional biomarkers and diagnostics resulted in a sharp revision of the prevalence of this condition, with a previously unrecognized subclinical occurrence in the adult population. This was paralleled by groundbreaking progress in understanding its molecular pathogenesis: while gluten-derived peptides activate the innate immunity, post-translationally modified gluten elicits an adaptive immunity. These arms amplify each other, resulting in a self- perpetuating autoimmune condition, influenced by disturbances of the gut flora and mucus chemistry. The process evolves dramatically in a subset of patients with vulnerable immune homeostasis (eg. Treg cells) explaining the progressive, aggravating syndrome in the clinically overt version of CD. In depth understanding of the pathogenesis of CD thus creates the premises of developing novel, more accurate animal models that should support a rationale development of new prophylactic and therapeutic interventions.

  12. Adult polyglucosan body disease presenting as a unilateral progressive plexopathy.

    Science.gov (United States)

    Naddaf, Elie; Kassardjian, Charles D; Kurt, Yasemin Gulcan; Akman, Hasan Orhan; Windebank, Anthony J

    2016-06-01

    Adult polyglucosan body disease (APBD) usually presents with progressive spastic paraparesis, neurogenic bladder, and distal lower limb sensory abnormalities. It is caused by mutations in the glycogen branching enzyme gene (GBE1). We describe a woman with an unusual phenotype manifesting as progressive left brachial more than lumbosacral plexopathies, with central sensory and corticospinal tract involvement. Magnetic resonance imaging of the brain and cervical spine showed abnormal T2 signal within the ventral pons and medulla bilaterally, involving the pyramidal tracts and the medial leminisci. There was also medullary and cervical spine atrophy. On nerve biopsy, large polyglucosan bodies were noted in the endoneurium. The patient was found to be compound heterozygous for 2 novel mutations in GBE1. Peripheral blood leukocyte GBE activity was markedly reduced to 7% of normal, confirming the diagnosis of APBD. In this report we describe a new phenotype of APBD associated with 2 novel mutations. Muscle Nerve 53: 976-981, 2016. © 2016 Wiley Periodicals, Inc.

  13. Disease Progression in a Patient with Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Ping-Huei Tseng

    2008-10-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is a severe form of nonalcoholic fatty liver disease (NAFLD. The prevalence and clinical significance of NAFLD/NASH have been increasingly recognized in Western countries but much less known in Asian countries, including Taiwan. Here, we report the case of a 43-year-old man who had abnormal liver tests for 18 years. Retrospective evaluation of his initial clinical, laboratory and histologic findings indicated that the hepatic disorder was compatible with the diagnosis of NASH. Although his liver biochemical tests improved after taking lipid-lowering agents, a liver biopsy 17 years later demonstrated histologic progression of intralobular necroinflammation and perivenular fibrosis. These facts suggest that NASH, albeit mild and slowly progressive, indeed exists in Taiwan. After the control of chronic hepatitis B and C and westernization of the lifestyle in Taiwan, an increasing burden of NAFLD/NASH is anticipated and active prophylactic measures should be implemented.

  14. [Fundus autofluorescence in dry AMD - impact on disease progression].

    Science.gov (United States)

    Vidinova, C N; Gouguchkova, P T; Vidinov, K N

    2013-11-01

    Fundus autofluorescence is a novel technique that gives us information about the RPE cells by evaluating the distribution of lipofuscin in the retina. The purpose of our study was to evaluate the diagnostic abilities of OCT, RTVue and fundus autofluorescence in predicting the progression of dry AMD. In our study 37 dry AMD patients were enrolled: 22 of them with druses and 15 with developed geographic atrophy. They all underwent complete ophthalmological examinations including OCT and autofluorescence. We used the RTVue OCT programmes HD line, Cross line, EMM5 and EMM5 progression in all cases. The autofluorescence was recorded with the help of the Canon CX1 fundus camera. OCT images in the AMD patients with dry AMD and large druses showed typical undulations in the RPE/choroid line and occasionally drusenoid detachment of the RPE. Autofluorescence showed different patterns. The confluent reticular autofluorescence was associated with the development of neovascular membranes. In geographic atrophy patient OCTs showed diminished retinal thickness measured with EMM5. On autofluorescence the findings at the border zone atrophic/normal retina were of particular importance. The diffuse increased autofluorescence in that area was considered to be a sign for further atrophy progression. Our results point out that OCT in combination with autofluorescence is important in following the progression of dry AMD. Pathological autofluorescence at the border of atrophic lesions is an important sign for disease activity. Although both OCT and autofluorescence visualise the changes in RPE, autofluorescence is of key importance in predicting the development of the disease. Georg Thieme Verlag KG Stuttgart · New York.

  15. Homeostasis of metals in the progression of Alzheimer's disease.

    Science.gov (United States)

    González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

    2014-06-01

    In order to study the involvement of metals in the progression of Alzheimer's disease, serum samples from patients with Alzheimer and mild cognitive impairment were investigated. For this purpose, metal content was analyzed after size-fractionation of species and then, inter-element and inter-fraction ratios were computed. In this way, the analysis allowed discovering changes that could be used as markers of disease, but also provided a new insight into the interactions in the homeostasis of elements in neurodegeneration and its progression. Aluminum and labile forms of iron and copper were increased in demented patients, while manganese, zinc and selenium were reduced. Interestingly, levels of different elements, principally iron, aluminum and manganese, were closely inter-related, which could evidence a complex interdependency between the homeostasis of the different metals in this disorder. On the other hand, imbalances in metabolism of copper, zinc and selenium could be associated to abnormal redox status. Therefore, this study may contribute to our understanding of the pathological mechanisms related to metals in Alzheimer's disease.

  16. Orphan drugs in development for Huntington's disease: challenges and progress

    Directory of Open Access Journals (Sweden)

    Burgunder JM

    2015-02-01

    Full Text Available Jean-Marc Burgunder1–4 1Swiss Huntington’s Disease Centre, Department of Neurology, University of Bern, Bern, Switzerland; 2Department of Neurology, West China Hospital, Sichuan University, Chengdu, 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, 4Department of Neurology, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Huntington’s disease is a monogenic disorder encompassing a variable phenotype with progressive cognitive, psychiatric, and movement disorders. Knowledge of the mechanisms involved in this disorder has made substantial advances since the discovery of the gene mutation. The dynamic mutation is the expansion of a CAG (cytosine-adenine-guanine repeat in the huntingtin (HTT gene, which is transcribed into an abnormal protein with an elongated polyglutamine tract. Polyglutamine HTT accumulates and is changed in its function in multifaceted ways related to the numerous roles of the normal protein. The protein is expressed in numerous areas of the brain and also in other organs. The major brain region involved in the disease process is the striatum, but it is clear that other systems are involved as well. This accumulated knowledge has now led to the development of treatment strategies based on specific molecular pathways for symptomatic and disease course-modifying treatment. The most proximal way to handle the disturbed protein is to hinder the gene transcription, translation, and/or to increase protein clearance. Other mechanisms now being approached include modulation of energy and intracellular signaling, induction of factors potentially leading to neuroprotection, as well as modulation of glial function. Several clinical trials based on these approaches are now under way, and it is becoming clear that a future disease-modifying therapy will be a combination of several approaches harmonized with symptomatic treatments. In this review, some of the most promising and

  17. Immune evasion mechanisms of Entamoeba histolytica: progression to disease

    Directory of Open Access Journals (Sweden)

    Sharmin eBegum

    2015-12-01

    Full Text Available Entamoeba histolytica (Eh is a protozoan parasite that infects 10% of the world’s population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  18. Immune Evasion Mechanisms of Entamoeba histolytica: Progression to Disease.

    Science.gov (United States)

    Begum, Sharmin; Quach, Jeanie; Chadee, Kris

    2015-01-01

    Entamoeba histolytica (Eh) is a protozoan parasite that infects 10% of the world's population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO) production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells) that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  19. Parkinsonian syndroms: Clinical phenotype, differential diagnosis and disease progression

    International Nuclear Information System (INIS)

    Storch, A.

    2002-01-01

    Parkinsonian syndromes include idiopathic Parkinson's disease (IPD), other neurodegenerative diseases with parkinsonism, the so-called atypical parkinsonian syndromes, and symptomatic parkinsonian syndromes, such as Wilson's disease. IPD is the most frequent disease with parkinsonism as the main clinical feature and is responsible for approx. 80% of all parkinsonian syndromes. Atypical parkinsonian syndromes are the most important differential diagnoses of IPD. The two most frequent types are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). For clinical diagnosis it is essential to take a careful medical history and to examine the patients physically in regular intervals. However, various clinico-pathological studies have shown that approx. 25% of patients with clinical diagnosis of IPD may have other causes of parkinsonism. Selected technical investigations, in particular functional imaging of the central dopaminergic system using PET or SPECT, may help to make clinical diagnosis more secure. This paper reviews the clinical features and diagnostic findings in diseases with parkinsonism and summarises the difficulties in establishing early and differential diagnoses. (orig.) [de

  20. Semantic Memory in the Clinical Progression of Alzheimer Disease.

    Science.gov (United States)

    Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

    2017-09-01

    Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

  1. Geothermal progress monitor. Progress report No. 3, March-April 1980

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-01

    Progress is reviewed in the following areas: electric uses; direct heat uses; drilling activities; exploration; leases; outreach and technical assistance; feasibility studies and application demonstrations; geothermal loan guarantee program; general activities; R and D activities; legal, institutional, and regulatory activities; environmental activities; and state, local, and private sector activities. Also included are a list of reports and publications and a directory of individuals in the geothermal community. (MHR)

  2. Progress report of the critical equipment monitoring system

    International Nuclear Information System (INIS)

    Pantis, M.J.

    1984-01-01

    The Philadelphia Electric Company has contracted with Energy Data Systems to develop a Critical Equipment Monitoring System for its Peach Bottom Nuclear Plant. This computerized system is designed to acquire and maintain accurate and timely status information on plant equipment. It will provide auditable record of plant and equipment transactions. Positive equipment identification and location will be provided. Errors in complex logical checking will be minimized. This system should reduce operator loading and improve operator communicatin with the plant personnel. Phase I of this system was installed at Peach Bottom Nuclear Station May 1982. It provides the necessary hardware and software to do check-off lists on critical plant systems. This paper describes some of the start-up and operational problems encountered

  3. Monitoring of Progressive Damage in Buildings Using Laser Scan Data

    Science.gov (United States)

    Puente, I.; Lindenbergh, R.; Van Natijne, A.; Esposito, R.; Schipper, R.

    2018-05-01

    Vulnerability of buildings to natural and man-induced hazards has become a main concern for our society. Ensuring their serviceability, safety and sustainability is of vital importance and the main reason for setting up monitoring systems to detect damages at an early stage. In this work, a method is presented for detecting changes from laser scan data, where no registration between different epochs is needed. To show the potential of the method, a case study of a laboratory test carried out at the Stevin laboratory of Delft University of Technology was selected. The case study was a quasi-static cyclic pushover test on a two-story high unreinforced masonry structure designed to simulate damage evolution caused by cyclic loading. During the various phases, we analysed the behaviour of the masonry walls by monitoring the deformation of each masonry unit. First a plane is fitted to the selected wall point cloud, consisting of one single terrestrial laser scan, using Principal Component Analysis (PCA). Second, the segmentation of individual elements is performed. Then deformations with respect to this plane model, for each epoch and specific element, are determined by computing their corresponding rotation and cloud-to-plane distances. The validation of the changes detected within this approach is done by comparison with traditional deformation analysis based on co-registered TLS point clouds between two or more epochs of building measurements. Initial results show that the sketched methodology is indeed able to detect changes at the mm level while avoiding 3D point cloud registration, which is a main issue in computer vision and remote sensing.

  4. Idaho Steelhead Monitoring and Evaluation Studies : Annual Progress Report 2007.

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Timothy; Putnam, Scott

    2008-12-01

    The goal of Idaho Steelhead Monitoring and Evaluation Studies is to collect monitoring data to evaluate wild and natural steelhead populations in the Clearwater and Salmon river drainages. During 2007, intensive population data were collected in Fish Creek (Lochsa River tributary) and Rapid River (Little Salmon River tributary); extensive data were collected in other selected spawning tributaries. Weirs were operated in Fish Creek and Rapid River to estimate adult escapement and to collect samples for age determination and genetic analysis. Snorkel surveys were conducted in Fish Creek, Rapid River, and Boulder Creek (Little Salmon River tributary) to estimate parr density. Screw traps were operated in Fish Creek, Rapid River, Secesh River, and Big Creek to estimate juvenile emigrant abundance, to tag fish for survival estimation, and to collect samples for age determination and genetic analysis. The estimated wild adult steelhead escapement in Fish Creek was 81 fish and in Rapid River was 32 fish. We estimate that juvenile emigration was 24,127 fish from Fish Creek; 5,632 fish from Rapid River; and 43,674 fish from Big Creek. The Secesh trap was pulled for an extended period due to wildfires, so we did not estimate emigrant abundance for that location. In cooperation with Idaho Supplementation Studies, trap tenders PIT tagged 25,618 steelhead juveniles at 18 screw trap sites in the Clearwater and Salmon river drainages. To estimate age composition, 143 adult steelhead and 5,082 juvenile steelhead scale samples were collected. At the time of this report, 114 adult and 1,642 juvenile samples have been aged. Project personnel collected genetic samples from 122 adults and 839 juveniles. We sent 678 genetic samples to the IDFG Eagle Fish Genetics Laboratory for analysis. Water temperature was recorded at 37 locations in the Clearwater and Salmon river drainages.

  5. The role of acquired immunity and periodontal disease progression.

    Science.gov (United States)

    Teng, Yen-Tung A

    2003-01-01

    Our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host's immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system not only in fighting the virulent periodontal pathogens but also in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response-in particular, CD4+ T-cells-plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host's tissue destruction. In particular, studies of the pathogen-specific CD4+ T-cell-mediated immunity have clarified the roles of: (i) the relative diverse immune repertoire involved in periodontal pathogenesis, (ii) the contribution of pathogen-associated Th1-Th2 cytokine expressions in periodontal disease progression, and (iii) micro-organism-triggered periodontal CD4+ T-cell-mediated osteoclastogenic factor, 'RANK-L', which is linked to the induction of alveolar bone destruction in situ. The present review will focus on some recent advances in the acquired immune responses involving B-cells, CD8+ T-cells, and CD4+ T-cells in the context of periodontal disease progression. New approaches will further facilitate our understanding of their underlying molecular mechanisms that may lead to the development of new treatment modalities for periodontal diseases and their associated complications.

  6. Evaluating Alzheimer's disease progression using rate of regional hippocampal atrophy.

    Directory of Open Access Journals (Sweden)

    Edit Frankó

    Full Text Available Alzheimer's disease (AD is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

  7. Naturalism about health and disease: adding nuance for progress.

    Science.gov (United States)

    Kingma, Elselijn

    2014-12-01

    The literature on health and diseases is usually presented as an opposition between naturalism and normativism. This article argues that such a picture is too simplistic: there is not one opposition between naturalism and normativism, but many. I distinguish four different domains where naturalist and normativist claims can be contrasted: (1) ordinary usage, (2) conceptually clean versions of "health" and "disease," (3) the operationalization of dysfunction, and (4) the justification for that operationalization. In the process I present new arguments in response to Schwartz (2007) and Hausman (2012) and expose a link between the arguments made by Schwartz (2007) and Kingma (2010). Distinguishing naturalist claims at these four domains will allow us to make progress by (1) providing more nuanced, intermediate positions about a possible role for values in health and disease; and (2) assisting in the addressing of relativistic worries about the value-ladenness of health and disease. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

    Science.gov (United States)

    Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

    2018-01-01

    The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

  9. Progressive microstructural changes of the occipital cortex in Huntington's disease.

    Science.gov (United States)

    Odish, Omar F F; Reijntjes, Robert H A M; van den Bogaard, Simon J A; Roos, Raymund A C; Leemans, Alexander

    2018-02-28

    In this study we longitudinally investigated the rate of microstructural alterations in the occipital cortex in different stages of Huntington's disease (HD) by applying an automated atlas-based approach to diffusion MRI data. Twenty-two premanifest (preHD), 10 early manifest HD (early HD) and 24 healthy control subjects completed baseline and two year follow-up scans. The preHD group was stratified based on the predicted years to disease onset into a far (preHD-A) and near (preHD-B) to disease onset group. Clinical and behavioral measures were collected per assessment time point. An automated atlas-based DTI analysis approach was used to obtain the mean, axial and radial diffusivities of the occipital cortex. We found that the longitudinal rate of diffusivity change in the superior occipital gyrus (SOG), middle occipital gyrus (MOG), and inferior occipital gyrus (IOG) was significantly higher in early HD compared to both preHD and controls (all p's ≤ 0.005), which can be interpreted as an increased rate of microstructural degeneration. Furthermore, the change rate in the diffusivity of the MOG could significantly discriminate between preHD-B compared to preHD-A and the other groups (all p's ≤ 0.04). Finally, we found an inverse correlation between the Stroop Word Reading task and diffusivities in the SOG and MOG (all p's ≤ 0.01). These findings suggest that measures obtained from the occipital cortex can serve as sensitive longitudinal biomarkers for disease progression in preHD-B and early HD. These could in turn be used to assess potential effects of proposed disease modifying therapies.

  10. Environmental factors affecting inflammatory bowel disease: have we made progress?

    Science.gov (United States)

    Lakatos, Peter Laszlo

    2009-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is only partially understood; various environmental and host (e.g. genetic, epithelial, immune, and nonimmune) factors are involved. The critical role for environmental factors is strongly supported by recent worldwide trends in IBD epidemiology. One important environmental factor is smoking. A meta-analysis partially confirms previous findings that smoking was found to be protective against ulcerative colitis and, after the onset of the disease, might improve its course, decreasing the need for colectomy. In contrast, smoking increases the risk of developing Crohn's disease and aggravates its course. The history of IBD is dotted by cyclic reports on the isolation of specific infectious agents responsible for Crohn's disease or ulcerative colitis. The more recently published cold chain hypothesis is providing an even broader platform by linking dietary factors and microbial agents. An additional, recent theory has suggested a breakdown in the balance between putative species of 'protective' versus 'harmful' intestinal bacteria - this concept has been termed dysbiosis resulting in decreased bacterial diversity. Other factors such as oral contraceptive use, appendectomy, dietary factors (e.g. refined sugar, fat, and fast food), perinatal events, and childhood infections have also been associated with both diseases, but their role is more controversial. Nonetheless, there is no doubt that economic development, leading to improved hygiene and other changes in lifestyle ('westernized lifestyle') may play a role in the increase in IBD. This review article focuses on the role of environmental factors in the pathogenesis and progression of IBDs. Copyright 2009 S. Karger AG, Basel.

  11. Fluorescence Lifetime Imaging in Stargardt Disease: Potential Marker for Disease Progression

    OpenAIRE

    Dysli Chantal; Wolf Sebastian; Hatz Katja; Zinkernagel Martin

    2016-01-01

    PURPOSE The purpose of this study was to describe autofluorescence lifetime characteristics in Stargardt disease (STGD) using fluorescence lifetime imaging ophthalmoscopy (FLIO) and to investigate potential prognostic markers for disease activity and progression. METHODS Fluorescence lifetime data of 16 patients with STGD (mean age, 40 years; range, 22-56 years) and 15 age-matched controls were acquired using a fluorescence lifetime imaging ophthalmoscope based on a Heidelberg Eng...

  12. Global gene expression profile progression in Gaucher disease mouse models

    Directory of Open Access Journals (Sweden)

    Zhang Wujuan

    2011-01-01

    Full Text Available Abstract Background Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells in visceral organs and their abnormal functions are obscure. Results To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null. About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change, representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk of INFγ-regulated pro-inflammatory (13 and IL-4-regulated anti-inflammatory (11 cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation. Conclusions Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.

  13. Blood platelets in the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nina S Gowert

    Full Text Available Alzheimer's disease (AD is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA. Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.

  14. Fear of progression in chronic diseases: psychometric properties of the Fear of Progression Questionnaire.

    Science.gov (United States)

    Herschbach, Peter; Berg, Petra; Dankert, Andrea; Duran, Gabriele; Engst-Hastreiter, Ursula; Waadt, Sabine; Keller, Monika; Ukat, Robert; Henrich, Gerhard

    2005-06-01

    The aim of this study was the development and psychometric testing of a new psychological questionnaire to measure the fear of progression (FoP) in chronically ill patients (cancer, diabetes mellitus and rheumatic diseases). The Fear of Progression Questionnaire (FoP-Q) was developed in four phases: (1) generation of items (65 interviews); (2) reduction of items--the initial version of the questionnaire (87 items) was presented to 411 patients, to construct subscales and test the reliability; (3) testing the convergent and discriminative validity of the reduced test version (43 items) within a new sample (n=439); (4) translation--German to English. The scale comprised five factors (Cronbach's alpha >.70): affective reactions (13 items), partnership/family (7), occupation (7), loss of autonomy (7) and coping with anxiety (9). The test-retest reliability coefficients varied between .77 and .94. There was only a medium relationship to traditional anxiety scales. This is an indication of the independence of the FoP. Significant relationships between the FoP-Q and the patient's illness behaviour indicate discriminative validity. The FoP-Q is a new and unique questionnaire developed for the chronically ill. A major problem and source of stress for this patient group has been measuring both specifically and economically the FoP of an illness. The FoP-Q was designed to resolve this problem, fulfill this need and reduce this stress.

  15. [Progressive damage monitoring of corrugated composite skins by the FBG spectral characteristics].

    Science.gov (United States)

    Zhang, Yong; Wang, Bang-Feng; Lu, Ji-Yun; Gu, Li-Li; Su, Yong-Gang

    2014-03-01

    In the present paper, a method of monitoring progressive damage of composite structures by non-uniform fiber Bragg grating (FBG) reflection spectrum is proposed. Due to the finite element analysis of corrugated composite skins specimens, the failure process under tensile load and corresponding critical failure loads of corrugated composite skin was predicated. Then, the non-uniform reflection spectrum of FBG sensor could be reconstructed and the corresponding relationship between layer failure order sequence of corrugated composite skin and FBG sensor reflection spectrums was acquired. A monitoring system based on FBG non-uniform reflection spectrum, which can be used to monitor progressive damage of corrugated composite skins, was built. The corrugated composite skins were stretched under this FBG non-uniform reflection spectrum monitoring system. The results indicate that real-time spectrums acquired by FBG non-uniform reflection spectrum monitoring system show the same trend with the reconstruction reflection spectrums. The maximum error between the corresponding failure and the predictive value is 8.6%, which proves the feasibility of using FBG sensor to monitor progressive damage of corrugated composite skin. In this method, the real-time changes in the FBG non-uniform reflection spectrum within the scope of failure were acquired through the way of monitoring and predicating, and at the same time, the progressive damage extent and layer failure sequence of corru- gated composite skin was estimated, and without destroying the structure of the specimen, the method is easy and simple to operate. The measurement and transmission section of the system are completely composed of optical fiber, which provides new ideas and experimental reference for the field of dynamic monitoring of smart skin.

  16. Incisor malalignment and the risk of periodontal disease progression.

    Science.gov (United States)

    Alsulaiman, Ahmed A; Kaye, Elizabeth; Jones, Judith; Cabral, Howard; Leone, Cataldo; Will, Leslie; Garcia, Raul

    2018-04-01

    The objective of this study was to investigate the association between incisor crowding, irregularity, and periodontal disease progression in the anterior teeth. Data collected over 35 years from men enrolled in the Veterans Affairs Dental Longitudinal Study included information concerning pocket depth and alveolar bone loss. Plaster casts of the maxillary (n = 400) and mandibular (n = 408) arches were available for baseline measurements. Periodontal disease in the anterior teeth was defined as per arch sum of pathologic pocket depth and sum of teeth with any alveolar bone loss in the anterior sextants. Incisor malalignment status was defined by the anterior tooth size-arch length discrepancy index and Little's Irregularity Index. Adjusted mixed effects linear models computed the beta (β) estimates and 95% confidence intervals (95% CI) of the amounts of change in periodontal disease outcomes by the level of malalignment. In the anterior maxillary arch, crowding and spacing were significantly associated with an increased per-arch sum of pathologic pocket depth (β, 0.70 mm; 95% CI, 0.20-1.21, and β, 0.49 mm; 95% CI, 0.06-0.91, respectively). In the anterior mandibular arch, incisor crowding and irregularity were significantly associated with an increased per-arch sum of pathologic pocket depth (mild crowding: β, 0.47 mm; 95% CI, 0.01-0.93; severe irregularity: β, 0.94 mm; 95% CI, 0.50-1.38), and the sum number of teeth with alveolar bone loss (mild and moderate-to-severe crowding: β, 0.45 teeth; 95% CI, 0.08-0.82; and β, 0.45 teeth; 95% CI, 0.13-0.83, respectively; moderate irregularity: β, 0.34 teeth; 95% CI, 0.06-0.62). Certain incisor malalignment traits (ie, maxillary incisor crowding, maxillary incisor spacing, mandibular incisor mild crowding, mandibular incisor moderate-to-severe crowding, mandibular incisor moderate irregularity, and mandibular incisor severe irregularity) are associated with significant periodontal disease progression

  17. Overlap between age-at-onset and disease-progression determinants in Huntington disease.

    Science.gov (United States)

    Aziz, N Ahmad; van der Burg, Jorien M M; Tabrizi, Sarah J; Landwehrmeyer, G Bernhard

    2018-05-09

    A fundamental but still unresolved issue regarding Huntington disease (HD) pathogenesis is whether the factors that determine age at onset are the same as those that govern disease progression. Because elucidation of this issue is crucial for the development as well as optimal timing of administration of novel disease-modifying therapies, we aimed to assess the extent of overlap between age-at-onset and disease-progression determinants in HD. Using observational data from Enroll-HD, the largest cohort of patients with HD worldwide, in this study we present, validate, and apply an intuitive method based on linear mixed-effect models to quantify the variability in the rate of disease progression in HD. A total of 3,411 patients with HD met inclusion criteria. We found that (1) about two-thirds of the rate of functional, motor, and cognitive progression in HD is determined by the same factors that also determine age at onset, with CAG repeat-dependent mechanisms having by far the largest effect; (2) although expanded HTT CAG repeat size had a large influence on average body weight, the rate of weight loss was largely independent of factors that determine age at onset in HD; and (3) about one-third of the factors that determine the rate of functional, motor, and cognitive progression are different from those that govern age at onset and need further elucidation. Our findings imply that targeting of CAG repeat-dependent mechanisms, for example through gene-silencing approaches, is likely to affect the rate of functional, motor, and cognitive impairment, but not weight loss, in manifest HD mutation carriers. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  18. Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review.

    Science.gov (United States)

    Block, Valerie A J; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A C; Allen, Diane D; Gelfand, Jeffrey M

    2016-01-01

    To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability.

  19. Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review

    Science.gov (United States)

    Block, Valerie A. J.; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A. C.; Allen, Diane D.; Gelfand, Jeffrey M.

    2016-01-01

    Objective To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Methods Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. Results 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. Conclusions These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability. PMID:27124611

  20. Actigraphy monitoring of symptoms in patients with Parkinson's disease.

    Science.gov (United States)

    Pan, Weidong; Kwak, Shin; Li, Fuzhong; Wu, Chunlan; Chen, Yiyun; Yamamoto, Yoshiharu; Cai, Dingfang

    2013-07-02

    Although the Unified Parkinson's Disease Rating Scale (UPDRS) is the "gold-standard" tool in assessing the severity of symptoms in patients with Parkinson's disease (PD), not all activity-related disease symptoms can be accurately captured by the well-established clinical rating scale. Using an alternative approach, this study examined the level of physical activity measured by actigraphy over time and whether change in physical activity was associated with disease severity assessed by UPDRS. We used a longitudinal design in which physical activity and disease severity were assessed repeatedly during a 4-month interval, over a 3-year observational period, in a sample of 61 patients with idiopathic PD and a control group of 32 neurologically intact individuals. Physical activity data during awake-time were analyzed using the power-law exponent (PLE) method. Correlational relationships between changes in maxima values of PLE and scores of total UPDRS, UPDRS-part II (Activities of Daily Living), and UPDRS-part III (Motor Examination) in patients with PD were examined. Results show an increase in maxima values of PLE and the UPDRS total score in PD patients and that there is a positive association between changes in maxima values and total UPDRS score (r=0.746, p=0.032), UPDRS-part II score (r=0.687, p=0.027), and UPDRS-part III score (r=0.893, p=0.018). There was no significant change in the level of physical activity over time for the controls. Findings from this study indicate that change in physical activity, as captured by actigraphy, is associated with increased severity in patients' clinical symptoms of PD over time. Thus, these data suggest that, when used in conjunction with the conventional UPDRS measure, an actigraphic measure of physical activity may provide clinicians an adjunct measurement approach to monitor patients' activity-based disease progression or responses to treatment in outpatient clinic settings. Copyright © 2013 The Authors. Published by

  1. Disease management: atrial fibrillation and home monitoring.

    Science.gov (United States)

    Ricci, Renato Pietro

    2013-06-01

    Device-detected atrial fibrillation (AF) episodes predict poor clinical outcome regardless of symptoms. Potential benefits of remote monitoring are early arrhythmia detection and patient continuous monitoring. Several studies of device remote monitoring consistently demonstrated that AF represents the most common clinical alert and that detailed information on arrhythmia onset, duration, and burden as well as on the ventricular rate may be early available for clinical evaluation. Reaction time to AF alerts was very short in all series involving either pacemakers or defibrillators and action ability of AF alerts was very high. In the Home Guide Registry, in which 1650 patients were enrolled, AF was detected in 16.3% of patients and represented 36% of all cardiovascular events during the follow-up. Timely anticoagulation introduction in asymptomatic patients may impact on the stroke rate. According to the results of repeated Monte Carlo simulations based on a real population of 166 patients, daily monitoring may reduce the 2-year stroke risk by 9-18% with an absolute reduction of 0.2-0.6%, compared with conventional inter-visit intervals of 6-12 months. In the COMPAS trial, the incidence of hospitalizations for atrial arrhythmias and related stroke was significantly higher in the control group than in the remote monitoring group. Major questions will be addressed by the ongoing IMPACT trial in which a remote monitoring guided anticoagulation strategy based on AF detection will be compared with a physician-directed standard strategy. In patients with heart failure, AF early detection combined with other indexes may help prevent hospitalizations.

  2. Plasma viscosity increase with progression of peripheral arterial atherosclerotic disease.

    Science.gov (United States)

    Poredos, P; Zizek, B

    1996-03-01

    -macroglobulin (r=0.78, P < 0.01). These results indicate that in patients with peripheral arterial disease plasma viscosity increases with the progression of the atherosclerotic process and is correlated with the clinical stages of the disease.

  3. Hypoxemia in patients with COPD: cause, effects, and disease progression.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation\\/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.

  4. "Work in progress" : the hidden dimensions of monitoring and planning in Pakistan

    NARCIS (Netherlands)

    Kolkma, W.A.M.

    1998-01-01

    The study argues that monitoring systems for large numbers of projects constituting public sector development programmes such as found in Pakistan, are built on the positivist premise that progress can be summarised objectively and in a few concise statements or indicators. Theory and

  5. Using Parents and Teachers to Monitor Progress among Children with ASD: A Review of Intervention Research

    Science.gov (United States)

    Witmer, Sara E.; Nasamran, Amy; Parikh, Purvi J.; Schmitt, Heather A.; Clinton, Marianne C.

    2015-01-01

    Despite growing knowledge of the effectiveness of various interventions for children with autism spectrum disorders (ASD), it is never clear whether a particular intervention will be effective for a specific child with ASD. Careful monitoring of an individual child's progress is necessary to know whether an intervention is effective. In this…

  6. Costing Household Surveys for Monitoring Progress Toward Ending Extreme Poverty and Boosting Shared Prosperity

    OpenAIRE

    Kilic, Talip; Serajuddin, Umar; Uematsu, Hiroki; Yoshida, Nobuo

    2017-01-01

    On October 15, 2015, World Bank Group President Jim Yong Kim announced the World Bank Group’s commitment to support the 78 poorest countries to implement a multi-topic household survey every three years between 2016 and 2030, for monitoring progress toward ending extreme poverty and boosting shared prosperity. This paper estimates the resource requirements to achieve the objectives of impl...

  7. Progress on conformal microwave array applicators for heating chestwall disease

    Science.gov (United States)

    Stauffer, P. R.; Maccarini, P. F.; Juang, T.; Jacobsen, S. K.; Gaeta, C. J.; Schlorff, J. L.; Milligan, A. J.

    2007-02-01

    Previous studies have reported the computer modeling, CAD design, and theoretical performance of single and multiple antenna arrays of Dual Concentric Conductor (DCC) square slot radiators driven at 915 and 433 MHz. Subsequently, practical CAD designs of microstrip antenna arrays constructed on thin and flexible printed circuit board (PCB) material were reported which evolved into large Conformal Microwave Array (CMA) sheets that could wrap around the surface of the human torso for delivering microwave energy to large areas of superficial tissue. Although uniform and adjustable radiation patterns have been demonstrated from multiple element applicators radiating into simple homogeneous phantom loads, the contoured and heterogeneous tissue loads typical of chestwall recurrent breast cancer have required additional design efforts to achieve good coupling and efficient heating from the increasingly larger conformal array applicators used to treat large area contoured patient anatomy. Thus recent work has extended the theoretical optimization of DCC antennas to improve radiation efficiency of each individual aperture and reduce mismatch reflections, radiation losses, noise, and cross coupling of the feedline distribution network of large array configurations. Design improvements have also been incorporated into the supporting bolus structure to maintain effective coupling of DCC antennas into contoured anatomy and to monitor and control surface temperatures under the entire array. New approaches for non-invasive monitoring of surface and sub-surface tissue temperatures under each independent heat source are described that make use of microwave radiometry and flexible sheet grid arrays of thermal sensors. Efforts to optimize the clinical patient interface and move from planar rectangular shapes to contoured vest applicators that accommodate entire disease in a larger number of patients are summarized. By applying heat more uniformly to large areas of contoured anatomy

  8. Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

    Science.gov (United States)

    Bradbury, Allison M; Gray-Edwards, Heather L; Shirley, Jamie L; McCurdy, Victoria J; Colaco, Alexandria N; Randle, Ashley N; Christopherson, Pete W; Bird, Allison C; Johnson, Aime K; Wilson, Diane U; Hudson, Judith A; De Pompa, Nicholas L; Sorjonen, Donald C; Brunson, Brandon L; Jeyakumar, Mylvaganam; Platt, Frances M; Baker, Henry J; Cox, Nancy R; Sena-Esteves, Miguel; Martin, Douglas R

    2014-01-01

    The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated GM2 patients and those in future clinical trials. PMID:25284324

  9. Perspective Insights into Disease Progression, Diagnostics, and Therapeutic Approaches in Alzheimer's Disease: A Judicious Update

    Directory of Open Access Journals (Sweden)

    Arif Tasleem Jan

    2017-11-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and−2 genes. AD progresses through accumulation of amyloid plaques (Aβ and neurofibrillary tangles (NFTs in brain, which interfere with neuronal communication. Cellular stress that arises through mitochondrial dysfunction, endoplasmic reticulum malfunction, and autophagy contributes significantly to the pathogenesis of AD. With high accuracy in disease diagnostics, Aβ deposition and phosphorylated tau (p-tau are useful core biomarkers in the cerebrospinal fluid (CSF of AD patients. Although five drugs are approved for treatment in AD, their failures in achieving complete disease cure has shifted studies toward a series of molecules capable of acting against Aβ and p-tau. Failure of biologics or compounds to cross the blood-brain barrier (BBB in most cases advocates development of an efficient drug delivery system. Though liposomes and polymeric nanoparticles are widely adopted for drug delivery modules, their use in delivering drugs across the BBB has been overtaken by exosomes, owing to their promising results in reducing disease progression.

  10. Wireless Monitoring for Patients with Cardiovascular Diseases and Parkinson's Disease.

    Science.gov (United States)

    Kefaliakos, Antonios; Pliakos, Ioannis; Charalampidou, Martha; Diomidous, Marianna

    2016-01-01

    The use of applications for mobile devices and wireless sensors is common for the sector of telemedicine. Recently various studies and systems were developed in order to help patients suffering from severe diseases such as cardiovascular diseases and Parkinson's disease. They present a challenge for the sector because such systems demand the flow of accurate data in real time and the use of specialized sensors. In this review will be presented some very interesting applications developed for patients with cardiovascular diseases and Parkinson's disease.

  11. Decreased RECQL5 correlated with disease progression of osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Junlong; Zhi, Liqiang; Dai, Xin; Cai, Qingchun; Ma, Wei, E-mail: doctormawei@163.com

    2015-11-27

    Human RecQ helicase family, consisting of RECQL, RECQL4, RECQL5, BLM and WRN, has critical roles in genetic stability and tumorigenesis. Although RECQL5 has been reported to correlate with the susceptibility to malignances including osteosarcoma, the specific effect on tumor genesis and progression is not yet clarified. Here we focused on the relationship between RECQL5 expression and osteosarcoma disease progression, and further investigated the function of RECQL5 on MG-63 cell proliferation and apoptosis. By immunohistochemical analysis, qRT-PCR and western blot, we found that RECQL5 expression was downregulated in osteosarcoma tissues and cells. Patients with advanced tumor stage and low grade expressed lower RECQL5. To construct a stable RECQL5 overexpression osteosarcoma cell line (MG-63-RECQL5), RECQL5 gene was inserted into the human AAVS1 safe harbor by CRISPR/Cas9 system. The overexpression of RECQL5 was verified by qRT-PCR and western blot. Cell proliferation, cell cycle and apoptosis assay revealed that RECQL5 overexpression inhibited proliferation, induced G1-phase arrest and promoted apoptosis in MG-63 cells. Collectively, our results suggested RECQL5 as a tumor suppressor in osteosarcoma and may be a potential therapeutic target for osteosarcoma treatment. - Highlights: • The expression of RECQL5 was downregulated in osteosarcoma tissues and cells. • Decreased RECQL5 correlated with osteosarcoma Enneking surgical classification. • We constructed a stable RECQL5 overexpression cell line by CRISPR/Cas9 system. • RECQL5 overexpression inhibited proliferation of MG-63 cells. • RECQL5 overexpression promoted apoptosis of MG-63 cells.

  12. Decreased RECQL5 correlated with disease progression of osteosarcoma

    International Nuclear Information System (INIS)

    Wu, Junlong; Zhi, Liqiang; Dai, Xin; Cai, Qingchun; Ma, Wei

    2015-01-01

    Human RecQ helicase family, consisting of RECQL, RECQL4, RECQL5, BLM and WRN, has critical roles in genetic stability and tumorigenesis. Although RECQL5 has been reported to correlate with the susceptibility to malignances including osteosarcoma, the specific effect on tumor genesis and progression is not yet clarified. Here we focused on the relationship between RECQL5 expression and osteosarcoma disease progression, and further investigated the function of RECQL5 on MG-63 cell proliferation and apoptosis. By immunohistochemical analysis, qRT-PCR and western blot, we found that RECQL5 expression was downregulated in osteosarcoma tissues and cells. Patients with advanced tumor stage and low grade expressed lower RECQL5. To construct a stable RECQL5 overexpression osteosarcoma cell line (MG-63-RECQL5), RECQL5 gene was inserted into the human AAVS1 safe harbor by CRISPR/Cas9 system. The overexpression of RECQL5 was verified by qRT-PCR and western blot. Cell proliferation, cell cycle and apoptosis assay revealed that RECQL5 overexpression inhibited proliferation, induced G1-phase arrest and promoted apoptosis in MG-63 cells. Collectively, our results suggested RECQL5 as a tumor suppressor in osteosarcoma and may be a potential therapeutic target for osteosarcoma treatment. - Highlights: • The expression of RECQL5 was downregulated in osteosarcoma tissues and cells. • Decreased RECQL5 correlated with osteosarcoma Enneking surgical classification. • We constructed a stable RECQL5 overexpression cell line by CRISPR/Cas9 system. • RECQL5 overexpression inhibited proliferation of MG-63 cells. • RECQL5 overexpression promoted apoptosis of MG-63 cells.

  13. Progressive diaphyseal dysplasia (Engelmann's disease) - Report of a case -

    International Nuclear Information System (INIS)

    Soh, M. H.; Rhee, S. J.; Won, J. J.

    1981-01-01

    Progressive diaphyseal dysplasia is a rare condition and radiographic finding provides conclusive proof. We have experienced a sporadic case of progressive disphyseal dysplasia (Engelmann's disease) of 8 year-old-Korean girl, confirmed by radiographic skeletal survey and biopsy. This patient was admitted to the Jeonbug National University Hospital because of painful swelling of the distal part of the right femur after trauma and intermittent pain in her lower legs with a peculiar wadding gait for 2 years. On a physical examination, the patient appeared thin and slender. The skeletal musculature was poorly developed and the upper and lower extremities were weak. She walked with a peculiar wadding gait. The height was normal. No joint abnormality was noted and the mental state was alert. The child was the product of a normal gestation and delivery. Radiographic studies of the skeleton showed a generalized and symmetrical distribution of the bone characterized by cortical thickening, fusiform enlargement, and a narrowed medullary cavity in the diaphyseal of long bones while the epiphyses and metaphyses was not involved. Abrupt demarcation of the lesion with loss of normal trabecular pattern was note. Elongation of the extremities relative to the size of the child was present. The above radiographic findings showed involvement of all the long tubular bones such as the ulna, radius, tibia, fibula, femur and humerus. A sight sclerosis of the base of her skull was present, but the calvarium was not involved. The hands, feet, pelvis, spine, clavicle, rib, scapula and mandible were not affected. There was no specific laboratory finding except for the slightly elevated ESR. Histological examination of the bone biopsies from the femur revealed thickening of periosteum and proliferation of the walls of the small arterioles with reduction in the size of the lumen. The bony cortex showed essentially normal bone with the increased osteoblastic and osteoclastic activity

  14. An advanced case of indium lung disease with progressive emphysema.

    Science.gov (United States)

    Nakano, Makiko; Tanaka, Akiyo; Hirata, Miyuki; Kumazoe, Hiroyuki; Wakamatsu, Kentaro; Kamada, Dan; Omae, Kazuyuki

    2016-09-30

    To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 μg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV 1 ) of 3.19 l (80.8% of predicted), and an FEV 1 -to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m 3 . In 2009, the subject's In-S had increased to 132.1 μg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option.

  15. Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Singh S

    2014-08-01

    Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

  16. Parkinson disease and progressive supranuclear palsy: protein expression in skin.

    Science.gov (United States)

    Rodríguez-Leyva, Ildefonso; Chi-Ahumada, Erika G; Carrizales, Juan; Rodríguez-Violante, Mayela; Velázquez-Osuna, Salvador; Medina-Mier, Verónica; Martel-Gallegos, María G; Zarazúa, Sergio; Enríquez-Macías, Lourdes; Castro, Adriana; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E

    2016-03-01

    This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP. We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis. The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs. These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.

  17. Bicarbonate therapy for prevention of chronic kidney disease progression.

    Science.gov (United States)

    Łoniewski, Igor; Wesson, Donald E

    2014-03-01

    Kidney injury in chronic kidney disease (CKD) is likely multifactorial, but recent data support that a component is mediated by mechanisms used by the kidney to increase acidification in response to an acid challenge to systemic acid-base status. If so, systemic alkalization might attenuate this acid-induced component of kidney injury. An acid challenge to systemic acid-base status increases nephron acidification through increased production of endothelin, aldosterone, and angiotensin II, each of which can contribute to kidney inflammation and fibrosis that characterizes CKD. Systemic alkalization that ameliorates an acid challenge might attenuate the contributions of angiotensin II, endothelin, and aldosterone to kidney injury. Some small clinical studies support the efficacy of alkalization in attenuating kidney injury and slowing glomerular filtration rate decline in CKD. This review focuses on the potential that orally administered NaHCO₃ prevents CKD progression and additionally addresses its mechanism of action, side effects, possible complications, dosage, interaction, galenic form description, and contraindications. Current National Kidney Foundation guidelines recommend oral alkali, including NaHCO₃(-), in CKD patients with serum HCO₃(-) <22 mmol/l. Although oral alkali can be provided by other medications and by base-inducing dietary constituents, oral NaHCO₃ will be the focus of this review because of its relative safety and apparent efficacy, and its comparatively low cost.

  18. Brain correlates of progressive olfactory loss in Parkinson's disease.

    Science.gov (United States)

    Campabadal, Anna; Uribe, Carme; Segura, Barbara; Baggio, Hugo C; Abos, Alexandra; Garcia-Diaz, Anna Isabel; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Bargallo, Nuria; Junque, Carme

    2017-08-01

    Olfactory dysfunction is present in a large proportion of patients with Parkinson's disease (PD) upon diagnosis. However, its progression over time has been poorly investigated. The few available longitudinal studies lack control groups or MRI data. To investigate the olfactory changes and their structural correlates in non-demented PD over a four-year follow-up. We assessed olfactory function in a sample of 25 PD patients and 24 normal controls of similar age using the University of Pennsylvania Smell Identification test (UPSIT). Structural magnetic resonance imaging data, obtained with a 3-T Siemens Trio scanner, were analyzed using FreeSurfer software. Analysis of variance showed significant group (F = 53.882; P effects, but the group-by-time interaction was not statistically significant. UPSIT performance declined ≥1.5 standard deviations in 5 controls and 7 patients. Change in UPSIT scores of patients correlated positively with volume change in the left putamen, right thalamus, and right caudate nucleus. Olfactory loss over time in PD and controls is similar, but we have observed significant correlation between this loss and basal ganglia volumes only in patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

    OpenAIRE

    Hensman Moss, Davina J; Pardinas, Antonio; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A

    2017-01-01

    Background\\ud \\ud Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.\\ud \\ud Methods\\ud \\ud We generated a progression score on the basis of principal ...

  20. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Chase, Gary; Lu, Mei

    2004-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  1. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Lu, Mei

    2006-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  2. Serum tryptase monitoring in indolent systemic mastocytosis: association with disease features and patient outcome.

    Directory of Open Access Journals (Sweden)

    Almudena Matito

    Full Text Available BACKGROUND: Serum baseline tryptase (sBT is a minor diagnostic criterion for systemic mastocytosis (SM of undetermined prognostic impact. We monitored sBT levels in indolent SM (ISM patients and investigated its utility for predicting disease behaviour and outcome. METHODS: In total 74 adult ISM patients who were followed for ≥48 months and received no cytoreductive therapy were retrospectively studied. Patients were classified according to the pattern of evolution of sBT observed. RESULTS: Overall 16/74 (22% cases had decreasing sBT levels, 48 (65% patients showed increasing sBT levels and 10 (13% patients showed a fluctuating pattern. Patients with significantly increasing sBT (sBT slope ≥0.15 after 48 months of follow-up showed a slightly greater rate of development of diffuse bone sclerosis (13% vs. 2% and hepatomegaly plus splenomegaly (16% vs. 5%, as well as a significantly greater frequency of multilineage vs. mast cells (MC-restricted KIT mutation (p = 0.01 together with a greater frequency of cases with progression of ISM to smouldering and aggressive SM (p = 0.03, and a shorter progression-free survival (p = 0.03. CONCLUSIONS: Monitoring of sBT in ISM patients is closely associated with poor prognosis disease features as well as with disease progression, pointing out the need for a closer follow-up in ISM patients with progressively increasing sBT values.

  3. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review.

    Science.gov (United States)

    Moreno, Juan Antonio; Yuste, Claudia; Gutiérrez, Eduardo; Sevillano, Ángel M; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Praga, Manuel; Egido, Jesús

    2016-04-01

    Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.

  4. Retrospective study of the effect of disease progression on patient reported outcomes in HER-2 negative metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Yu Elaine

    2011-06-01

    Full Text Available Abstract Background This retrospective study evaluated the impact of disease progression and of specific sites of metastasis on patient reported outcomes (PROs that assess symptom burden and health related quality of life (HRQoL in women with metastatic breast cancer (mBC. Methods HER-2 negative mBC patients (n = 102 were enrolled from 7 U.S. community oncology practices. Demographic, disease and treatment characteristics were abstracted from electronic medical records and linked to archived Patient Care Monitor (PCM assessments. The PCM is a self-report measure of symptom burden and HRQoL administered as part of routine care in participating practices. Linear mixed models were used to examine change in PCM scores over time. Results Mean age was 57 years, with 72% of patients Caucasian, and 25% African American. Median time from mBC diagnosis to first disease progression was 8.8 months. Metastasis to bone (60%, lung (28% and liver (26% predominated at initial metastatic diagnosis. Results showed that PCM items assessing fatigue, physical pain and trouble sleeping were sensitive to either general effects of disease progression or to effects associated with specific sites of metastasis. Progression of disease was also associated with modest but significant worsening of General Physical Symptoms, Treatment Side Effects, Acute Distress and Impaired Performance index scores. In addition, there were marked detrimental effects of liver metastasis on Treatment Side Effects, and of brain metastasis on Acute Distress. Conclusions Disease progression has a detrimental impact on cancer-related symptoms. Delaying disease progression may have a positive impact on patients' HRQoL.

  5. Timely Referral to Outpatient Nephrology Care Slows Progression and Reduces Treatment Costs of Chronic Kidney Diseases

    Directory of Open Access Journals (Sweden)

    Gerhard Lonnemann

    2017-03-01

    Discussion: Timely referral to outpatient nephrology care is associated with slowed disease progression, less hospital admissions, reduced total treatment costs, and improved survival in patients with CKD.

  6. Verbal monitoring in Parkinson’s disease: A comparison between internal and external monitoring

    Science.gov (United States)

    Mertens, Jolien; Mariën, Peter; Santens, Patrick; Pickut, Barbara A.; Hartsuiker, Robert J.

    2017-01-01

    Patients with Parkinson’s disease (PD) display a variety of impairments in motor and non-motor language processes; speech is decreased on motor aspects such as amplitude, prosody and speed and on linguistic aspects including grammar and fluency. Here we investigated whether verbal monitoring is impaired and what the relative contributions of the internal and external monitoring route are on verbal monitoring in patients with PD relative to controls. Furthermore, the data were used to investigate whether internal monitoring performance could be predicted by internal speech perception tasks, as perception based monitoring theories assume. Performance of 18 patients with Parkinson’s disease was measured on two cognitive performance tasks and a battery of 11 linguistic tasks, including tasks that measured performance on internal and external monitoring. Results were compared with those of 16 age-matched healthy controls. PD patients and controls generally performed similarly on the linguistic and monitoring measures. However, we observed qualitative differences in the effects of noise masking on monitoring and disfluencies and in the extent to which the linguistic tasks predicted monitoring behavior. We suggest that the patients differ from healthy subjects in their recruitment of monitoring channels. PMID:28832595

  7. Generalizability of the Disease State Index Prediction Model for Identifying Patients Progressing from Mild Cognitive Impairment to Alzheimer's Disease

    NARCIS (Netherlands)

    Hall, A.; Munoz-Ruiz, M.; Mattila, J.; Koikkalainen, J.; Tsolaki, M.; Mecocci, P.; Kloszewska, I.; Vellas, B.; Lovestone, S.; Visser, P.J.; Lotjonen, J.; Soininen, H.

    2015-01-01

    Background: The Disease State Index (DSI) prediction model measures the similarity of patient data to diagnosed stable and progressive mild cognitive impairment (MCI) cases to identify patients who are progressing to Alzheimer's disease. Objectives: We evaluated how well the DSI generalizes across

  8. Monitoring and diagnosis of Alzheimer's disease using noninvasive compressive sensing EEG

    Science.gov (United States)

    Morabito, F. C.; Labate, D.; Morabito, G.; Palamara, I.; Szu, H.

    2013-05-01

    The majority of elderly with Alzheimer's Disease (AD) receive care at home from caregivers. In contrast to standard tethered clinical settings, a wireless, real-time, body-area smartphone-based remote monitoring of electroencephalogram (EEG) can be extremely advantageous for home care of those patients. Such wearable tools pave the way to personalized medicine, for example giving the opportunity to control the progression of the disease and the effect of drugs. By applying Compressive Sensing (CS) techniques it is in principle possible to overcome the difficulty raised by smartphones spatial-temporal throughput rate bottleneck. Unfortunately, EEG and other physiological signals are often non-sparse. In this paper, it is instead shown that the EEG of AD patients becomes actually more compressible with the progression of the disease. EEG of Mild Cognitive Impaired (MCI) subjects is also showing clear tendency to enhanced compressibility. This feature favor the use of CS techniques and ultimately the use of telemonitoring with wearable sensors.

  9. Progression of autosomal dominant kidney disease: measurement of the stage transitions of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Christopher M Blanchette

    2015-04-01

    Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. Methods: This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000–2/28/2013 and ≥6 months of previous continuous enrollment (baseline within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. Results: ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. Conclusions: These results suggest that distribution of patients by age at transition

  10. Use of Acoustic Emission to Monitor Progressive Damage Accumulation in KEVLAR® 49 Composites

    Science.gov (United States)

    Waller, J. M.; Andrade, E.; Saulsberry, R. L.

    2010-02-01

    Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar® 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio <1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

  11. Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study.

    Science.gov (United States)

    Martínez-Payá, Jacinto J; Ríos-Díaz, José; Medina-Mirapeix, Francesc; Vázquez-Costa, Juan F; Del Baño-Aledo, María Elena

    2018-01-01

    The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  12. Use of Acoustic Emission to Monitor Progressive Damage Accumulation in Kevlar (R) 49 Composites

    Science.gov (United States)

    Waller, Jess M.; Saulsberry, Regor L.; Andrade, Eduardo

    2009-01-01

    Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar(Registeres TradeMark) 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

  13. Risk Matrix for Prediction of Disease Progression in a Referral Cohort of Patients with Crohn's Disease.

    Science.gov (United States)

    Lakatos, Peter L; Sipeki, Nora; Kovacs, Gyorgy; Palyu, Eszter; Norman, Gary L; Shums, Zakera; Golovics, Petra A; Lovasz, Barbara D; Antal-Szalmas, Peter; Papp, Maria

    2015-10-01

    Early identification of patients with Crohn's disease (CD) at risk of subsequent complications is essential for adapting the treatment strategy. We aimed to develop a prediction model including clinical and serological markers for assessing the probability of developing advanced disease in a prospective referral CD cohort. Two hundred and seventy-one consecutive CD patients (42.4% males, median follow-up 108 months) were included and followed up prospectively. Anti-Saccharomyces cerevisiae antibodies (ASCA IgA/IgG) were determined by enzyme-linked immunosorbent assay. The final analysis was limited to patients with inflammatory disease behaviour at diagnosis. The final definition of advanced disease outcome was having intestinal resection or disease behaviour progression. Antibody (ASCA IgA and/or IgG) status, disease location and need for early azathioprine were included in a 3-, 5- and 7-year prediction matrix. The probability of advanced disease after 5 years varied from 6.2 to 55% depending on the combination of predictors. Similar findings were obtained in Kaplan-Meier analysis; the combination of ASCA, location and early use of azathioprine was associated with the probability of developing advanced disease (p < 0.001, log rank test). Our prediction models identified substantial differences in the probability of developing advanced disease in the early disease course of CD. Markers identified in this referral cohort were different from those previously published in a population-based cohort, suggesting that different prediction models should be used in the referral setting. 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.

  14. [Wireless device for monitoring the patients with chronic disease].

    Science.gov (United States)

    Ciorap, R; Zaharia, D; Corciovă, C; Ungureanu, Monica; Lupu, R; Stan, A

    2008-01-01

    Remote monitoring of chronic diseases can improve health outcomes and potentially lower health care costs. The high number of the patients, suffering of chronically diseases, who wish to stay at home rather then in a hospital increasing the need of homecare monitoring and have lead to a high demand of wearable medical devices. Also, extended patient monitoring during normal activity has become a very important target. In this paper are presented the design of the wireless monitoring devices based on ultra low power circuits, high storage memory flash, bluetooth communication and the firmware for the management of the monitoring device. The monitoring device is built using an ultra low power microcontroller (MSP430 from Texas Instruments) that offers the advantage of high integration of some circuits. The custom made electronic boards used for biosignal acquisition are also included modules for storage device (SD/MMC card) with FAT32 file system and Bluetooth device for short-range communication used for data transmission between monitoring device and PC or PDA. The work was focused on design and implementation of an ultra low power wearable device able to acquire patient vital parameters, causing minimal discomfort and allowing high mobility. The proposed wireless device could be used as a warning system for monitoring during normal activity.

  15. Glaucoma Monitoring in a Clinical Setting Glaucoma Progression Analysis vs Nonparametric Progression Analysis in the Groningen Longitudinal Glaucoma Study

    NARCIS (Netherlands)

    Wesselink, Christiaan; Heeg, Govert P.; Jansonius, Nomdo M.

    Objective: To compare prospectively 2 perimetric progression detection algorithms for glaucoma, the Early Manifest Glaucoma Trial algorithm (glaucoma progression analysis [GPA]) and a nonparametric algorithm applied to the mean deviation (MD) (nonparametric progression analysis [NPA]). Methods:

  16. Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Masataka Kikuchi

    Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs, we identified the PINs expressed in three brain regions: the entorhinal cortex (EC, hippocampus (HIP and superior frontal gyrus (SFG. Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system.

  17. Mass Spectrometric Methodologies for Investigating the Metabolic Signatures of Parkinson's Disease: Current Progress and Future Perspectives.

    Science.gov (United States)

    Gill, Emily L; Koelmel, Jeremy P; Yost, Richard A; Okun, Michael S; Vedam-Mai, Vinata; Garrett, Timothy J

    2018-03-06

    Parkinson's disease (PD) is a neurodegenerative disorder resulting from the loss of dopaminergic neurons of the substantia nigra as well as degeneration of motor and nonmotor basal ganglia circuitries. Typically known for classical motor deficits (tremor, rigidity, bradykinesia), early stages of the disease are associated with a large nonmotor component (depression, anxiety, apathy, etc.). Currently, there are no definitive biomarkers of PD, and the measurement of dopamine metabolites does not allow for detection of prodromal PD nor does it aid in long-term monitoring of disease progression. Given that PD is increasingly recognized as complex and heterogeneous, involving several neurotransmitters and proteins, it is of importance that we advance interdisciplinary studies to further our knowledge of the molecular and cellular pathways that are affected in PD. This approach will possibly yield useful biomarkers for early diagnosis and may assist in the development of disease-modifying therapies. Here, we discuss preanalytical factors associated with metabolomics studies, summarize current mass spectrometric methodologies used to evaluate the metabolic signature of PD, and provide future perspectives of the rapidly developing field of MS in the context of PD.

  18. Early energy deficit in Huntington disease: identification of a plasma biomarker traceable during disease progression.

    Directory of Open Access Journals (Sweden)

    Fanny Mochel

    Full Text Available Huntington disease (HD is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1H NMR spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA, valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide.

  19. Idaho Habitat/Natural Production Monitoring, Pt. I: General Monitoring Subproject : Annual Progress Report 1990.

    Energy Technology Data Exchange (ETDEWEB)

    Rich, Bruce A.; Scully, Richard J.; Petrosky, Charles Edward

    1992-01-01

    The Idaho Department of Fish and Game (IDFG) has been monitoring and evaluating proposed and existing habitat improvement projects for rainbow-steelhead trout Oncorhynchus mykiss, hereafter called steelhead, and chinook salmon O. tshawytscha, hereafter called chinook, in the Clearwater and Salmon River drainages for the past seven years. Projects included in the evaluation are funded by, or proposed for funding by, the Bonneville Power Administration (BPA) under the Northwest Power Planning Act as off-site mitigation for downstream hydropower development on the Snake and Columbia rivers. This evaluation project is also funded under the same authority (Fish and Wildlife Program, Northwest Power Planning Council). A mitigation record is being developed using increased carrying capacity and/or survival as the best measure of benefit from a habitat enhancement project. Determination of full benefit from a project depends on completion or maturation of the project and presence of adequate numbers of fish to document actual increases in fish production. The depressed status of upriver anadromous stocks has precluded measuring full benefits of any habitat project in Idaho. Partial benefit is credited to the mitigation record in the interim period of run restoration.

  20. Self-Calibrating Ultrasonic Methods for In-Situ Monitoring of Fatigue Crack Progression

    International Nuclear Information System (INIS)

    Michaels, J.E.; Mi, B.; Cobb, A.C.; Michaels, T.E.; Stobbe, D.M.

    2005-01-01

    Ultrasonic sensors permanently affixed to aluminum coupons are used to monitor progression of damage during fatigue testing with the long term goal of structural health monitoring for diagnostics and prognostics. Necessary for success are proper design of the ultrasonic testing methods, robust transducer mounting techniques, and real-time signal processing for determining the state of the structure. It is also highly desirable for the overall system to be self-calibrating with built-in diagnostics in order to detect and compensate for sensor degradation or failure. Self-calibrating ultrasonic techniques are applied for monitoring of cracks initiating and propagating from the inaccessible inner diameters of rivet holes where the transducers are mounted on the accessible specimen surface. Angle beam ultrasonic methods are utilized that are suitable for detecting small defects in critical local regions of high stress. Results are presented for aluminum coupons subjected to low cycle fatigue and demonstrate ultrasonic tracking of crack growth

  1. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease

    DEFF Research Database (Denmark)

    Currie, Gemma; Taylor, Alison H M; Fujita, Toshiro

    2016-01-01

    BACKGROUND: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemi...... pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit....

  2. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease.

    Science.gov (United States)

    Lindner, Moritz; Lambertus, Stanley; Mauschitz, Matthias M; Bax, Nathalie M; Kersten, Eveline; Lüning, Anna; Nadal, Jennifer; Schmitz-Valckenberg, Steffen; Schmid, Matthias; Holz, Frank G; Hoyng, Carel B; Fleckenstein, Monika

    2017-02-01

    To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbull's estimator. A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

  3. Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring

    Directory of Open Access Journals (Sweden)

    Hoffmann Björn

    2009-10-01

    Full Text Available Abstract Background In Fabry disease (α-galactosidase A deficiency accumulation of Globotriaosylceramide (Gb3 leads to progressive organ failure and premature death. The introduction of enzyme replacement therapy (ERT was the beginning of a new era in this disorder, and has prompted a broad range of research activities. This review aims to summarize recent developments and progress with high impact for Fabry disease. Methods A Pubmed analysis was performed using the search terms "Fabry disease", "Anderson-Fabry disease", "alpha-galactosidase A" and "Gb3". Of the given publications by 31st January 2009 only original articles recently published in peer reviewed journals were included for this review. Case reports were included only when they comprised a new aspect. In addition we included relevant conference abstracts when the results had not already been published as original articles. Results Apart from Gb3-accumulation cellular and organ specific damages may be related also to inflammatory and immunological consequences. It will be interesting whether this may lead to new therapeutic strategies in the treatment of Fabry disease. Since newborn screening is still difficult in Fabry disease, detection of patients in populations at risk is of great importance. Undiagnosed patients with Fabry disease may still be found in cohorts of subjects with renal diseases, cardiomyopathy and TIA or stroke. Efforts should be undertaken to identify these individuals and initialise ERT in order to hault disease progression. It has also been demonstrated that Gb3-accumulation leads to pre-clinical damages and it is believed that early treatment may be the only possibility so far to prevent irreversible organ damage.

  4. Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women

    NARCIS (Netherlands)

    Jarrin, Inmaculada; Geskus, Ronald; Bhaskaran, Krishnan; Prins, Maria; Perez-Hoyos, Santiago; Muga, Roberto; Hernández-Aguado, Ildefonso; Meyer, Laurence; Porter, Kholoud; del Amo, Julia; Bucher, Heiner; Chêne, Geneviève; Pillay, Deenan; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Walker, Sarah; Babiker, Abdel; Darbyshire, Janet; de Luca, Andrea; Fisher, Martin; Goujard, Cécile; Kaldor, John; Kelleher, Tony; Gelgor, Linda; Ramacciotti, Tim; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Pedersen, Court; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Vanhems, Philippe; Boufassa, Faroudy; Hamouda, Osamah; Kucherer, Claudia; Pantazis, Nikos; Hatzakis, Angelos; Paraskevis, Dimitrios; Karafoulidou, Anastasia; Rezza, Giovanni; Dorrucci, Maria; Longo, Benedetta; Balotta, Claudia; Coutinho, Roel

    2008-01-01

    To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada

  5. Role of rasagiline in treating Parkinson’s disease: effect on disease progression

    Directory of Open Access Journals (Sweden)

    Irene A Malaty

    2009-05-01

    Full Text Available Irene A Malaty, Hubert H FernandezUniversity of Florida Movement Disorders Center, Gainesville, FL, USAAbstract: Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson’s disease (PD patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson’s Disease Outpatients, and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson’s Rasagiline: Efficacy and Safety in the Treatment of “Off”, and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily. Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration.Keywords: rasagiline, Parkinson’s disease, neuroprotection, selegiline

  6. Laboratory studies and Pompe disease: from suspicion to therapy monitoring

    Directory of Open Access Journals (Sweden)

    K. V. Savost’yanov

    2016-01-01

    Full Text Available Pompe disease (PD is a rare, progressive, commonly fatal inherited autosomal recessive disease that is difficult to diagnose due to its obvious clinical heterogeneity and low awareness among physicians. Access to the laboratory diagnosis of rare diseases increases every year. In the past several years, Russian and foreign laboratories have achieved considerable success in accelerating and improving the diagnostic accuracy of PD. Unfortunately, the Russian-language literature contains scarce relevant information on the laboratory diagnosis of PD. This review is to fill up this gap. 

  7. Screening protocols to monitor respiratory status in primary immunodeficiency disease : Findings from a European survey and subclinical infection working group

    NARCIS (Netherlands)

    Jolles, S.; Sánchez-Ramón, S.; Quinti, I.; Soler-Palacín, P.; Agostini, C.; Florkin, B.; Couderc, L.J.; Brodszki, N.; Jones, A.; Longhurst, H.; Warnatz, K.; Haerynck, F.; Matucci, A.; de Vries, E.

    2017-01-01

    Many patients with primary immunodeficiency (PID) who have antibody deficiency develop progressive lung disease due to underlying subclinical infection and inflammation. To understand how these patients are monitored we conducted a retrospective survey based on patient records of 13 PID centres

  8. Available data sources for monitoring non-communicable diseases and their risk factors in South Africa

    Directory of Open Access Journals (Sweden)

    M Wandai

    2017-04-01

    Full Text Available Background. Health information systems for monitoring chronic non-communicable diseases (NCDs in South Africa (SA are relatively less advanced than those for infectious diseases (particularly tuberculosis and HIV and for maternal and child health. NCDs are now the largest cause of premature mortality owing to exposure to risk factors arising from obesity that include physical inactivity and accessible, cheap but unhealthy diets. The National Strategic Plan for the Prevention and Control of Non-Communicable Diseases 2013 - 17 developed by the SA National Department of Health outlines targets and monitoring priorities. Objectives. To assess data sources relevant for monitoring NCDs and their risk factors by identifying the strengths and weaknesses, including usability and availability, of surveys and routine systems focusing at national and certain sub-national levels. Methods. Publicly available survey and routine data sources were assessed for variables collected, their characteristics, frequency of data collection, geographical coverage and data availability. Results. Survey data sources were found to be quite different in the way data variables are collected, their geographical coverage and also availability, while the main weakness of routine data sources was poor quality of data. Conclusions. To provide a sound basis for monitoring progress of NCDs and related risk factors, we recommend harmonising and strengthening available SA data sources in terms of data quality, definitions, categories used, timeliness, disease coverage and biomarker measurement.

  9. The applause sign and neuropsychological profile in progressive supranuclear palsy and Parkinson's disease.

    Science.gov (United States)

    Somme, Johanne; Gómez-Esteban, Juan Carlos; Tijero, Beatriz; Berganzo, Koldo; Lezcano, Elena; Zarranz, Juan Jose

    2013-08-01

    The applause sign has been associated with various neurodegenerative diseases. We investigate its validity in the differential diagnosis of progressive supranuclear palsy and Parkinson's disease, and its relationship with neuropsychological tests. 23 patients with progressive supranuclear palsy and 106 patients with Parkinson's disease were included and administered the following scales: progressive supranuclear palsy rating scale, unified Parkinson's disease rating scale (UPDRS), mini-mental state examination (MMSE), frontal assessment battery (FAB), neuropsychiatric inventory and three-clap test. 73.9% with progressive supranuclear palsy and 21.7% with Parkinson's disease showed a positive applause sign. Only a positive applause sign, UPDRS II score and disease duration were found to be predictors of progressive supranuclear palsy. Both patient-groups showed statistically significant correlations between the applause sign and neuropsychological tests: in progressive supranuclear palsy patients MMSE correlation coefficient: 0.62 (p: 0.002) and FAB correlation coefficient: 0.48 (p: 0.02), and in Parkinson's disease patients MMSE correlation coefficient: 0.47 (pspecific to progressive supranuclear palsy and may also be observed in Parkinson's disease patients with altered cognition, and it's related to cortical frontal abnormalities such as language disorders and inhibitory control. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Anosognosia in Alzheimer disease: Prevalence, associated factors, and influence on disease progression.

    Science.gov (United States)

    Castrillo Sanz, A; Andrés Calvo, M; Repiso Gento, I; Izquierdo Delgado, E; Gutierrez Ríos, R; Rodríguez Herrero, R; Rodríguez Sanz, F; Tola-Arribas, M A

    2016-06-01

    Anosognosia is a frequent symptom in Alzheimer disease (AD). The objective of this article is to describe prevalence of this condition at time of diagnosis and analyse any predisposing factors and their influence on disease progression. Observational, prospective, and analytical multi-centre study in an outpatient setting. Patients recently diagnosed with AD (NINCDS-ADRDA criteria) were included. Each patient underwent two cognitive, functional, and neuropsychiatric assessments separated by an interval of 18 months. The Clinical Insight Rating Scale was employed as a measure of anosognosia (CIR, scored 0-8). Progression was defined as an increase in the Clinical Dementia Rating Scale-sum of boxes of more than 2.5 points. The predictor variables were analysed using binary logistic regression. The study included 127 patients, and 94 completed both assessments. Of the total, 31.5% displayed severe anosognosia (CIR 7-8); 39.4%, altered level of consciousness (CIR 3-6); and 29.1%, normal awareness (CIR 0-2). The median baseline CIR in this cohort was 4 (Q1-Q3: 1-7), and at 18 months, 6 (Q1-Q3: 3-8), Pde Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and progressive diseases of the central nervous system.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1997-01-01

    A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and

  12. Role of rasagiline in treating Parkinson's disease: Effect on disease progression.

    Science.gov (United States)

    Malaty, Irene A; Fernandez, Hubert H

    2009-08-01

    Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson's disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients), and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off", and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily). Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily) and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration.

  13. Role of rasagiline in treating Parkinson’s disease: Effect on disease progression

    Science.gov (United States)

    Malaty, Irene A; Fernandez, Hubert H

    2009-01-01

    Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson’s disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson’s Disease Outpatients), and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson’s Rasagiline: Efficacy and Safety in the Treatment of “Off”, and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily). Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily) and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration. PMID:19753135

  14. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?

    LENUS (Irish Health Repository)

    Lonergan, Roisin

    2012-02-01

    Disease-modifying therapy is ineffective in disabled patients (Expanded Disability Status Scale [EDSS] > 6.5) with secondary progressive multiple sclerosis (MS) without relapses, or in primary progressive MS. Many patients with secondary progressive MS who initially had relapsing MS continue to use disease-modifying therapies. The enormous associated costs are a burden to health services. Regular assessment is recommended to guide discontinuation of disease-modifying therapies when no longer beneficial, but this is unavailable to many patients, particularly in rural areas. The objectives of this study are as follows: 1. To observe use of disease-modifying therapies in patients with progressive multiple sclerosis and EDSS > 6.5. 2. To examine approaches used by a group of international MS experts to stopping-disease modifying therapies in patients with secondary progressive MS without relapses. During an epidemiological study in three regions of Ireland (southeast Dublin city, and Wexford and Donegal Counties), we recorded details of disease-modifying therapies in patients with progressive MS and EDSS > 6.5. An e-questionnaire was sent to 26 neurologists with expert knowledge of MS, asking them to share their approach to stopping disease-modifying therapies in patients with secondary progressive MS. Three hundred and thirty-six patients were studied: 88 from southeast Dublin, 99 from Wexford and 149 from Donegal. Forty-four had EDSS > 6.5: 12 were still using disease-modifying therapies. Of the surveyed neurologists, 15 made efforts to stop disease-modifying therapies in progressive multiple sclerosis, but most did not insist. A significant proportion (12 of 44 patients with progressive MS and EDSS > 6.5) was considered to be receiving therapy without benefit. Eleven of the 12 were from rural counties, reflecting poorer access to neurology services. The costs of disease-modifying therapies in this group (>170,000 euro yearly) could be re-directed towards development

  15. Dynamic generalized linear models for monitoring endemic diseases

    DEFF Research Database (Denmark)

    Lopes Antunes, Ana Carolina; Jensen, Dan; Hisham Beshara Halasa, Tariq

    2016-01-01

    The objective was to use a Dynamic Generalized Linear Model (DGLM) based on abinomial distribution with a linear trend, for monitoring the PRRS (Porcine Reproductive and Respiratory Syndrome sero-prevalence in Danish swine herds. The DGLM was described and its performance for monitoring control...... and eradication programmes based on changes in PRRS sero-prevalence was explored. Results showed a declining trend in PRRS sero-prevalence between 2007 and 2014 suggesting that Danish herds are slowly eradicating PRRS. The simulation study demonstrated the flexibility of DGLMs in adapting to changes intrends...... in sero-prevalence. Based on this, it was possible to detect variations in the growth model component. This study is a proof-of-concept, demonstrating the use of DGLMs for monitoring endemic diseases. In addition, the principles stated might be useful in general research on monitoring and surveillance...

  16. Application of Addenbrooke's cognitive examination to diagnosis and monitoring of progressive primary aphasia.

    Science.gov (United States)

    Leyton, Cristian E; Hornberger, Michael; Mioshi, Eneida; Hodges, John R

    2010-01-01

    Primary progressive aphasia (PPA) comprises 2 main variants: semantic dementia (SD) and progressive nonfluent aphasia (PNFA). Addenbrooke's Cognitive Examination (ACE) has become widely used for the diagnosis of dementias. Less information, however, is available about its ability to detect and monitor changes in cognition in PPA. We aimed to analyse the sensitivity and longitudinal changes of ACE scores in 2 subforms of PPA. We included 63 SD and 45 PNFA cases, all of whom had at least 2 assessments. Sensitivity levels, annualised rates of change and difference in scores over time on repeated ACE measurements were calculated. A cut-off of 88 points detected 95% of the PNFA and SD cases. Longitudinal analysis showed an average annual decline of 10 points per year, with no significant difference between groups. The ACE is a useful tool for detecting and tracking the evolution of PPA. Copyright 2010 S. Karger AG, Basel.

  17. A Framework for (Tele-) Monitoring of the Rehabilitation Progress in Stroke Patients

    Science.gov (United States)

    David, V.; Haller, M.; Kotzian, S.; Hofmann, M.; Schlossarek, S.; Eichholzer, K.; Winkler, M.; Frohner, M.; Reichel, M.; Mayr, W.; Rafolt, D.

    2015-01-01

    Background Preservation of mobility in conjunction with an independent life style is one of the major goals of rehabilitation after stroke. Objectives The Rehab@Home framework shall support the continuation of rehabilitation at home. Methods The framework consists of instrumented insoles, connected wirelessly to a 3G ready tablet PC, a server, and a web-interface for medical experts. The rehabilitation progress is estimated via automated analysis of movement data from standardized assessment tests which are designed according to the needs of stroke patients and executed via the tablet PC application. Results The Rehab@Home framework’s implementation is finished and ready for the field trial (at five patients’ homes). Initial testing of the automated evaluation of the standardized mobility tests shows reproducible results. Conclusions Therefore it is assumed that the Rehab@Home framework is applicable as monitoring tool for the gait rehabilitation progress in stroke patients. PMID:26767068

  18. Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression.

    Science.gov (United States)

    Green, Colin; Shearer, James; Ritchie, Craig W; Zajicek, John P

    2011-01-01

    To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD. A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review. The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD. Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  19. Study progress on free radicals and graves disease

    International Nuclear Information System (INIS)

    Zhang Ruiguo; Jin Jianhua

    2009-01-01

    Free radical-mediated oxidative injury has been closely implicated in the occurrence and development of many diseases. Graves disease was also accompanied by changes of the free radicals, especially for reactive oxygen species and reactive nitrogen, et al, and the oxidative stress can cause a certain degree of injury on the thyroid and other human important organs. Antithyroid drug and 131 I treatment of Graves disease, the oxidative and antioxidative parameters can also be changed. (authors)

  20. Progression and prognostic indicators of bronchial disease in children with sickle cell disease.

    Science.gov (United States)

    Williams, Sophia N; Nussbaum, Eliezer; Yoonessi, Leila; Morphew, Tricia; Randhawa, Inderpal

    2014-06-01

    The pulmonary complications of sickle cell disease (SCD) are a leading cause of morbidity and mortality (MacLean et al. Am J Respir Crit Care Med 178:1055-1059, 2008; Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; National Heart, Lung, and Blood Institute, 2009). Despite this recognition, predictive markers of lung dysfunction progression remain elusive (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Platt et al. N Engl J Med 330:1639-1644, 1994; Caboot et al. Curr Opin Pediatr 20:279-287, 2008; Field et al. Am J Hematol 83:574-576, 2008; Shirlo et al. Peadiatr Respir Review 12:78-82, 2011). This study was designed describe the longitudinal progression and identify specific markers that influence bronchial disease in SCD. A retrospective, chart review of 89 patients with SCD was conducted. All patients underwent spirometry in conjunction with body plethysmography as part of routine care. Eleven lung function variables were assessed, five of which were selected to establish patterns of normal, obstructive, restrictive, or mixed obstructive-restrictive physiology (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Field et al. Am J Hematol 83:574-576, 2008). In the unadjusted model, forced expiratory volume in one second (FEV1)% of predicted trended downward with age, while total lung capacity (TLC)% of predicted showed a bimodal distribution and carbon monoxide diffusion capacity corrected for hemoglobin (DLCOcor)% of predicted remained stable. Adjusting for acute chest syndrome (ACS) episodes, medication status, and growth velocity (GV), the final model demonstrated that the downward trend between FEV1% of predicted with age was further influenced by the latter two factors. Initial decline in FEV1% of predicted is associated with worsening pulmonary dysfunction over time. Independent of ACS episodes, the factors most influential on the progression of FEV1% predicted include the introduction of medications as well as the

  1. Ground-water monitoring compliance projects for Hanford Site facilities: Annual progress report for 1987

    International Nuclear Information System (INIS)

    Hall, S.H.

    1988-09-01

    This report describes progress during 1987 of five Hanford Site ground water monitoring projects. Four of these projects are being conducted according to regulations based on the federal Resource Conservation and Recovery Act of 1976 and the state Hazardous Waste Management Act. The fifth project is being conducted according to regulations based on the state Solid Waste Management Act. The five projects discussed herein are: 300 Area Process Trenches; 183-H Solar Evaporation Basins; 200 Areas Low-Level Burial Grounds; Nonradioactive Dangerous Waste Landfill; Solid Waste Landfill. For each of the projects, there are included, as applicable, discussions of monitoring well installations, water-table measurements, background and/or downgradient water quality and results of chemical analysis, and extent and rate of movement of contaminant plumes. 14 refs., 30 figs., 13 tabs

  2. Early Prediction of Disease Progression in Small Cell Lung Cancer: Toward Model-Based Personalized Medicine in Oncology.

    Science.gov (United States)

    Buil-Bruna, Núria; Sahota, Tarjinder; López-Picazo, José-María; Moreno-Jiménez, Marta; Martín-Algarra, Salvador; Ribba, Benjamin; Trocóniz, Iñaki F

    2015-06-15

    Predictive biomarkers can play a key role in individualized disease monitoring. Unfortunately, the use of biomarkers in clinical settings has thus far been limited. We have previously shown that mechanism-based pharmacokinetic/pharmacodynamic modeling enables integration of nonvalidated biomarker data to provide predictive model-based biomarkers for response classification. The biomarker model we developed incorporates an underlying latent variable (disease) representing (unobserved) tumor size dynamics, which is assumed to drive biomarker production and to be influenced by exposure to treatment. Here, we show that by integrating CT scan data, the population model can be expanded to include patient outcome. Moreover, we show that in conjunction with routine medical monitoring data, the population model can support accurate individual predictions of outcome. Our combined model predicts that a change in disease of 29.2% (relative standard error 20%) between two consecutive CT scans (i.e., 6-8 weeks) gives a probability of disease progression of 50%. We apply this framework to an external dataset containing biomarker data from 22 small cell lung cancer patients (four patients progressing during follow-up). Using only data up until the end of treatment (a total of 137 lactate dehydrogenase and 77 neuron-specific enolase observations), the statistical framework prospectively identified 75% of the individuals as having a predictable outcome in follow-up visits. This included two of the four patients who eventually progressed. In all identified individuals, the model-predicted outcomes matched the observed outcomes. This framework allows at risk patients to be identified early and therapeutic intervention/monitoring to be adjusted individually, which may improve overall patient survival. ©2015 American Association for Cancer Research.

  3. Impairment of vowel articulation as a possible marker of disease progression in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Sabine Skodda

    Full Text Available PURPOSE: The aim of the current study was to survey if vowel articulation in speakers with Parkinson's disease (PD shows specific changes in the course of the disease. METHOD: 67 patients with PD (42 male and 40 healthy speakers (20 male were tested and retested after an average time interval of 34 months. Participants had to read a given text as source for subsequent calculation of the triangular vowel space area (tVSA and vowel articulation index (VAI. Measurement of tVSA and VAI were based upon analysis of the first and second formant of the vowels /α/, /i/and /u/ extracted from defined words within the text. RESULTS: At first visit, VAI values were reduced in male and female PD patients as compared to the control group, and showed a further decrease at the second visit. Only in female Parkinsonian speakers, VAI was correlated to overall speech impairment based upon perceptual impression. VAI and tVSA were correlated to gait impairment, but no correlations were seen between VAI and global motor impairment or overall disease duration. tVSA showed a similar reduction in the PD as compared to the control group and was also found to further decline between first and second examination in female, but not in male speakers with PD. CONCLUSIONS: Measurement of VAI seems to be superior to tVSA in the description of impaired vowel articulation and its further decline in the course of the disease in PD. Since impairment of vowel articulation was found to be independent from global motor function but correlated to gait dysfunction, measurement of vowel articulation might have a potential to serve as a marker of axial disease progression.

  4. Development of a Conceptual Model of Disease Progression for Use in Economic Modeling of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Tabberer, Maggie; Gonzalez-McQuire, Sebastian; Muellerova, Hana; Briggs, Andrew H; Rutten-van Mölken, Maureen P M H; Chambers, Mike; Lomas, David A

    2017-05-01

    To develop and validate a new conceptual model (CM) of chronic obstructive pulmonary disease (COPD) for use in disease progression and economic modeling. The CM identifies and describes qualitative associations between disease attributes, progression and outcomes. A literature review was performed to identify any published CMs or literature reporting the impact and association of COPD disease attributes with outcomes. After critical analysis of the literature, a Steering Group of experts from the disciplines of health economics, epidemiology and clinical medicine was convened to develop a draft CM, which was refined using a Delphi process. The refined CM was validated by testing for associations between attributes using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). Disease progression attributes included in the final CM were history and occurrence of exacerbations, lung function, exercise capacity, signs and symptoms (cough, sputum, dyspnea), cardiovascular disease comorbidities, 'other' comorbidities (including depression), body composition (body mass index), fibrinogen as a biomarker, smoking and demographic characteristics (age, gender). Mortality and health-related quality of life were determined to be the most relevant final outcome measures for this model, intended to be the foundation of an economic model of COPD. The CM is being used as the foundation for developing a new COPD model of disease progression and to provide a framework for the analysis of patient-level data. The CM is available as a reference for the implementation of further disease progression and economic models.

  5. Monitoring emerging diseases of fish and shellfish using electronic sources.

    Science.gov (United States)

    Thrush, M A; Dunn, P L; Peeler, E J

    2012-10-01

    New and emerging fish and shellfish diseases represent an important constraint to the growth and sustainability of many aquaculture sectors and have also caused substantial economic and environmental impacts in wild stocks. This paper details the results of 8 years of a monitoring programme for emerging aquatic animal diseases reported around the world. The objectives were to track global occurrences and, more specifically, to identify and provide advanced warning of disease threats that may affect wild and farmed fish stocks in the UK. A range of electronic information sources, including Internet newsletters, alerting services and news agency releases, was systematically searched for reports of new diseases, new presentations of known pathogens and known diseases occurring in new geographic locations or new host species. A database was established to log the details of key findings, and 250 emerging disease events in 52 countries were recorded during the period of study. These included 14 new diseases and a further 16 known diseases in new species. Viruses and parasites accounted for the majority of reports (55% and 24%, respectively), and known diseases occurring in new locations were the most important emerging disease category (in which viruses were dominant). Emerging diseases were reported disproportionally in salmonid species (33%), in farmed populations (62%) and in Europe and North America (80%). The lack of reports from some regions with significant aquaculture or fishery production may indicate that emerging diseases are not being recognized in these areas owing to insufficient surveillance or testing or that these events are being under-reported. The results are discussed in relation to processes underpinning disease emergence in the aquatic environment. © 2011 Crown Copyright. Reproduced with the permission of the Controller of Her Majesty’s Stationery Office and Centre for Environment Fisheries & Aquaculture Science.

  6. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

    OpenAIRE

    de la Monte, Suzanne M.

    2012-01-01

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

  7. Is the Autism Treatment Evaluation Checklist a Useful Tool for Monitoring Progress in Children with Autism Spectrum Disorders?

    Science.gov (United States)

    Magiati, I.; Moss, J.; Yates, R.; Charman, T.; Howlin, P.

    2011-01-01

    Background: There are few well validated brief measures that can be used to assess the general progress of young children with autism spectrum disorders (ASD) over time. In the present study, the Autism Treatment Evaluation Checklist (ATEC) was used as part of a comprehensive assessment battery to monitor the progress of 22 school-aged children…

  8. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Meliana Riwanto

    Full Text Available Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD. Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect" plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+, a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1 in cystic kidneys of Cy/+ rats compared with wild-type (+/+ rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day for 5 weeks resulted in significantly lower kidney weights (-27% and 2-kidney/total-body-weight ratios (-20% and decreased renal cyst index (-48% compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min, BUN (0.69±0.26 vs 0.40±0.10 ml/min and uric acid (0.38±0.20 vs 0.21±0.10 ml/min, and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD.

  9. Dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease.

    Directory of Open Access Journals (Sweden)

    Yumiko Nakagawa-Toyama

    Full Text Available BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/h called 'HypoE' when fed an atherogenic, 'Paigen' diet develop occlusive, atherosclerotic coronary arterial disease (CHD, myocardial infarctions (MI, and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet. Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. METHODOLOGY/PRINCIPAL FINDINGS: HypoE mice were maintained on a standard lab chow diet (control until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. CONCLUSIONS/SIGNIFICANCE: HypoE mice provide a powerful, surgery-free, diet-'titratable' small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation on a variety of features of

  10. Progress of radionuclide diagnostic methods in central nervous system diseases

    International Nuclear Information System (INIS)

    Badmaev, K.N.; Zen'kovich, S.G.

    1982-01-01

    A summarry on modern radionuclide diagnosis achivements of central nervous system diseases is presented. Most optimal tumorotropic preparations and compounds in the view of decreasing irradiation does and optimazing image are given

  11. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression.

    Science.gov (United States)

    Estrada, Marta F; Rebelo, Sofia P; Davies, Emma J; Pinto, Marta T; Pereira, Hugo; Santo, Vítor E; Smalley, Matthew J; Barry, Simon T; Gualda, Emilio J; Alves, Paula M; Anderson, Elizabeth; Brito, Catarina

    2016-02-01

    3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Joint inversion of geophysical data for site characterization and restoration monitoring. 1998 annual progress report

    International Nuclear Information System (INIS)

    Berge, P.A.; Berryman, J.G.; Roberts, J.J.; Wildenschild, D.

    1998-01-01

    'The purpose of this project is to develop a computer code for joint inversion of seismic and electrical data, to improve underground imaging for site characterization and remediation monitoring. The computer code developed in this project will invert geophysical data to obtain direct estimates of porosity and saturation underground, rather than inverting for seismic velocity and electrical resistivity or other geophysical properties. This is intended to be a significant improvement in the state-of-the-art of underground imaging, since interpretation of data collected at a contaminated site would become much less subjective. Potential users include DOE scientists and engineers responsible for characterizing contaminated sites and monitoring remediation of contaminated sites. In this three-year project, the authors use a multi-phase approach consisting of theoretical and numerical code development, laboratory investigations, testing on available laboratory and borehole geophysics data sets, and a controlled field experiment, to develop practical tools for joint electrical and seismic data interpretation. This report summarizes work after about 1.7 years of a 3-year project. Progress on laboratory measurements is described first, followed by progress on developing algorithms for the inversion code to relate geophysical data to porosity and saturation.'

  13. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  14. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis

    NARCIS (Netherlands)

    Currie, G. (Gemma); Taylor, A.H.M. (Alison H. M.); Fujita, T. (Toshiro); Ohtsu, H. (Hiroshi); Lindhardt, M. (Morten); K. Rossing; Boesby, L. (Lene); Edwards, N.C. (Nicola C.); Ferro, C.J. (Charles J.); J. Townend (Jonathan); A.H. van den Meiracker (Anton); Saklayen, M.G. (Mohammad G.); Oveisi, S. (Sonia); Jardine, A.G. (Alan G.); C. Delles (Christian); Preiss, D.J. (David J.); Mark, P.B. (Patrick B.)

    2016-01-01

    textabstractBackground: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease.

  15. Teacher Progress Monitoring of Instructional and Behavioral Management Practices: An Evidence-Based Approach to Improving Classroom Practices

    Science.gov (United States)

    Reddy, Linda A.; Dudek, Christopher M.

    2014-01-01

    In the era of teacher evaluation and effectiveness, assessment tools that identify and monitor educators' instruction and behavioral management practices are in high demand. The Classroom Strategies Scale (CSS) Observer Form is a multidimensional teacher progress monitoring tool designed to assess teachers' usage of instructional and behavioral…

  16. Diminished disease progression rate in a chronic kidney disease population following the replacement of dietary water source with quality drinking water: A pilot study.

    Science.gov (United States)

    Siriwardhana, Edirisinghe Arachchige Ranga Iroshanie Edirisinghe; Perera, Ponnamperuma Aratchige Jayasumana; Sivakanesan, Ramiah; Abeysekara, Tilak; Nugegoda, Danaseela Bandara; Weerakoon, Kosala; Siriwardhana, Dunusingha Asitha Surandika

    2018-05-01

    Environmental toxin/s is alleged to be the contributory factor for the chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka. The potential of drinking water as a medium for the nephrotoxic agents in the affected subjects has been comprehensively discoursed in the recent past. The present study was aimed to assess the effect of replacing the habitual drinking water on the kidney function of CKDu patients residing in the North Central Province of Sri Lanka: METHODS: An interventional study was carried out to assess the disease progression rate of a CKDu population whose habitual drinking water was replaced by bottled spring water certified by Sri Lanka Standard (SLS) for a period of 18 month along with a population of CKDu patients who continued with their usual drinking water. Kidney function of subjects in both groups were monitored in terms of blood pressure, serum creatinine, serum calcium, serum phosphorus, hemoglobin, estimated glomerular filtration rate and urinary protein at 6 months intervals during the intervention and follow up periods. Diminished disease progression rate was observed in CKDu patients in the intervention group when compared with the non- intervention group based on serum creatinine, Hb, estimated glomerular filtration rate and urinary protein levels. Extensive interventional studies are required to generalize effect of drinking water on CKDu population. The habitual drinking water is likely to be a contributory factor towards the progression of the disease. © 2017 Asian Pacific Society of Nephrology.

  17. Lipidomic Signature of Progression of Chronic Kidney Disease in the Chronic Renal Insufficiency Cohort

    Directory of Open Access Journals (Sweden)

    Farsad Afshinnia

    2016-11-01

    Discussion: We conclude that a distinct panel of lipids may improve prediction of progression of chronic kidney disease beyond estimated glomerular filtration rate and urine protein-to-creatinine ratio when added to the base model.

  18. Mobile Monitoring and Reasoning Methods to Prevent Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Diego López-de-Ipiña

    2013-05-01

    Full Text Available With the recent technological advances, it is possible to monitor vital signs using Bluetooth-enabled biometric mobile devices such as smartphones, tablets or electric wristbands. In this manuscript, we present a system to estimate the risk of cardiovascular diseases in Ambient Assisted Living environments. Cardiovascular disease risk is obtained from the monitoring of the blood pressure by means of mobile devices in combination with other clinical factors, and applying reasoning techniques based on the Systematic Coronary Risk Evaluation Project charts. We have developed an end-to-end software application for patients and physicians and a rule-based reasoning engine. We have also proposed a conceptual module to integrate recommendations to patients in their daily activities based on information proactively inferred through reasoning techniques and context-awareness. To evaluate the platform, we carried out usability experiments and performance benchmarks.

  19. Internet-based surveillance systems for monitoring emerging infectious diseases.

    Science.gov (United States)

    Milinovich, Gabriel J; Williams, Gail M; Clements, Archie C A; Hu, Wenbiao

    2014-02-01

    Emerging infectious diseases present a complex challenge to public health officials and governments; these challenges have been compounded by rapidly shifting patterns of human behaviour and globalisation. The increase in emerging infectious diseases has led to calls for new technologies and approaches for detection, tracking, reporting, and response. Internet-based surveillance systems offer a novel and developing means of monitoring conditions of public health concern, including emerging infectious diseases. We review studies that have exploited internet use and search trends to monitor two such diseases: influenza and dengue. Internet-based surveillance systems have good congruence with traditional surveillance approaches. Additionally, internet-based approaches are logistically and economically appealing. However, they do not have the capacity to replace traditional surveillance systems; they should not be viewed as an alternative, but rather an extension. Future research should focus on using data generated through internet-based surveillance and response systems to bolster the capacity of traditional surveillance systems for emerging infectious diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The Chronic Kidney Disease Model: A General Purpose Model of Disease Progression and Treatment

    Directory of Open Access Journals (Sweden)

    Patel Uptal D

    2011-06-01

    Full Text Available Abstract Background Chronic kidney disease (CKD is the focus of recent national policy efforts; however, decision makers must account for multiple therapeutic options, comorbidities and complications. The objective of the Chronic Kidney Disease model is to provide guidance to decision makers. We describe this model and give an example of how it can inform clinical and policy decisions. Methods Monte Carlo simulation of CKD natural history and treatment. Health states include myocardial infarction, stroke with and without disability, congestive heart failure, CKD stages 1-5, bone disease, dialysis, transplant and death. Each cycle is 1 month. Projections account for race, age, gender, diabetes, proteinuria, hypertension, cardiac disease, and CKD stage. Treatment strategies include hypertension control, diabetes control, use of HMG-CoA reductase inhibitors, use of angiotensin converting enzyme inhibitors, nephrology specialty care, CKD screening, and a combination of these. The model architecture is flexible permitting updates as new data become available. The primary outcome is quality adjusted life years (QALYs. Secondary outcomes include health state events and CKD progression rate. Results The model was validated for GFR change/year -3.0 ± 1.9 vs. -1.7 ± 3.4 (in the AASK trial, and annual myocardial infarction and mortality rates 3.6 ± 0.9% and 1.6 ± 0.5% vs. 4.4% and 1.6% in the Go study. To illustrate the model's utility we estimated lifetime impact of a hypothetical treatment for primary prevention of vascular disease. As vascular risk declined, QALY improved but risk of dialysis increased. At baseline, 20% and 60% reduction: QALYs = 17.6, 18.2, and 19.0 and dialysis = 7.7%, 8.1%, and 10.4%, respectively. Conclusions The CKD Model is a valid, general purpose model intended as a resource to inform clinical and policy decisions improving CKD care. Its value as a tool is illustrated in our example which projects a relationship between

  1. Monitoring and accountability for the Pacific response to the non-communicable diseases crisis

    Directory of Open Access Journals (Sweden)

    Hilary Tolley

    2016-09-01

    Full Text Available Abstract Background Non-communicable diseases (NCD are the leading cause of premature death and disability in the Pacific. In 2011, Pacific Forum Leaders declared “a human, social and economic crisis” due to the significant and growing burden of NCDs in the region. In 2013, Pacific Health Ministers’ commitment to ‘whole of government’ strategy prompted calls for the development of a robust, sustainable, collaborative NCD monitoring and accountability system to track, review and propose remedial action to ensure progress towards the NCD goals and targets. The purpose of this paper is to describe a regional, collaborative framework for coordination, innovation and application of NCD monitoring activities at scale, and to show how they can strengthen accountability for action on NCDs in the Pacific. A key component is the Dashboard for NCD Action which aims to strengthen mutual accountability by demonstrating national and regional progress towards agreed NCD policies and actions. Discussion The framework for the Pacific Monitoring Alliance for NCD Action (MANA draws together core country-level components of NCD monitoring data (mortality, morbidity, risk factors, health system responses, environments, and policies and identifies key cross-cutting issues for strengthening national and regional monitoring systems. These include: capacity building; a regional knowledge exchange hub; innovations (monitoring childhood obesity and food environments; and a robust regional accountability system. The MANA framework is governed by the Heads of Health and operationalised by a multi-agency technical Coordination Team. Alliance membership is voluntary and non-conditional, and aims to support the 22 Pacific Island countries and territories to improve the quality of NCD monitoring data across the region. In establishing a common vision for NCD monitoring, the framework combines data collected under the WHO Global Framework for NCDs with a set of action

  2. Monitoring and accountability for the Pacific response to the non-communicable diseases crisis.

    Science.gov (United States)

    Tolley, Hilary; Snowdon, Wendy; Wate, Jillian; Durand, A Mark; Vivili, Paula; McCool, Judith; Novotny, Rachel; Dewes, Ofa; Hoy, Damian; Bell, Colin; Richards, Nicola; Swinburn, Boyd

    2016-09-10

    Non-communicable diseases (NCD) are the leading cause of premature death and disability in the Pacific. In 2011, Pacific Forum Leaders declared "a human, social and economic crisis" due to the significant and growing burden of NCDs in the region. In 2013, Pacific Health Ministers' commitment to 'whole of government' strategy prompted calls for the development of a robust, sustainable, collaborative NCD monitoring and accountability system to track, review and propose remedial action to ensure progress towards the NCD goals and targets. The purpose of this paper is to describe a regional, collaborative framework for coordination, innovation and application of NCD monitoring activities at scale, and to show how they can strengthen accountability for action on NCDs in the Pacific. A key component is the Dashboard for NCD Action which aims to strengthen mutual accountability by demonstrating national and regional progress towards agreed NCD policies and actions. The framework for the Pacific Monitoring Alliance for NCD Action (MANA) draws together core country-level components of NCD monitoring data (mortality, morbidity, risk factors, health system responses, environments, and policies) and identifies key cross-cutting issues for strengthening national and regional monitoring systems. These include: capacity building; a regional knowledge exchange hub; innovations (monitoring childhood obesity and food environments); and a robust regional accountability system. The MANA framework is governed by the Heads of Health and operationalised by a multi-agency technical Coordination Team. Alliance membership is voluntary and non-conditional, and aims to support the 22 Pacific Island countries and territories to improve the quality of NCD monitoring data across the region. In establishing a common vision for NCD monitoring, the framework combines data collected under the WHO Global Framework for NCDs with a set of action-orientated indicators captured in a NCD Dashboard for

  3. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

    DEFF Research Database (Denmark)

    Aziz, N A; Jurgens, C K; Landwehrmeyer, G B

    2009-01-01

    OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

  4. Research progress in early diagnosis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Meng-sha SUN

    2018-04-01

    Full Text Available Alzheimer's disease (AD is a kind of central nervous system degenerative disease with higher incidence, which has been paid increasing attention. The pathogenesis is not yet clear though it has been studied a lot. The existing theories focused on amyloid β-protein (Aβ deposit, hyperphosphorylation of tau and cholinergic neuronal loss. There is mainly symptomatic treatment which cannot reverse disease course. So early diagnosis is particularly important for prevention and treatment of AD. The article will review recent advances in the studies of early diagnosis of AD. It may help accurately diagnose the process from mild cognitive impairment (MCI to early AD and give advice on prevention and treatment. DOI: 10.3969/j.issn.1672-6731.2018.03.011

  5. Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry Registry

    NARCIS (Netherlands)

    Wanner, Christoph; Oliveira, João P.; Ortiz, Alberto; Mauer, Michael; Germain, Dominique P.; Linthorst, Gabor E.; Serra, Andreas L.; Maródi, László; Mignani, Renzo; Cianciaruso, Bruno; Vujkovac, Bojan; Lemay, Roberta; Beitner-Johnson, Dana; Waldek, Stephen; Warnock, David G.

    2010-01-01

    These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values over a span of ≥12 months before starting enzyme replacement

  6. Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.

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    Petra Steinacker

    Full Text Available BACKGROUND: Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß correlated with clinical subtypes of ALS and were of prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study including patients with ALS (N = 68 with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20, and age-matched controls (N = 40, cerebrospinal fluid (CSF levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35 were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02 and with longer disease duration (p = 0.01 and p = 0.01, respectively. CSF NfH(SMI35 was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01. High CSF NfH(SMI3 was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively. The ratios CSF NfH(SMI35/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each. CSF Progranulin decreased with ongoing disease (p = 0.04. CONCLUSIONS: This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP is linked to progressive neuro-axonal damage (increase of NfH(SMI35 and to progression of disease.

  7. Multimodal imaging of the disease progression of birdshot chorioretinopathy

    NARCIS (Netherlands)

    Teussink, M.M.; Veld, P.I. Huis In Het; Vries, L.A.M. de; Hoyng, C.B.; Klevering, B.J.; Theelen, T.

    2016-01-01

    PURPOSE: To study outer retinal deterioration in relation to clinical disease activity in patients with birdshot chorioretinopathy using fundus autofluorescence and spectral-domain optical coherence tomography (OCT). METHODS: A single-centre retrospective cohort study was carried out on 42 eyes of

  8. Progression of experimental chronic Aleutian mink disease virus infection

    DEFF Research Database (Denmark)

    Jensen, Trine Hammer; Chriél, Mariann; Hansen, Mette Sif

    2016-01-01

    Aleutian mink disease virus (AMDV) is found world-wide and has a major impact on mink health and welfare by decreasing reproduction and fur quality. In the majority of mink, the infection is subclinical and the diagnosis must be confirmed by serology or polymerase chain reaction (PCR). Increased ...

  9. The Role of Sarcosine, Uracil, and Kynurenic Acid Metabolism in Urine for Diagnosis and Progression Monitoring of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Georgios Gkotsos

    2017-02-01

    . None of the three metabolites can be used reliably for monitoring the progress of the disease.

  10. Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study.

    Science.gov (United States)

    Chang, Jia-Feng; Yeh, Jih-Chen; Chiu, Ya-Lin; Liou, Jian-Chiun; Hsiung, Jing-Ru; Tung, Tao-Hsin

    2017-01-01

    No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases. Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms. During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%). Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 20 YEARS OF PROGRESS IN DIARRHEAL DISEASE RESEARCH

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    Narain H. Punjabi

    2012-09-01

    Full Text Available When NAMRU started its collaboration work with the National Institute of Health, Research and Development (NIHRD, it became apparent that diarrheal disease was one of the most important causes of morbidity and mortality in Indonesia, especially in children. Many of the most important etiologic agents of diarrhea were not known and the percentage of diarrheas with an identifiable etiologic agent was very low. Since these early times NAMRU and NIHRD have worked together in all aspects of diarrheal disease research. Increased capabilities for the identification of bac­tériologie, parasitic and viral enteropathogens, new vaccines, and better treatment via oral rehydration solutions are some of the results of this collaboration.

  12. Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries.

    Science.gov (United States)

    Wall, Kristin M; Rida, Wasima; Haddad, Lisa B; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H; Latka, Mary H; Anzala, Omu; Sanders, Eduard J; Bekker, Linda-Gail; Edward, Vinodh A; Price, Matt A

    2017-03-01

    Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement pregnancy. Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted.

  13. Rapidly progressive periodontal disease associated with human immunodeficiency virus

    International Nuclear Information System (INIS)

    Hezaim, K.A.; Javed, F.; Askar, A.; Rasheed, A.A.

    2012-01-01

    Severe periodontal inflammation with generalized dental plaque accumulation, spontaneous and severe gingival bleeding, fungal infection, and inter dental papillae necrosis are presented in a patient infected with human immunodeficiency virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on the gingival mucosa in both jaws. DNA testing was performed to identify the periodontopathogens. The patient had no signs or symptoms of acquired immunodeficiency syndrome. This case-report presents the massive periodontal destruction that occurred in a patient infected with HIV. Therefore, it is highly recommended that patients infected with HIV should be regularly monitored to aid in early detection and to provide proper management of periodontal inflammatory conditions to minimize its destruction. (author)

  14. Geothermal resource areas database for monitoring the progress of development in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, J.D.; Lepman, S.R.; Leung, K.; Phillips, S.L.

    1981-01-01

    The Geothermal Resource Areas Database (GRAD) and associated data system provide broad coverage of information on the development of geothermal resources in the United States. The system is designed to serve the information requirements of the National Progress Monitoring System. GRAD covers development from the initial exploratory phase through plant construction and operation. Emphasis is on actual facts or events rather than projections and scenarios. The selection and organization of data are based on a model of geothermal development. Subjects in GRAD include: names and addresses, leases, area descriptions, geothermal wells, power plants, direct use facilities, and environmental and regulatory aspects of development. Data collected in the various subject areas are critically evaluated, and then entered into an on-line interactive computer system. The system is publically available for retrieval and use. The background of the project, conceptual development, software development, and data collection are described here. Appendices describe the structure of the database in detail.

  15. Aquatic Toxic Analysis by Monitoring Fish Behavior Using Computer Vision: A Recent Progress

    Directory of Open Access Journals (Sweden)

    Chunlei Xia

    2018-01-01

    Full Text Available Video tracking based biological early warning system achieved a great progress with advanced computer vision and machine learning methods. Ability of video tracking of multiple biological organisms has been largely improved in recent years. Video based behavioral monitoring has become a common tool for acquiring quantified behavioral data for aquatic risk assessment. Investigation of behavioral responses under chemical and environmental stress has been boosted by rapidly developed machine learning and artificial intelligence. In this paper, we introduce the fundamental of video tracking and present the pioneer works in precise tracking of a group of individuals in 2D and 3D space. Technical and practical issues suffered in video tracking are explained. Subsequently, the toxic analysis based on fish behavioral data is summarized. Frequently used computational methods and machine learning are explained with their applications in aquatic toxicity detection and abnormal pattern analysis. Finally, advantages of recent developed deep learning approach in toxic prediction are presented.

  16. Interleukin-6 and interleukin-10 gene polymorphisms and the risk of further periodontal disease progression.

    Science.gov (United States)

    Chatzopoulos, Georgios; Doufexi, Aikaterini-Ellisavet; Wolff, Larry; Kouvatsi, Anastasia

    2018-03-08

    Susceptible genotypes to periodontal disease are associated with disease onset and progression. The aim of this study was to examine the effect of gene polymorphisms on the risk of further disease progression and the need for further treatment among adults with chronic periodontal disease. Sixty-seven patients diagnosed with chronic periodontitis were grouped according to genotype status and risk of further progression of disease and tooth loss. All individuals were clinically evaluated for probing pocket depth, clinical attachment loss and bleeding on probing at baseline and 45 days after treatment. Blood samples were collected at baseline and genotyping of the polymorphisms in IL-6 (rs1800796) and IL-10 (rs1800872) genes were performed by PCR. Following DNA separation and genotyping, 65.7% of the patients were homozygous carriers of the IL-6 -572G and 49.3% were carriers of the IL-10 -592A allele. Individuals at risk of disease progression ranged from 7.5% to 62.7% based on the criteria used. Carriers of the IL-10 -592A allele were significantly associated with BOP ≥ 30% and therefore exhibited a higher risk of further periodontal breakdown (p = 0.018) with an odds ratio of 1.18. None of the other definitions of disease progression were significantly associated with the examined IL-6 and IL-10 genotypes (p > 0.05). IL-10 polymorphism was associated with an increased risk of further disease progression and the potential need for further treatment following non-surgical periodontal treatment. Susceptible IL-6 genotypes were not associated with the risk of persisting or recurrent disease activity.

  17. Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

    Science.gov (United States)

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Gomulkiewicz, Agnieszka; Glatzel-Plucinska, Natalia; Reich, Adam; Podhorska-Okołów, Marzenna; Dzięgiel, Piotr; Szepietowski, Jacek C

    2017-02-08

    The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

  18. Electrophysiological Monitoring of Injury ProgressionIn the Rat Cerebellar Cortex

    Directory of Open Access Journals (Sweden)

    Gokhan eOrdek

    2014-10-01

    Full Text Available The changes of excitability in affected neural networks can be used as a marker to study the temporal course of traumatic brain injury (TBI. The cerebellum is an ideal platform to study brain injury mechanisms at the network level using the electrophysiological methods. Within its crystalline morphology, the cerebellar cortex contains highly organized topographical subunits that are defined by two main inputs, the climbing and mossy fibers. Here we demonstrate the use of cerebellar evoked potentials (EPs mediated through these afferent systems for monitoring the injury progression in a rat model of fluid percussion injury (FPI. A mechanical tap on the dorsal hand was used as a stimulus, and EPs were recorded from the paramedian lobule (PML of the posterior cerebellum via multi-electrode arrays (MEA. Post-injury evoked response amplitudes (EPAs were analyzed on a daily basis for one week and compared with pre-injury values. We found a trend of consistently decreasing EPAs in all nine animals, losing as much as 72±4% of baseline amplitudes measured before the injury. Notably, our results highlighted two particular time windows; the first 24 hours of injury in the acute period and day-3 to day-7 in the delayed period where the largest drops (~50% and 24% were observed in the EPAs. In addition, cross-correlations of spontaneous signals between electrode pairs declined (from 0.47±0.1 to 0.35±0.04, p<0.001 along with the EPAs throughout the week of injury. In support of the electrophysiological findings, immunohistochemical analysis at day-7 post-injury showed detectable Purkinje cell loss at low FPI pressures and more with the largest pressures used. Our results suggest that sensory evoked potentials recorded from the cerebellar surface can be a useful technique to monitor the course of cerebellar injury and identify the phases of injury progression even at mild levels.

  19. RandomForest4Life: a Random Forest for predicting ALS disease progression.

    Science.gov (United States)

    Hothorn, Torsten; Jung, Hans H

    2014-09-01

    We describe a method for predicting disease progression in amyotrophic lateral sclerosis (ALS) patients. The method was developed as a submission to the DREAM Phil Bowen ALS Prediction Prize4Life Challenge of summer 2012. Based on repeated patient examinations over a three- month period, we used a random forest algorithm to predict future disease progression. The procedure was set up and internally evaluated using data from 1197 ALS patients. External validation by an expert jury was based on undisclosed information of an additional 625 patients; all patient data were obtained from the PRO-ACT database. In terms of prediction accuracy, the approach described here ranked third best. Our interpretation of the prediction model confirmed previous reports suggesting that past disease progression is a strong predictor of future disease progression measured on the ALS functional rating scale (ALSFRS). We also found that larger variability in initial ALSFRS scores is linked to faster future disease progression. The results reported here furthermore suggested that approaches taking the multidimensionality of the ALSFRS into account promise some potential for improved ALS disease prediction.

  20. Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer's Disease?

    Science.gov (United States)

    Harding, Alice; Robinson, Sarita; Crean, StJohn; Singhrao, Sim K

    2017-01-01

    A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P. gingivalis, to gain greater virulence. The initial process involves P. gingivalis disturbing neutrophil mediated innate immune responses in the healthy gingivae and then downregulating adaptive immune cell differentiation and development to invade, and subsequently, establish new dysbiotic bacterial communities. Immune responses affect the host in general and functionally via dietary adjustments caused by tooth loss. Studies from animals orally infected with P. gingivalis confirm this bacterium can transmigrate to distant organ sites (the brain) and contribute toward peripheral and intracerebral inflammation, and compromise vascular and microvascular integrity. In another study, P. gingivalis infection caused sleep pattern disturbances by altering glial cell light/dark molecular clock activity, and this, in turn, can affect the clearance of danger associated molecular patterns, such as amyloid-β, via the glymphatic system. Since P. gingivalis can transmigrate to the brain and modulate organ-specific inflammatory innate and adaptive immune responses, this paper explores whether better management of indigenous periodontal bacteria could delay/prevent the onset and/or progression of dementia.

  1. Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy.

    Science.gov (United States)

    Albonico, M; Levecke, B; LoVerde, P T; Montresor, A; Prichard, R; Vercruysse, J; Webster, J P

    2015-12-01

    In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  2. Prion protein polymorphisms affect chronic wasting disease progression.

    Directory of Open Access Journals (Sweden)

    Chad J Johnson

    Full Text Available Analysis of the PRNP gene in cervids naturally infected with chronic wasting disease (CWD suggested that PRNP polymorphisms affect the susceptibility of deer to infection. To test this effect, we orally inoculated 12 white-tailed deer with CWD agent. Three different PRNP alleles, wild-type (wt; glutamine at amino acid 95 and glycine at 96, Q95H (glutamine to histidine at amino acid position 95 and G96S (glycine to serine at position 96 were represented in the study cohort with 5 wt/wt, 3 wt/G96S, and 1 each wt/Q95H and Q95H/G96S. Two animals were lost to follow-up due to intercurrent disease. The inoculum was prepared from Wisconsin hunter-harvested homozygous wt/wt animals. All infected deer presented with clinical signs of CWD; the orally infected wt/wt had an average survival period of 693 days post inoculation (dpi and G96S/wt deer had an average survival period of 956 dpi. The Q95H/wt and Q95H/G96S deer succumbed to CWD at 1,508 and 1,596 dpi respectively. These data show that polymorphisms in the PRNP gene affect CWD incubation period. Deer heterozygous for the PRNP alleles had extended incubation periods with the Q95H allele having the greatest effect.

  3. The progression of coeliac disease: its neurological and psychiatric implications.

    Science.gov (United States)

    Campagna, Giovanna; Pesce, Mirko; Tatangelo, Raffaella; Rizzuto, Alessia; La Fratta, Irene; Grilli, Alfredo

    2017-06-01

    The aim of the paper is to show the various neurological and psychiatric symptoms in coeliac disease (CD). CD is a T cell-mediated, tissue-specific autoimmune disease which affects genetically susceptible individuals after dietary exposure to proline- and glutamine-rich proteins contained in certain cereal grains. Genetics, environmental factors and different immune systems, together with the presence of auto-antigens, are taken into account when identifying the pathogenesis of CD. CD pathogenesis is related to immune dysregulation, which involves the gastrointestinal system, and the extra-intestinal systems such as the nervous system, whose neurological symptoms are evidenced in CD patients. A gluten-free diet (GFD) could avoid cerebellar ataxia, epilepsy, neuropathies, migraine and mild cognitive impairment. Furthermore, untreated CD patients have more symptoms and psychiatric co-morbidities than those treated with a GFD. Common psychiatric symptoms in untreated CD adult patients include depression, apathy, anxiety, and irritability and schizophrenia is also common in untreated CD. Several studies show improvement in psychiatric symptoms after the start of a GFD. The present review discusses the state of the art regarding neurological and psychiatric complications in CD and highlights the evidence supporting a role for GFD in reducing neurological and psychiatric complications.

  4. Understanding Climate Adaptation on Public Lands in the Upper Midwest: Implications for Monitoring and Tracking Progress

    Science.gov (United States)

    Anhalt-Depies, Christine M.; Knoot, Tricia Gorby; Rissman, Adena R.; Sharp, Anthony K.; Martin, Karl J.

    2016-05-01

    There are limited examples of efforts to systematically monitor and track climate change adaptation progress in the context of natural resource management, despite substantial investments in adaptation initiatives. To better understand the status of adaptation within state natural resource agencies, we utilized and problematized a rational decision-making framework to characterize adaptation at the level of public land managers in the Upper Midwest. We conducted in-depth interviews with 29 biologists and foresters to provide an understanding of managers' experiences with, and perceptions of, climate change impacts, efforts towards planning for climate change, and a full range of actions implemented to address climate change. While the majority of managers identified climate change impacts affecting their region, they expressed significant uncertainty in interpreting those signals. Just under half of managers indicated planning efforts are underway, although most planning is remote from local management. Actions already implemented include both forward-looking measures and those aimed at coping with current impacts. In addition, cross-scale dynamics emerged as an important theme related to the overall adaptation process. The results hold implications for tracking future progress on climate change adaptation. Common definitions or measures of adaptation (e.g., presence of planning documents) may need to be reassessed for applicability at the level of public land managers.

  5. Effect of low-protein diet supplemented with keto acids on progression of chronic kidney disease.

    Science.gov (United States)

    Garneata, Liliana; Mircescu, Gabriel

    2013-05-01

    Hypoproteic diets are most often discussed for patients with chronic kidney disease (CKD) who do not receive dialysis. A very low-protein diet supplemented with ketoanalogues of essential amino acids (keto-diet) proved effective in ameliorating metabolic disturbances of advanced CKD and delaying the initiation of dialysis without deleterious effects on nutritional status. Several recent studies report that the keto-diet could also slow down the rate of decline in renal function, with better outcomes after the initiation of dialysis. Results of a single-center randomized controlled trial addressing the rate of CKD progression revealed a 57% slower decline in renal function with the keto-diet compared with a conventional low-protein diet (LPD). The keto-diet allowed the safe management of selected patients with stage 4-5 CKD, delaying dialysis for almost 1 year, with a major impact on patient quality of life and health expenditures. Therefore, the keto-diet could be a link in the integrated care model. Careful selection of patients, nutritional monitoring, and dietary counseling are required. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review.

    Science.gov (United States)

    Requena-Méndez, Ana; López, Manuel Carlos; Angheben, Andrea; Izquierdo, Luis; Ribeiro, Isabela; Pinazo, Maria-Jesús; Gascon, Joaquim; Muñoz, José

    2013-09-01

    This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.

  7. Pulmonary Hypertension Due to Left Ventricular Cardiomyopathy: Is it the Result or Cause of Disease Progression?

    Science.gov (United States)

    Adusumalli, Srinath; Mazurek, Jeremy A

    2017-12-01

    The purpose of this review is to define pulmonary hypertension in the setting of left heart disease (PH-LHD), discuss its epidemiology and pathophysiology, and highlight the cause and effect relationship it has with disease progression in the setting of cardiomyopathy. Both pulmonary hypertension (PH) and heart failure are becoming increasingly common. As such, PH-LHD is now the most common form of PH. The pathophysiology of the condition relates to backward transmission of elevated left ventricular filling pressures into the pulmonary circulation and, ultimately, right ventricular (RV) strain/dysfunction. It is evident that these pathophysiologic processes are both the effect and cause of left heart disease progression. In this review, we describe the complex relationship between disease progression in left ventricular cardiomyopathy and PH-LHD. Clinicians and researchers should take note of the importance of PH-LHD and RV dysfunction to appropriately risk stratify patients and develop therapies for the condition.

  8. Research progress of antagonistic interactions among root canal irrigations disease

    Directory of Open Access Journals (Sweden)

    Chen QU

    2013-07-01

    Full Text Available Root canal therapy is the most effective way to treat various pulposis and periapical disease. Simple mechanical apparatus can not clean root canal thoroughly, but may affect tight filling instead. It can achieve a satisfactory cleansing effect only when it is combined with a chemical solution. Irrigation fluid for root canal should possess the properties of tissue dissolution, antimicrobial, lubrication, and removal of smear layer. So far, no solution is able to fulfill all these functions. Therefore, a combined use of multiple irrigation solutions is suggested. It can not only achieve good effect in cleaning and disinfection, also it can lower the concentration of different solutions, thus reducing the side effects. Nevertheless, some experiments proved that antagonism existed among the chemicals used for irrigations. The purpose of present article is to review the antagonistic effect among the chemicals used for irrigation when they are used together for root canal treatment.

  9. A Blood Test for Alzheimer's Disease: Progress, Challenges, and Recommendations.

    Science.gov (United States)

    Kiddle, Steven J; Voyle, Nicola; Dobson, Richard J B

    2018-03-29

    Ever since the discovery of APOEɛ4 around 25 years ago, researchers have been excited about the potential of a blood test for Alzheimer's disease (AD). Since then researchers have looked for genetic, protein, metabolite, and/or gene expression markers of AD and related phenotypes. However, no blood test for AD is yet being used in the clinical setting. We first review the trends and challenges in AD blood biomarker research, before giving our personal recommendations to help researchers overcome these challenges. While some degree of consistency and replication has been seen across independent studies, several high-profile studies have seemingly failed to replicate. Partly due to academic incentives, there is a reluctance in the field to report predictive ability, to publish negative findings, and to independently replicate the work of others. If this can be addressed, then we will know sooner whether a blood test for AD or related phenotypes with clinical utility can be developed.

  10. Progress in the molecular diagnosis of Lyme disease.

    Science.gov (United States)

    Ružić-Sabljić, Eva; Cerar, Tjaša

    2017-01-01

    Current laboratory testing of Lyme borreliosis mostly relies on serological methods with known limitations. Diagnostic modalities enabling direct detection of pathogen at the onset of the clinical signs could overcome some of the limitations. Molecular methods detecting borrelial DNA seem to be the ideal solution, although there are some aspects that need to be considered. Areas covered: This review represent summary and discussion of the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) together with our own experience on molecular diagnosis of Lyme disease. Expert commentary: Molecular methods are promising and currently serve as supporting diagnostic testing in Lyme borreliosis. Since the field of molecular diagnostics is under rapid development, molecular testing could become an important diagnostic modality.

  11. Task and Progress of Iaeg-Sdgs Wggi in Monitoring Sdgs Through a `GEOGRAPHIC Location' Lens

    Science.gov (United States)

    Geng, W.; Chen, J.; Zhang, H. P.; Xu, K.

    2018-04-01

    In September 2015, the 193 Member States of the United Nations (UN) unanimously adopted the 2030 Agenda for Sustainable Development and its 17 Sustainable Development Goals (SDGs), aiming to transform the world over the next 15 years (ESDN, 2016). To meet the ambitions and demands of the 2030 Agenda, it is necessary for the global indicator framework to adequately and systematically address the issue of alternative data sources and methodologies, including geospatial information and Earth observations in the context of geographic location (UN-GGIM, 2016). For this purpose, the Inter-Agency and Expert Group on Sustainable Development Goals Indicator (IAEG-SDGs) created the Working Group on Geospatial Information (IAEG-SDGs: WGGI) to give full play to the role of geospatial data in SDGs measurement and monitoring. The Working Group reviewed global indicators through a `geographic location' lens to pick out those which geospatial information can significantly support the production, and analyzed the methodological and measurements issues. This paper has discussed the progress in monitoring SDGs ever since the establishment of IAEG-SDGs: WGGI, as well as the existing problems, appropriate solutions and plans for the next stage of work.

  12. Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

    Directory of Open Access Journals (Sweden)

    James R Roede

    Full Text Available Progression of Parkinson's disease (PD is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

  13. Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

    Science.gov (United States)

    Roede, James R; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H; Rhodes, Shannon L; Ritz, Beate; Jones, Dean P

    2013-01-01

    Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

  14. Uraemia progression in chronic kidney disease stages 3-5 is not constant

    DEFF Research Database (Denmark)

    Heaf, James Goya; Mortensen, Leif Spange

    2011-01-01

    Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m(2)/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimated...... GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating....

  15. Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A Spectrum of the Same Disease?

    Directory of Open Access Journals (Sweden)

    Irina Khamaganova

    2018-01-01

    Full Text Available Similar clinical and histhopathological features in progressive hemifacial atrophy and linear scleroderma en coup de sabre are well known. Trauma may predispose to the development of both diseases. The lack of association with anti-Borrelia antibodies was shown in both cases as well. The otolaryngological and endocrine disorders may be associated findings in both diseases. However, there are certain differences in neurological and ophthalmological changes in the diseases.

  16. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    Science.gov (United States)

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. © 2015 The Author(s) Published by S. Karger AG, Basel.

  17. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Xin Wu

    2015-11-01

    Full Text Available Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD in humans and non-human primates (NHPs. Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs, vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirus∆VP30, recombinant cytomegalovirus (CMV-based vaccines, recombinant rabies virus (RABV-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

  18. Progress with infliximab biosimilars for inflammatory bowel disease.

    Science.gov (United States)

    Kurti, Zsuzsanna; Gonczi, Lorant; Lakatos, Peter L

    2018-04-29

    Biological therapies have revolutionized the treatment of inflammatory bowel diseases (IBD) in the last two decades. Though biological drugs are effective, their use is associated with high costs and access to biological agents varies among countries. As the patent for the reference products expired, the advent of biosimilar monoclonal antibodies has been expected. Biosimilars represent less expensive alternatives compared to the reference product. Areas covered: In this review, authors will review the literature on the clinical efficacy, safety and immunogenicity of current and future biosimilar infliximabs. Short- and medium-term data from real-life cohorts and from randomized-clinical trials in IBD demonstrated similar outcomes in terms of efficacy, safety and immunogenicity as the reference product for CT-P13. Switch data from the reference to the biosimilar product are also accumulating (including the NOR-SWITCH and the CT-P13 3.4 study). Expert opinion: The use of biosimilar infliximab in IBD is increasing worldwide. Its use may be associated with budget savings leading to better access to biological therapies and consequently improved health outcomes. Switching from the originator to a biosimilar in patients with IBD is acceptable, although scientific and clinical evidence is lacking regarding reverse switching, multiple switching, and cross-switching among biosimilars in IBD patients.

  19. Salivary DJ-1 could be an indicator of Parkinson’s disease progression

    Directory of Open Access Journals (Sweden)

    Wen-yan eKang

    2014-06-01

    Full Text Available Objective: The goal of the current investigation was to explore whether salivary DJ-1 could be a potential biomarker for monitoring disease progression in Parkinson’s disease (PD by evaluating the association between salivary DJ-1 concentrations and nigrostriatal dopaminergic function.Methods: First, in 74 patients with PD and 12 age-matched normal controls, single photon emission computed tomography (SPECT imaging with labeled dopamine transporters (DAT (99mTc-TRODAT-1, which has been used for measuring DAT density in PD was prformed. Then, the DJ-1 level in their saliva was analyzed by quantitative and sensitive Luminex assay and compared to caudate or putamen DAT density. Finally, based on the above, our cross-section study was carried out in 376 research volunteers (285 patients with PD and 91 healthy controls to measure salivary DJ-1 level.Results: From our analysis, we found a correlation between salivary concentration of DJ-1 and putamen nucleus uptake of 99mTc-TRODAT-1 in the PD group. Although salivary DJ-1 levels were not affected by UPDRS scores, gender, age and pharmacotherapy, DJ-1 levels in H&Y 4 stage of PD were higher than those in H&Y 1-3 stage as well as those in healthy controls. Salivary DJ-1 also decreased significantly in mixed type PD patients compared to the tremor-dominant type (TDT and akinetic-rigid dominant type (ARDT PD patients.Conclusions: According to the investigation in a large cohort, we reported for the first time the prognostic potential of the salivary DJ-1 as a biomarker for evaluating nigrostriatal dopaminergic function in PD.

  20. [Natural progression of premature pubarche and underlying diseases].

    Science.gov (United States)

    Sancho Rodríguez, María Luisa; Bueno Lozano, Gloria; Labarta Aizpún, José Ignacio; de Arriba Muñoz, Antonio

    2018-04-25

    Premature pubarche (PP) is generally thought to be a benign condition, but it can also be the first sign of underlying disease. To analyse the aetiology and the evolution of the anthropometric, analytical and metabolic risk parameters of a group of patients with PP. A descriptive and analytical retrospective study of 92 patients affected by PP. Anthropometry, analyses, bone age and indicators of lipid metabolism were all evaluated. The sample included 92 patients with PP (67 female and 25 male), with a mean age of 7.1±0.6 for girls and 8.3±0.7 for boys. Small for gestational age was recorded in 7.7%. There was an accelerated bone age (1.20±0.1 years). A total of 21 patients were classified as idiopathic (23%), 60 as idiopathic premature adrenarche (65%), and 11 with non-classic congenital adrenal hyperplasia (12%). Puberty was reached early (11+0.9 years old in boys and 9.9±0.8 in girls), as was menstruation age (11.8+1.1 years old), P<.001. The stature finally reached was close to their genetic stature. There is a positive correlation between body mass index, blood glucose and LDL cholesterol, as well as a tendency towards hyperinsulinaemia. The present study shows that PP is a benign condition in the majority of cases, but non-classic congenital adrenal hyperplasia (12%) is not uncommon. Menstruation and puberty started early and bone age was accelerated. Growth was normal, and more or less in line with genetic size. PP associated with obesity is linked with analytical variations of metabolic risks. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  1. Pharmacogenetics: progress, pitfalls and clinical potential for coronary heart disease.

    Science.gov (United States)

    Humphries, Steve E; Hingorani, Aroon

    2006-02-01

    Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usual approach has been opportunistic use of drug trials in unrelated patients, and to look for differences in response or outcome by "candidate gene" genotype, for example genes coding for drug metabolising enzymes (activators and metabolisers), and enzymes and receptors involved in lipid metabolism, adrenergic response, etc. As with all association studies, initially promising results have often failed the test of replication in larger studies, and the relationship between the CETP Taq-I variant and response to statins has now been disproved. The strongest data to date is the report [Chasman, D.I., Posada, D., Subrahmanyan, L., Cook, N.R., Stanton Jr., V.P., Ridker, P.M., 2004. Pharmacogenetic study of statin therapy and cholesterol reduction. J. Am. Med. Assoc. 291, 2821-2827] of a poorer cholesterol-lowering response to Pravastatin in the 7% of patients carrying a certain haplotype of the HMG CoA reductase gene (14% fall versus 19%), but if this is overcome simply by a higher dose, it is of little clinical relevance. Currently, the best example of avoiding side effects is determining genotype at the CYP2C9 locus with respect of warfarin treatment, since carriers for functional variants (>20% of the population) require lower doses for optimal anticoagulation, and homozygotes, although rare, may well experience serious bleeding if given a usual dose. The full potential of this field will only be realised with much further work.

  2. Putaminal serotonergic innervation: monitoring dyskinesia risk in Parkinson disease.

    Science.gov (United States)

    Lee, Jee-Young; Seo, Seongho; Lee, Jae Sung; Kim, Han-Joon; Kim, Yu Kyeong; Jeon, Beom S

    2015-09-08

    To explore serotonergic innervation in the basal ganglia in relation to levodopa-induced dyskinesia in patients with Parkinson disease (PD). A total of 30 patients with PD without dementia or depression were divided into 3 matched groups (dyskinetic, nondyskinetic, and drug-naive) for this study. We acquired 2 PET scans and 3T MRI for each patient using [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ((11)C-DASB) and N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane ((18)F-FP-CIT). Then we analyzed binding potentials of the 2 radiotracers at basal ganglia structures and correlations with clinical variables. We observed no difference in (18)F-FP-CIT binding between dyskinetic and nondyskinetic patients, whereas there were differences in (11)C-DASB binding for the caudate and putamen. Binding potential ratios ((11)C-DASB/(18)F-FP-CIT) at the putamen, which indicate serotoninergic fiber innervation relative to dopaminergic fiber availability, were highest in the dyskinetic group, followed by the nondyskinetic and drug-naive PD groups. (11)C-DASB/(18)F-FP-CIT ratios at the putamen and pallidum correlated positively with Unified Parkinson's Disease Rating Scale (UPDRS) total scores and duration of PD, and pallidal binding ratio also correlated with the UPDRS motor scores. Ratios were not dependent on dopaminergic medication dosages for any of the regions studied. Relative serotonergic innervation of the putamen and pallidum increased with clinical PD progression and was highest in patients with established dyskinesia. The serotonin/dopamine transporter ratio might be a potential marker of disease progression and an indicator of risk for levodopa-induced dyskinesia in PD. A prospective evaluation is warranted in the future. © 2015 American Academy of Neurology.

  3. Retarding chronic kidney disease (CKD progression: a practical nutritional approach for non-dialysis CKD

    Directory of Open Access Journals (Sweden)

    Vincenzo Bellizzi

    2016-10-01

    Full Text Available This is a case report on a patient with non-dialysis chronic kidney disease (CKD in whom several nutritional issues are briefly discussed from a practical point of view. The article is accompanied by an editorial published in this Journal in relation to the 2nd International Conference of the European Renal Nutrition working group at ERA-EDTA—“Retarding CKD progression: readily available through comprehensive nutritional management?”—and focuses on several practical topics associated with the nutritional approach for the conservative treatment of non-dialysis CKD. The article is divided into 3 sections—basic nutritional assessment, nutritional targets, and nutritional follow-up in non-dialysis CKD—linked to 3 consecutive steps of the clinical follow-up of the patient and the related nutritional concerns and intervention. First visit: Baseline nutritional assessment and basic nutritional considerations in non-dialysis chronic kidney disease (CKD • What nutritional assessment/monitoring for protein-energy wasting (PEW should be employed? • Is a body mass index (BMI of 21 kg/m2 adequate? • What phosphate target should be pursued? • What are the nutritional habits in patients with incident CKD? • What protein needs and amount of dietary protein should be pursued? • Does the quality of protein matter? • What amount of dietary salt should be employed? How should this be obtained? • How should normal serum phosphate be achieved? • What diet should be recommended? Is a vegetarian diet an option? Second visit: Major nutritional targets in non-dialysis CKD • Consequences of unintentional weight loss • What is the role of the renal dietitian in helping the patient adhere to a renal diet? Intermediate visits: Nutritional follow-up in non-dialysis CKD • What treatment for calcium/parathyroid hormone (PTH will affect CKD progression? Final visits: • Would a dietary recall/intensive dietary education improve adherence with

  4. Research progress in role of iron overload in non-alcoholic fatty liver disease

    OpenAIRE

    LI Guangming

    2013-01-01

    Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD). The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iro...

  5. MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Yasmina Bauer

    2017-03-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7, Fas death receptor ligand, osteopontin and procollagen type I C-peptide, to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.

  6. Characterization of annual disease progression of multiple sclerosis patients: A population-based study

    DEFF Research Database (Denmark)

    Freilich, Jonatan; Manouchehrinia, Ali; Trusheim, Mark

    2017-01-01

    Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan-Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching...... the milestone. To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS). The annual progression of 11,964 patients from the Swedish MS Registry was analysed with 10 multinomial logistic regressions, that is, one for transition...... from each full EDSS with explanatory variables age, sex, age at onset, time in current EDSS, highest prior EDSS, MS course and treatment. All factors (except sex) investigated had statistically significant impacts on transitions from at least one EDSS. However, significance and size of the effect...

  7. EFFECT OF ALTITUDE AND WOUNDING ON BLOOD DISEASE PROGRESS OF PLANTAIN

    Directory of Open Access Journals (Sweden)

    Hadiwiyono, S. Subandiyah, C. Sumardiyono, J. Widada, and M. Fegan.

    2012-02-01

    Full Text Available Effect of Altitude and Wounding on Blood Disease Progress of Plantain. In the latest decade, the blood disease of banana has spread in almost all provinces in Indonesia and caused wilting of millions banana clusters in several provinces.  It is very difficult to control the disease due  to the base data about ecology and epidemiology of the pathogen are still poorly understood. This research aimed to evaluate the effect of  wounding of inoculation site on blood disease progress of plantain. The experiment was arranged using randomized completely block design It was conducted at three locations with altitude of 100, 1000, and 1600 m above sea levels as replication block. The treatments were wounding, unwounding inoculation site, inoculation, and uninoculation of plantain cv. Kepok Kuning Wounding was applied by stabbing with an injection pin around the corm of 15 stabs/seedling. The seedlings were planted singly in one liter of non sterile soil in plastic bag.  Each treatment consisted of 5 seedlings which was replicated 3 times. Inoculation was done  by soil drenching of 20 ml bacterial suspension at  concentration of 108 cfu/ml two week after planting.  The pathogen used for inoculation originated from low land area (about 100 m above sea level.  Observation was done weekly for 5 weeks. The variables observed were wilt intensity and area under disease progress (AUDPC. The results showed that blood disease was able to establish at altitude of 1600 m above sea level. The disease progress however was slower that those at 100 and 1000 m above sea level. On wounded seedling, the disease progress was more aggressive than those on unwounded one.

  8. Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Knudsen, T B; Kristiansen, T B; Katzenstein, T L

    2001-01-01

    /G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently......HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A...

  9. Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings.

    Science.gov (United States)

    Maglione, Paul J; Overbey, Jessica R; Cunningham-Rundles, Charlotte

    2015-01-01

    Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. Copyright © 2015 American Academy of Allergy

  10. Qualitative and quantitative analysis of diffusion-weighted imaging of gestational trophoblastic disease: Can it predict progression of molar pregnancy to persistent form of disease?

    Energy Technology Data Exchange (ETDEWEB)

    Sefidbakht, Sepideh [Medical imaging research center, Department of Radiology and Imaging, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Hosseini, Fatemeh, E-mail: f.hoseini88@gmail.com [Medical imaging research center, Department of Radiology and Imaging, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Bijan, Bijan [Abdominal Imaging/MR and Nonvascular Interventional Division, University of California, Davis, CA (United States); Hamedi, Bahareh; Azizi, Tayyebeh [Obstetrics& Gynecology Department, Medical School, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)

    2017-03-15

    Highlights: • The incidence of GTD in Iran is significantly higher than America and Europe. • ADC value of GTD is (1.96 ± 0.32 × 10{sup −3} mm{sup 2}/s). • GTD in T1 and T2-weighted images shows heterogeneous “snow-storm” appearance. • Focal intratumoral hemorrhage is bright in DWI and low signal in the ADC map. • ADC value and DWI are not helpful to predict progression of HM to persistent disease. - Abstract: Purpose: To describe the diffusion-weighted imaging (DWI) appearance of gestational trophoblastic disease (GTD) and to determine its apparent diffusion coefficient (ADC) values. To evaluate the feasibility of DWI to predict progression of hydatidiform mole (HM) to persistent disease. Methods: During a period of 6 months, women with preliminary diagnosis of GTD, based on ultrasound and ßhCG levels, underwent 1.5T MRI (T2 high-resolution and DWI; b values 50, 400, 800; sagittal and perpendicular to the endometrium; and T1, T2 Turbo Spin Echo [TSE] axial images). Patients were followed for 6–12 months to monitor progression to persistent form of the disease. ADC values and image characteristics were compared between HM and persistent neoplasia and between GTD and non-molar pregnancy using Mann–Whitney U and Fisher’s exact tests, respectively. Results: Among the 23 studied patients, 19 (83%) were classified as molar and 4 (17%) as non-molar, based on pathology reports. After 6–12 months of follow-up, 5 (26%) cases progressed to persistent disease and 14 (74%) cases were benign HM. There was no significant difference between ADC values for HM (1.93 ± 0.33 × 10{sup −3} mm{sup 2}/s) and persistent neoplasia (2.03 ± 0.28 × 10{sup −3} mm{sup 2}/s) (P = 0.69). The ADC of non-molar pregnancies was (0.96 ± 0.46 × 10{sup −3} mm{sup 2}/s), which was significantly different from GTD (1.96 ± 0.32 × 10{sup −3} mm{sup 2}/s) (P = 0.001). Heterogeneous snowstorm appearance, focal intratumoral hemorrhage, myometrial contraction, and

  11. Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats

    Directory of Open Access Journals (Sweden)

    Farzad Shidfar

    2018-01-01

    Full Text Available Background: Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease (NAFLD. However, the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD are not clear enough. The aim of this study was to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD prognosis. Methods: Forty male Sprague–Dawley rats (197±4 g were randomly assigned to 4 dietary groups: normal-fat diet (NFD; receiving 9% of calories as fat, high-fat diet (HFD; receiving 82% of calories as fat, supplementation before disease progression (S+HFD, and supplementation after disease progression (HFD+S. The diets were implemented over a 20-week period in all the groups. Biochemical and histologic parameters were compared between the 4 groups, and between-group comparisons were also carried out. Results: There were significant differences in the average food dietary intake (P<0.001, weight (P<0.001, fasting blood sugar (P=0.005, triglyceride (P<0.001, total cholesterol (P<0.001, low-density lipoprotein cholesterol (P=0.002, high-density lipoprotein cholesterol (P=0.001, alanine aminotransferase (P<0.001, and aspartate aminotransferase (P<0.001 between the 4 dietary groups. Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group (P<0.001 and P=0.003, respectively. Fat accumulation was significantly reduced in the HFD+S Group (P<0.001. Conclusion: Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD.

  12. Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats.

    Science.gov (United States)

    Shidfar, Farzad; Faghihi, Amirhosein; Amiri, Hamid Lorvand; Mousavi, Seyedeh Neda

    2018-01-01

    Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease (NAFLD). However, the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD are not clear enough. The aim of this study was to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD prognosis. Forty male Sprague-Dawley rats (197±4 g) were randomly assigned to 4 dietary groups: normal-fat diet (NFD; receiving 9% of calories as fat), high-fat diet (HFD; receiving 82% of calories as fat), supplementation before disease progression (S+HFD), and supplementation after disease progression (HFD+S). The diets were implemented over a 20-week period in all the groups. Biochemical and histologic parameters were compared between the 4 groups, and between-group comparisons were also carried out. There were significant differences in the average food dietary intake (P<0.001), weight (P<0.001), fasting blood sugar (P=0.005), triglyceride (P<0.001), total cholesterol (P<0.001), low-density lipoprotein cholesterol (P=0.002), high-density lipoprotein cholesterol (P=0.001), alanine aminotransferase (P<0.001), and aspartate aminotransferase (P<0.001) between the 4 dietary groups. Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group (P<0.001 and P=0.003, respectively). Fat accumulation was significantly reduced in the HFD+S Group (P<0.001). Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD.

  13. Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

    Science.gov (United States)

    Whiteman, Maura K; Jeng, Gary; Samarina, Anna; Akatova, Natalia; Martirosyan, Margarita; Kissin, Dmitry M; Curtis, Kathryn M; Marchbanks, Polly A; Hillis, Susan D; Mandel, Michele G; Jamieson, Denise J

    2016-01-01

    To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to contraceptive method. During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Published by Elsevier Inc.

  14. Repeat interventions as a long-term treatment strategy in the management of progressive coronary artery disease.

    NARCIS (Netherlands)

    K.G. Lehmann (Kenneth); P.W.J.C. Serruys (Patrick); M.J.B.M. van den Brand (Marcel); P.J. de Feyter (Pim); A.C.P. Maas (Arthur); R.T. van Domburg (Ron)

    1996-01-01

    textabstractObjectives. This study investigates whether repeat coronary interventions, applied over an extended time period, can successfully curtail the progression of ischemic symptoms and angiographic lumen narrowing. Background. Coronary artery disease is a chronic and generally progressive

  15. White matter disease correlates with lexical retrieval deficits in primary progressive aphasia

    Directory of Open Access Journals (Sweden)

    John P. Powers

    2013-12-01

    Full Text Available Objective: To relate fractional anisotropy changes associated with the semantic and logopenic variants of primary progressive aphasia to measures of lexical retrieval.Methods: We collected neuropsychological testing, volumetric MRI, and diffusion-weighted imaging on semantic variant primary progressive aphasia (n=11 and logopenic variant primary progressive aphasia (n=13 patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n=34. Fractional anisotropy was calculated and analyzed using a white matter tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to fractional anisotropy and determine regions of reduced fractional anisotropy in patients. Results: We found widespread fractional anisotropy reductions in white matter for both variants of primary progressive aphasia. Fractional anisotropy was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in semantic variant primary progressive aphasia and left superior and inferior longitudinal fasciculi in logopenic variant primary progressive aphasia. Conclusions: Semantic variant primary progressive aphasia and logopenic variant primary progressive aphasia are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the white matter disease in each phenotype may contribute to language impairments including lexical retrieval.

  16. Monitoring of total body water to examine the progress of acclimatization of runners at varying altitudes

    Directory of Open Access Journals (Sweden)

    Miroslav Semerád

    2017-11-01

    Full Text Available The purpose of our pilot study was to find out if total body water (TBW changes could objectively modify the course of adaptation during training for elite runners at different altitudes. The aim of this pilot study is to summarize the indication of the progress of acclimatization at high altitudes (1000–2700 meters above sea level during alpine conditioning. In three training camps at various altitudes the TBW of elite runners (F = 3, M = 1; n = 4; age 23 } 0.9 was monitored, in order to check the progress of acclimatization. We used BIA measurement methods (Bodystat 1500 at different high altitude running camps at the Czech Republic, Morocco and Ethiopia. Changes in TBW were used to check the progress of acclimatization. We discovered that the retention peaks of TBW corresponded with critical days (p ≤ 0.04; Cohen’s d. The highest measured increases of TBW at an altitude of 1000 m were for runner 1, 1.7 litres and for runner 2, 2.1 litres with retention peaks for both occurring on the 5th day. At an altitude of 1770 m runner 1 reached an increase of TBW of 6.3 litres, with a retention peak on the 11th day, and runner 3 had an increase of 5.1 litres with a peak on the 8th day. In the acclimatization phase we found two critical periods, from the 4th–6th day, and after the 10th–12th day. For runner 4 in altitude 2700m who completed the camp at a higher altitude, the situation is more complicated because there were fluctuations of the content of TBW in the range of 1.25 litres, with the highest depression on the 5th and then again an unsettled rise and reaching a maximum on the 12th, when she nearly returned to the initial value. Detected retention peaks reflected different levels of altitude (5th–12th days.We can conclude that the measuring of changes in TBW during camps at higher altitudes may be one of the biomarkers during acclimatization to altitude.

  17. JAK2V617F mutation in chronic myeloid leukemia predicts early disease progression

    International Nuclear Information System (INIS)

    Pahore, Z.A.A.; Shamsi, T.S.; Taj, M.; Farzana, T.; Ansari, S.H.; Nadeem, M.; Ahmad, M.; Naz, A.

    2011-01-01

    Objective: To determine the association of JAK2V617F mutation along with BCR-ABL translocation or Philadelphia chromosome in chronic myeloid leukemia with early disease progression to advanced stages (accelerated phase or blast crisis) and poor outcome. Study Design: Case series. Place and Duration of Study: National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, from February 2008 to August 2009. Methodology: All the newly diagnosed cases of BCR-ABL or Philadelphia positive CML were tested for JAK2V617F mutation by Nested PCR. Demographic data, spleen size, hemoglobin levels, white blood cell and platelet counts were recorded. Independent sample t-test was used for age, haemoglobin level and spleen size. Fisher's exact test was applied to compare disease progression in JAK2V617F mutation positive and negative cases. Results: Out of 45 newly diagnosed cases of CML, 40 were in chronic phase, 01 in accelerated phase and 04 in blast crisis. JAK2V617F mutation was detected in 12 (26.7%) patients; 09 (22.5%) in chronic phase, none in accelerated phase and 03 (75%) in blast crisis. During a mean follow-up of 8 months, 03 patients in chronic phase transformed in blast crisis and 02 into accelerated phase. Overall 08 out of 11 (73%) JAK2V617F positive patients either had advanced disease or showed disease progression. Only 2 of 20 (10%) available patients, negative for the mutation, showed disease progression by transforming into blast crisis (p < 0.001). No statistically significant difference was seen in the age, spleen size, haemoglobin levels, white blood cells and platelets counts in JAK2V617F positive patients. Conclusion: JAK2V617F mutation was detected in 26.7% cases of chronic myeloid leukemia. A significant proportion of them showed early disease progression. (author)

  18. Effects of temperature on disease progression and swimming stamina in Ichthyophonus-infected rainbow trout, Oncorhynchus mykiss (Walbaum).

    Science.gov (United States)

    Kocan, R; Hershberger, P; Sanders, G; Winton, J

    2009-10-01

    Rainbow trout, Oncorhynchus mykiss, were infected with Ichthyophonus sp. and held at 10 degrees C, 15 degrees C and 20 degrees C for 28 days to monitor mortality and disease progression. Infected fish demonstrated more rapid onset of disease, higher parasite load, more severe host tissue reaction and reduced mean-day-to-death at higher temperature. In a second experiment, Ichthyophonus-infected fish were reared at 15 degrees C for 16 weeks then subjected to forced swimming at 10 degrees C, 15 degrees C and 20 degrees C. Stamina improved significantly with increased temperature in uninfected fish; however, this was not observed for infected fish. The difference in performance between infected and uninfected fish became significant at 15 degrees C (P = 0.02) and highly significant at 20 degrees C (P = 0.005). These results have implications for changes in the ecology of fish diseases in the face of global warming and demonstrate the effects of higher temperature on the progression and severity of ichthyophoniasis as well as on swimming stamina, a critical fitness trait of salmonids. This study helps explain field observations showing the recent emergence of clinical ichthyophoniasis in Yukon River Chinook salmon later in their spawning migration when water temperatures were high, as well as the apparent failure of a substantial percentage of infected fish to successfully reach their natal spawning areas.

  19. Effects of temperature on disease progression and swimming stamina in Ichthyophonus-infected rainbow trout, Oncorhynchus mykiss (Walbaum)

    Science.gov (United States)

    Kocan, R.; Hershberger, P.; Sanders, G.; Winton, J.

    2009-01-01

    Rainbow trout, Oncorhynchus mykiss, were infected with Ichthyophonus sp. and held at 10 ??C, 15 ??C and 20 ??C for 28 days to monitor mortality and disease progression. Infected fish demonstrated more rapid onset of disease, higher parasite load, more severe host tissue reaction and reduced mean-day-to-death at higher temperature. In a second experiment, Ichthyophonus-infected fish were reared at 15 ??C for 16 weeks then subjected to forced swimming at 10 ??C, 15 ??C and 20 ??C. Stamina improved significantly with increased temperature in uninfected fish; however, this was not observed for infected fish. The difference in performance between infected and uninfected fish became significant at 15 ??C (P = 0.02) and highly significant at 20 ??C (P = 0.005). These results have implications for changes in the ecology of fish diseases in the face of global warming and demonstrate the effects of higher temperature on the progression and severity of ichthyophoniasis as well as on swimming stamina, a critical fitness trait of salmonids. This study helps explain field observations showing the recent emergence of clinical ichthyophoniasis in Yukon River Chinook salmon later in their spawning migration when water temperatures were high, as well as the apparent failure of a substantial percentage of infected fish to successfully reach their natal spawning areas. ?? 2009 Blackwell Publishing Ltd.

  20. [Research progress in root rot diseases of Chinese herbal medicine and control strategy by antagonistic microorganisms].

    Science.gov (United States)

    Gao, Fen; Ren, Xiao-xia; Wang, Meng-liang; Qin, Xue-mei

    2015-11-01

    In recent years, root rot diseases of Chinese herbal medicine have been posing grave threat to the development of the traditional Chinese medicine industry. This article presents a review on the occurring situation of the root rot disease, including the occurrence of the disease, the diversity of the pathogens, the regional difference in dominant pathogens,and the complexity of symptoms and a survey of the progress in bio-control of the disease using antagonistic microorganisms. The paper also discusses the existing problems and future prospects in the research.

  1. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

    Science.gov (United States)

    Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

    2017-11-01

    Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

  2. Scanning laser Doppler imaging may predict disease progression of localized scleroderma in children and young adults.

    Science.gov (United States)

    Shaw, L J; Shipley, J; Newell, E L; Harris, N; Clinch, J G; Lovell, C R

    2013-07-01

    Localized scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites, but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localized scleroderma. To examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment. A group of 20 individuals had clinical assessment and scanning LDI blood-flow measurements of 32 affected body sites. After a mean follow-up of 8.7 months their clinical outcome was compared with the results of the initial LDI assessment. Eleven out of 15 patients with an assessment of active LDI had progressed clinically, and 16 out of the 17 scans with inactive LDI assessment had not progressed, giving a positive predictive value of 73% and a negative predictive value of 94%. We believe that LDI can be a useful tool in predicting disease progression in localized scleroderma, and it may help clinicians to decide which patients to treat early. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

  3. Factors associated with coronary artery disease progression assessed by serial coronary computed tomography angiography

    International Nuclear Information System (INIS)

    Camargo, Gabriel Cordeiro; Gottlieb, Ilan; Rothstein, Tamara; Derenne, Maria Eduarda; Sabioni, Leticia; Lima, Ronaldo de Souza Leão; Lima, João A. C.

    2017-01-01

    Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01–1.07), interstudy interval (OR 1.03, 95%CI 1.01–1.04), and past PCI (OR 3.66, 95%CI 1.77–7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression. (author)

  4. Factors associated with coronary artery disease progression assessed by serial coronary computed tomography angiography

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, Gabriel Cordeiro; Gottlieb, Ilan, E-mail: ilangottlieb@gmail.com [Casa de Saúde São José, Rio de Janeiro, RJ (Brazil); Rothstein, Tamara; Derenne, Maria Eduarda; Sabioni, Leticia; Lima, Ronaldo de Souza Leão [Centro de Diagnóstico por Imagem CDPI, Rio de Janeiro, RJ (Brazil); Lima, João A. C. [Johns Hopkins University, Baltimore (United States)

    2017-05-15

    Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01–1.07), interstudy interval (OR 1.03, 95%CI 1.01–1.04), and past PCI (OR 3.66, 95%CI 1.77–7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression. (author)

  5. [Progressive pulmonary hypertension in a patient with type 1 Gaucher disease].

    Science.gov (United States)

    Ponomarev, R V; Model, S V; Averbukh, O M; Gavrilov, A M; Galstyan, G M; Lukina, E A

    Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.

  6. Progress Monitoring Change in Children's Social, Emotional, and Behavioral Functioning: Advancing the State of the Science

    Science.gov (United States)

    Owens, Julie Sarno; Evans, Steven W.

    2018-01-01

    The studies in this special series examine the effectiveness of direct behavior ratings (DBRs) for use as a progress monitoring tool. In this article, we comment on the findings of the studies in the context of the broader school-based assessment movement and discuss areas for future inquiry within this line of research.

  7. Cardiac Acceleration at the Onset of Exercise : A Potential Parameter for Monitoring Progress During Physical Training in Sports and Rehabilitation

    NARCIS (Netherlands)

    Hettinga, Florentina J.; Monden, Paul G.; van Meeteren, Nico L. U.; Daanen, Hein A. M.

    There is a need for easy-to-use methods to assess training progress in sports and rehabilitation research. The present review investigated whether cardiac acceleration at the onset of physical exercise (HRonset) can be used as a monitoring variable. The digital databases of Scopus and PubMed were

  8. Cardiac acceleration at the onset of exercise: A potential parameter for monitoring progress during physical training in sports and rehabilitation

    NARCIS (Netherlands)

    Hettinga, F.J.; Monden, P.G.; Meeteren, N.L.U. van; Daanen, H.A.M.

    2014-01-01

    There is a need for easy-to-use methods to assess training progress in sports and rehabilitation research. The present review investigated whether cardiac acceleration at the onset of physical exercise (HRonset) can be used as a monitoring variable. The digital databases of Scopus and PubMed were

  9. Curriculum-Based Measurement of Reading: An Evaluation of Frequentist and Bayesian Methods to Model Progress Monitoring Data

    Science.gov (United States)

    Christ, Theodore J.; Desjardins, Christopher David

    2018-01-01

    Curriculum-Based Measurement of Oral Reading (CBM-R) is often used to monitor student progress and guide educational decisions. Ordinary least squares regression (OLSR) is the most widely used method to estimate the slope, or rate of improvement (ROI), even though published research demonstrates OLSR's lack of validity and reliability, and…

  10. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

    Science.gov (United States)

    Musumeci, Giuseppe; Aiello, Flavia Concetta; Szychlinska, Marta Anna; Di Rosa, Michelino; Castrogiovanni, Paola; Mobasheri, Ali

    2015-01-01

    Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder. PMID:25785564

  11. Does significant renal ablation truly and invariably lead to hyperfiltration and progressive chronic kidney disease?

    Science.gov (United States)

    Wang, Andrew; Sam, Ramin

    2017-06-01

    It is generally believed that significant renal ablation leads to hyperfiltration and eventually progressively worsening chronic kidney disease. The data behind this belief have not been scrutinized intensively. More importantly, the above belief leads many physicians to manage patients differently than they otherwise would manage. Here, we examine the data behind whether hyperfiltration occurs when patients lose kidney mass (by excision or by disease) and whether the hyperfiltration is uniformly injurious.

  12. Building Construction Progress Monitoring Using Unmanned Aerial System (uas), Low-Cost Photogrammetry, and Geographic Information System (gis)

    Science.gov (United States)

    Bognot, J. R.; Candido, C. G.; Blanco, A. C.; Montelibano, J. R. Y.

    2018-05-01

    Monitoring the progress of building's construction is critical in construction management. However, measuring the building construction's progress are still manual, time consuming, error prone, and impose tedious process of analysis leading to delays, additional costings and effort. The main goal of this research is to develop a methodology for building construction progress monitoring based on 3D as-built model of the building from unmanned aerial system (UAS) images, 4D as-planned model (with construction schedule integrated) and, GIS analysis. Monitoring was done by capturing videos of the building with a camera-equipped UAS. Still images were extracted, filtered, bundle-adjusted, and 3D as-built model was generated using open source photogrammetric software. The as-planned model was generated from digitized CAD drawings using GIS. The 3D as-built model was aligned with the 4D as-planned model of building formed from extrusion of building elements, and integration of the construction's planned schedule. The construction progress is visualized via color-coding the building elements in the 3D model. The developed methodology was conducted and applied from the data obtained from an actual construction site. Accuracy in detecting `built' or `not built' building elements ranges from 82-84 % and precision of 50-72 %. Quantified progress in terms of the number of building elements are 21.31% (November 2016), 26.84 % (January 2017) and 44.19 % (March 2017). The results can be used as an input for progress monitoring performance of construction projects and improving related decision-making process.

  13. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression.

    Science.gov (United States)

    Tovo, Pier-Angelo; Calitri, Carmelina; Scolfaro, Carlo; Gabiano, Clara; Garazzino, Silvia

    2016-01-28

    The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

  14. Progress and policy implication of the Insurance Programs for Catastrophic Diseases in China.

    Science.gov (United States)

    Mao, Wenhui; Zhang, Luying; Chen, Wen

    2017-07-01

    The State Council encouraged the involvement of commercial insurance companies (CICs) in the development of the Insurance Program for Catastrophic Diseases (IPCD), yet its implementation has rarely been reported. We collected literature and policy documentation and conducted interviews in 10 cities with innovative IPCD policies to understand the details of the implementation of IPCD. IPCDs are operated at the prefectural level in 14 provinces, while in 4 municipalities and 6 provinces, unified IPCDs have been implemented at higher levels. The contribution level varied from 5% to 10% of total Basic Medical Insurance (BMI) funds or CNY10-35 per beneficiary in 2015. IPCD provides an additional 50% to 70% reimbursement rate for the expenses not covered by BMI with various settings in different locations. Two models of CIC operation of IPCD have been identified according to the financial risks shared by CICs. Either the local department of Human Resources and Social Security or a third party performs assessments of the IPCD operation, service quality, and patients' satisfaction. A number of IPCDs have been observed to use 1% to 5% of the funds as a performance-based payment to the CIC(s). CIC involvement in operating the IPCD raises concerns regarding the security of the information of beneficiaries. Developing appropriate data sharing mechanisms between the local department of Human Resources and Social Security and CICs is still in progress. In conclusion, the IPCD relieves the financial burden on patients by providing further reimbursement, but its benefit package remains limited to the BMI reimbursable list. CICs play an important role in monitoring and supervising health service provision, yet their capacity for actuarial services or risk control is underdeveloped. Copyright © 2017 John Wiley & Sons, Ltd.

  15. The utility of cerebral blood flow imaging in patients with the unique syndrome of progressive dementia with motor neuron disease

    International Nuclear Information System (INIS)

    Ohnishi, T.; Hoshi, H.; Jinnouchi, S.; Nagamachi, S.; Watanabe, K.; Mituyama, Y.

    1990-01-01

    Two patients presenting with progressive dementia coupled with motor neuron disease underwent brain SPECT using N-isopropyl-p iodine-123-iodoamphetamine [( 123 I]IMP). The characteristic clinical features of progressive dementia and motor neuron disease were noted. IMP SPECT also revealed reduced uptake in the bilateral frontal and temporal regions, with no reduction of uptake in the parietal, parietal-occipital regions. We conclude that IMP SPECT has potential for the evaluation of progressive dementia with motor neuron disease

  16. Monitoring of the periodontal disease using digital image analyses

    International Nuclear Information System (INIS)

    Taba Junior, Mario.

    1995-01-01

    The radiographs play an important role in the diagnosis and management of periodontal disease although the most appropriate form of assessment vary. The great technologic advance and the easily accessible systems of digital image analyses, specify digitized radiographs, improve the diagnostic power. The studied group was 29 adults (14 female and 15 male) ranging in age from 18 to 45 years. They all had evidence of alveolar bone loss and established periodontitis. They were studied, without treatment, over a six month period with four posterior standardized vertical bite wings radiographs, electronic probing of attachment loss, and bacteriological and temperature analysis of periodontal pocket. The aim of this investigation was to determine the relationship between the loss of radiographic crestal bone height and probing attachment loss in digitized radiographs and show a standardization method for periodontal radiographs. Radiographic and probing attachment change at all sites, dichotomously classified as to not changing or loosing indicated 20.42% of sites were loosing by measurement of radiographic change and 5.29% were loosing by measurement of attachment change. There was concordance between the presence or absence of probing attachment loss and bone loss in 72% to 86% depending on the area. The results, admitting methodological limitations, indicate that when these two methods for the assessment of progressive periodontitis were used they represents measure degrees of different features of periodontitis and that the period of periodontal disease activity was detected in the either the soft tissue attachment or bone. (author)

  17. Impact of HIV Type 1 DNA Levels on Spontaneous Disease Progression: A Meta-Analysis

    DEFF Research Database (Denmark)

    Tsiara, Chrissa G; Nikolopoulos, Georgios K; Bagos, Pantelis G

    2012-01-01

    Abstract Several studies have reported the prognostic strength of HIV-1 DNA with variable results however. The aims of the current study were to estimate more accurately the ability of HIV-1 DNA to predict progression of HIV-1 disease toward acquired immunodeficiency syndrome (AIDS) or death...... of primary studies indicated that HIV-1 DNA was a significantly better predictor than HIV-1 RNA of either AIDS alone (ratio of RRs=1.47, 95% CI: 1.05-2.07) or of combined (AIDS or death) progression outcomes (ratio of RRs=1.51, 95% CI: 1.11-2.05). HIV-1 DNA is a strong predictor of HIV-1 disease progression...

  18. Effect of blood pressure lowering on markers of kidney disease progression.

    Science.gov (United States)

    Udani, Suneel M; Koyner, Jay L

    2009-10-01

    Hypertension remains a common comorbidity and cause of chronic kidney disease (CKD). As the number of patients with CKD grows, so does the need to identify modifiable risk factors for CKD progression. Data on slowing progression of CKD or preventing end-stage renal disease with aggressive blood pressure control have not yielded definitive conclusions regarding ideal blood pressure targets. Shifting the focus of antihypertensive therapy to alternative markers of end-organ damage, specifically proteinuria, has yielded some promise in preventing the progression of CKD. Nevertheless, proteinuria and decline in estimated GFR may represent an irreversible degree of injury to the kidney that limits the impact of any therapy. The identification and use of novel markers of kidney injury to assess the impact of antihyper-tensive therapy may yield clearer direction with regard to optimal management of hypertension in the setting of CKD.

  19. Association Between Breast Cancer Disease Progression and Workplace Productivity in the United States.

    Science.gov (United States)

    Yin, Wesley; Horblyuk, Ruslan; Perkins, Julia Jane; Sison, Steve; Smith, Greg; Snider, Julia Thornton; Wu, Yanyu; Philipson, Tomas J

    2017-02-01

    Determine workplace productivity losses attributable to breast cancer progression. Longitudinal analysis linking 2005 to 2012 medical and pharmacy claims and workplace absence data in the US patients were commercially insured women aged 18 to 64 diagnosed with breast cancer. Productivity was measured as employment status and total quarterly workplace hours missed, and valued using average US wages. Six thousand four hundred and nine women were included. Breast cancer progression was associated with a lower probability of employment (hazard ratio [HR] = 0.65, P work was $24,166 for non-metastatic and $30,666 for metastatic patients. Thus, progression to metastatic disease is associated with an additional $6500 in lost work time (P < 0.05), or 14% of average US wages. Breast cancer progression leads to diminished likelihood of employment, increased workplace hours missed, and increased cost burden.

  20. Pervasive mobile healthcare systems for chronic disease monitoring.

    Science.gov (United States)

    Huzooree, Geshwaree; Kumar Khedo, Kavi; Joonas, Noorjehan

    2017-05-01

    Pervasive mobile healthcare system has the potential to improve healthcare and the quality of life of chronic disease patients through continuous monitoring. Recently, many articles related to pervasive mobile healthcare system focusing on health monitoring using wireless technologies have been published. The main aim of this review is to evaluate the state-of-the-art pervasive mobile healthcare systems to identify major technical requirements and design challenges associated with the realization of a pervasive mobile healthcare system. A systematic literature review was conducted over IEEE Xplore Digital Library to evaluate 20 pervasive mobile healthcare systems out of 683 articles from 2011 to 2016. The classification of the pervasive mobile healthcare systems and other important factors are discussed. Potential opportunities and challenges are pointed out for the further deployment of effective pervasive mobile healthcare systems. This article helps researchers in health informatics to have a holistic view toward understanding pervasive mobile healthcare systems and points out new technological trends and design challenges that researchers have to consider when designing such systems for better adoption, usability, and seamless integration.

  1. Response monitoring in de novo patients with Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Rita Willemssen

    Full Text Available BACKGROUND: Parkinson's disease (PD is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD". METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD.

  2. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study

    DEFF Research Database (Denmark)

    Viard, Jean-Paul; Souberbielle, Jean-Claude; Kirk, Ole

    2011-01-01

    BACKGROUND:: We examined the association between vitamin D [25(OH)D] level and disease progression in HIV infection. METHODS:: Within the EuroSIDA study, 2000 persons were randomly selected for 25(OH)D measurement in stored plasma samples closest to study entry. 25(OH)D results were stratified...

  3. Effect of Sex Hormones on Progression of Diabetic Renal Disease in ...

    African Journals Online (AJOL)

    Effect of Sex Hormones on Progression of Diabetic Renal Disease in Experimental Model of Streptozotocin Induced Diabetic Rats. ... into five groups 8 rats each, normal control, diabetic, gonadectomized diabetic, 17 beta estradiol is given to female and testosterone propionate to male diabetic and gonadectomized diabetic.

  4. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    NARCIS (Netherlands)

    Sluimer, J.D.; van der Flier, W.M.; Karas, G.B.; van Schijndel, R.; Barnes, J.; Boyes, R.G.; Cover, K.S.; Olabarriaga, S.D.; Fox, N.C.; Scheltens, P.; Vrenken, H.; Barkhof, F.

    2009-01-01

    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 +/- 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate

  5. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease

    NARCIS (Netherlands)

    Krenning, Guido; Dankers, Patricia Y. W.; Drouven, Johannes W.; Waanders, Femke; Franssen, Casper F. M.; van Luyn, Marja J. A.; Harmsen, Martin C.; Popa, Eliane R.

    Krenning G, Dankers PY, Drouven JW, Waanders F, Franssen CF, van Luyn MJ, Harmsen MC, Popa ER. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease. Am J Physiol Renal Physiol 296: F1314-F1322, 2009. First published April 1, 2009; doi:

  6. Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Stefano Zanigni

    2016-01-01

    Conclusion: Although several quantitative brain MR markers provided high diagnostic accuracy in differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, the morphometric assessment of midbrain area is the best single diagnostic marker and should be routinely included in the neuroradiological work-up of parkinsonian patients.

  7. Correction to: Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

    Science.gov (United States)

    Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

    2018-04-10

    The article "Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event," written by Joseph R. Berger, Vineeta Malik, Stuart Lacey, Paul Brunetta, and Patricia B. Lehane 3 , was originally published electronically on the publisher's internet portal (currently SpringerLink).

  8. Disease impact in chronic progressive external ophthalmoplegia: more than meets the eye

    NARCIS (Netherlands)

    Smits, B.W.; Fermont, J.; Delnooz, C.C.S.; Kalkman, J.S.; Bleijenberg, G.; Engelen, B.G.M. van

    2011-01-01

    We determined the extent of disease impact in 28 patients with genetically confirmed chronic progressive external ophthalmoplegia (CPEO) and compared the outcomes to those of matched myotonic dystrophy type I patients. CPEO patients reported a high frequency of severe fatigue (67.9%), pain (96.2%),

  9. Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

    NARCIS (Netherlands)

    Veenstra, J.; Krol, A.; van Praag, R. M.; Frissen, P. H.; Schellekens, P. T.; Lange, J. M.; Coutinho, R. A.; van der Meer, J. T.

    1995-01-01

    OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied.

  10. CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients

    DEFF Research Database (Denmark)

    Fløyel, Tina; Brorsson, Caroline; Nielsen, Lotte B

    2014-01-01

    expression and increased insulin secretion. Additionally, islets from Ctsh(-/-) mice contained less insulin than islets from WT mice. Importantly, the TT genotype was associated with higher daily insulin dose and faster disease progression in newly diagnosed T1D patients, indicating agreement between...

  11. Untreated periodontal disease in Indonesian adolescents : Subgingival microbiota in relation to experienced progression of periodontitis

    NARCIS (Netherlands)

    Timmerman, MF; Van der Weijden, GA; Arief, EM; Armand, S; Abbas, F; Winkel, EG; Van Winkelhoff, AJ; Van der Velden, U

    Background/aims: In an Indonesian population deprived of regular dental care, the experienced progression of disease between baseline (1987) and follow-up (1994) was investigated in relation to the composition of the subgingival microbiota at follow-up. At baseline the age ranged from 15 to 25

  12. Brain Substrates of Learning and Retention in Mild Cognitive Impairment Diagnosis and Progression to Alzheimer's Disease

    Science.gov (United States)

    Chang, Yu-Ling; Bondi, Mark W.; Fennema-Notestine, Christine; McEvoy, Linda K.; Hagler, Donald J., Jr.; Jacobson, Mark W.; Dale, Anders M.

    2010-01-01

    Understanding the underlying qualitative features of memory deficits in mild cognitive impairment (MCI) can provide critical information for early detection of Alzheimer's disease (AD). This study sought to investigate the utility of both learning and retention measures in (a) the diagnosis of MCI, (b) predicting progression to AD, and (c)…

  13. Non-monotonic reorganization of brain networks with Alzheimer’s disease progression

    Directory of Open Access Journals (Sweden)

    Hyoungkyu eKim

    2015-06-01

    Full Text Available Background: Identification of stage-specific changes in brain network of patients with Alzheimer’s disease (AD is critical for rationally designed therapeutics that delays the progression of the disease. However, pathological neural processes and their resulting changes in brain network topology with disease progression are not clearly known. Methods: The current study was designed to investigate the alterations in network topology of resting state fMRI among patients in three different clinical dementia rating (CDR groups (i.e., CDR = 0.5, 1, 2 and amnestic mild cognitive impairment (aMCI and age-matched healthy subject groups. We constructed cost networks from these 5 groups and analyzed their network properties using graph theoretical measures.Results: The topological properties of AD brain networks differed in a non-monotonic, stage-specific manner. Interestingly, local and global efficiency and betweenness of the network were rather higher in the aMCI and AD (CDR 1 groups than those of prior stage groups. The number, location, and structure of rich-clubs changed dynamically as the disease progressed.Conclusions: The alterations in network topology of the brain are quite dynamic with AD progression, and these dynamic changes in network patterns should be considered meticulously for efficient therapeutic interventions of AD.

  14. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

    2011-01-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  15. Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease.

    Science.gov (United States)

    Cholerton, Brenna; Johnson, Catherine O; Fish, Brian; Quinn, Joseph F; Chung, Kathryn A; Peterson-Hiller, Amie L; Rosenthal, Liana S; Dawson, Ted M; Albert, Marilyn S; Hu, Shu-Ching; Mata, Ignacio F; Leverenz, James B; Poston, Kathleen L; Montine, Thomas J; Zabetian, Cyrus P; Edwards, Karen L

    2018-05-01

    Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Role of Diet and Nutritional Supplements in Parkinson’s Disease Progression

    Directory of Open Access Journals (Sweden)

    Laurie K. Mischley

    2017-01-01

    Full Text Available Objectives. The goal of this study is to describe modifiable lifestyle variables associated with reduced rate of Parkinson’s disease (PD progression. Methods. The patient-reported outcomes in PD (PRO-PD were used as the primary outcome measure, and a food frequency questionnaire (FFQ was used to assess dietary intake. In this cross-sectional analysis, regression analysis was performed on baseline data to identify the nutritional and pharmacological interventions associated with the rate of PD progression. All analyses were adjusted for age, gender, and years since diagnosis. Results. 1053 individuals with self-reported idiopathic PD were available for analysis. Foods associated with the reduced rate of PD progression included fresh vegetables, fresh fruit, nuts and seeds, nonfried fish, olive oil, wine, coconut oil, fresh herbs, and spices (P<0.05. Foods associated with more rapid PD progression include canned fruits and vegetables, diet and nondiet soda, fried foods, beef, ice cream, yogurt, and cheese (P<0.05. Nutritional supplements coenzyme Q10 and fish oil were associated with reduced PD progression (P=0.026 and P=0.019, resp., and iron supplementation was associated with faster progression (P=0.022. Discussion. These are the first data to provide evidence that targeted nutrition is associated with the rate of PD progression.

  17. Unveiling clusters of RNA transcript pairs associated with markers of Alzheimer's disease progression.

    Directory of Open Access Journals (Sweden)

    Ahmed Shamsul Arefin

    Full Text Available BACKGROUND: One primary goal of transcriptomic studies is identifying gene expression patterns correlating with disease progression. This is usually achieved by considering transcripts that independently pass an arbitrary threshold (e.g. p<0.05. In diseases involving severe perturbations of multiple molecular systems, such as Alzheimer's disease (AD, this univariate approach often results in a large list of seemingly unrelated transcripts. We utilised a powerful multivariate clustering approach to identify clusters of RNA biomarkers strongly associated with markers of AD progression. We discuss the value of considering pairs of transcripts which, in contrast to individual transcripts, helps avoid natural human transcriptome variation that can overshadow disease-related changes. METHODOLOGY/PRINCIPAL FINDINGS: We re-analysed a dataset of hippocampal transcript levels in nine controls and 22 patients with varying degrees of AD. A large-scale clustering approach determined groups of transcript probe sets that correlate strongly with measures of AD progression, including both clinical and neuropathological measures and quantifiers of the characteristic transcriptome shift from control to severe AD. This enabled identification of restricted groups of highly correlated probe sets from an initial list of 1,372 previously published by our group. We repeated this analysis on an expanded dataset that included all pair-wise combinations of the 1,372 probe sets. As clustering of this massive dataset is unfeasible using standard computational tools, we adapted and re-implemented a clustering algorithm that uses external memory algorithmic approach. This identified various pairs that strongly correlated with markers of AD progression and highlighted important biological pathways potentially involved in AD pathogenesis. CONCLUSIONS/SIGNIFICANCE: Our analyses demonstrate that, although there exists a relatively large molecular signature of AD progression, only

  18. Site-level progression of periodontal disease during a follow-up period

    Science.gov (United States)

    Morozumi, Toshiya; Nakagawa, Taneaki; Sugaya, Tsutomu; Kawanami, Masamitsu; Suzuki, Fumihiko; Takahashi, Keiso; Abe, Yuzo; Sato, Soh; Makino-Oi, Asako; Saito, Atsushi; Takano, Satomi; Minabe, Masato; Nakayama, Yohei; Ogata, Yorimasa; Kobayashi, Hiroaki; Izumi, Yuichi; Sugano, Naoyuki; Ito, Koichi; Sekino, Satoshi; Numabe, Yukihiro; Fukaya, Chie; Yoshinari, Nobuo; Fukuda, Mitsuo; Noguchi, Toshihide; Kono, Tomoo; Umeda, Makoto; Fujise, Osamu; Nishimura, Fusanori; Yoshimura, Atsutoshi; Hara, Yoshitaka; Nakamura, Toshiaki; Noguchi, Kazuyuki; Kakuta, Erika; Hanada, Nobuhiro; Takashiba, Shogo; Amitani, Yasuharu; Yoshie, Hiromasa

    2017-01-01

    Periodontal disease is assessed and its progression is determined via observations on a site-by-site basis. Periodontal data are complex and structured in multiple levels; thus, applying a summary statistical approach (i.e., the mean) for site-level evaluations results in loss of information. Previous studies have shown the availability of mixed effects modeling. However, clinically beneficial information on the progression of periodontal disease during the follow-up period is not available. We conducted a multicenter prospective cohort study. Using mixed effects modeling, we analyzed 18,834 sites distributed on 3,139 teeth in 124 patients, and data were collected 5 times over a 24-month follow-up period. The change in the clinical attachment level (CAL) was used as the outcome variable. The CAL at baseline was an important determinant of the CAL changes, which varied widely according to the tooth surface. The salivary levels of periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were affected by CAL progression. “Linear”- and “burst”-type patterns of CAL progression occurred simultaneously within the same patient. More than half of the teeth that presented burst-type progression sites also presented linear-type progression sites, and most of the progressions were of the linear type. Maxillary premolars and anterior teeth tended to show burst-type progression. The parameters identified in this study may guide practitioners in determining the type and extent of treatment needed at the site and patient levels. In addition, these results show that prior hypotheses concerning "burst" and "linear" theories are not valid. PMID:29206238

  19. Role for transforming growth factor-beta1 in alport renal disease progression.

    Science.gov (United States)

    Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D

    1999-11-01

    Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.

  20. Progress and challenges in the prevention and control of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Cai, Jingjing; Zhang, Xiao-Jing; Li, Hongliang

    2018-05-30

    Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets. © 2018 Wiley Periodicals, Inc.

  1. Cardiac acceleration at the onset of exercise: a potential parameter for monitoring progress during physical training in sports and rehabilitation.

    Science.gov (United States)

    Hettinga, Florentina J; Monden, Paul G; van Meeteren, Nico L U; Daanen, Hein A M

    2014-05-01

    There is a need for easy-to-use methods to assess training progress in sports and rehabilitation research. The present review investigated whether cardiac acceleration at the onset of physical exercise (HRonset) can be used as a monitoring variable. The digital databases of Scopus and PubMed were searched to retrieve studies investigating HRonset. In total 652 studies were retrieved. These articles were then classified as having emphasis on HRonset in a sports or rehabilitation setting, which resulted in 8 of 112 studies with a sports application and 6 of 68 studies with a rehabilitation application that met inclusion criteria. Two co-existing mechanisms underlie HRonset: feedforward (central command) and feedback (mechanoreflex, metaboreflex, baroreflex) control. A number of studies investigated HRonset during the first few seconds of exercise (HRonsetshort), in which central command and the mechanoreflex determine vagal withdrawal, the major mechanism by which heart rate (HR) increases. In subsequent sports and rehabilitation studies, interest focused on HRonset during dynamic exercise over a longer period of time (HRonsetlong). Central command, mechanoreflexes, baroreflexes, and possibly metaboreflexes contribute to HRonset during the first seconds and minutes of exercise, which in turn leads to further vagal withdrawal and an increase in sympathetic activity. HRonset has been described as the increase in HR compared with resting state (delta HR) or by exponential modeling, with measurement intervals ranging from 0-4 s up to 2 min. Delta HR was used to evaluate HRonsetshort over the first 4 s of exercise, as well as for analyzing HRonsetlong. In exponential modeling, the HR response to dynamic exercise is biphasic, consisting of fast (parasympathetic, 0-10 s) and slow (sympathetic, 1-4 min) components. Although available studies differed largely in measurement protocols, cross-sectional and longitudinal training studies showed that studies analyzing HRonset

  2. Progress in using real-time GPS for seismic monitoring of the Cascadia megathrust

    Science.gov (United States)

    Szeliga, W. M.; Melbourne, T. I.; Santillan, V. M.; Scrivner, C.; Webb, F.

    2014-12-01

    We report on progress in our development of a comprehensive real-time GPS-based seismic monitoring system for the Cascadia subduction zone. This system is based on 1 Hz point position estimates computed in the ITRF08 reference frame. Convergence from phase and range observables to point position estimates is accelerated using a Kalman filter based, on-line stream editor. Positions are estimated using a short-arc approach and algorithms from JPL's GIPSY-OASIS software with satellite clock and orbit products from the International GNSS Service (IGS). The resulting positions show typical RMS scatter of 2.5 cm in the horizontal and 5 cm in the vertical with latencies below 2 seconds. To facilitate the use of these point position streams for applications such as seismic monitoring, we broadcast real-time positions and covariances using custom-built streaming software. This software is capable of buffering 24-hour streams for hundreds of stations and providing them through a REST-ful web interface. To demonstrate the power of this approach, we have developed a Java-based front-end that provides a real-time visual display of time-series, vector displacement, and contoured peak ground displacement. We have also implemented continuous estimation of finite fault slip along the Cascadia megathrust using an NIF approach. The resulting continuous slip distributions are combined with pre-computed tsunami Green's functions to generate real-time tsunami run-up estimates for the entire Cascadia coastal margin. This Java-based front-end is available for download through the PANGA website. We currently analyze 80 PBO and PANGA stations along the Cascadia margin and are gearing up to process all 400+ real-time stations operating in the Pacific Northwest, many of which are currently telemetered in real-time to CWU. These will serve as milestones towards our over-arching goal of extending our processing to include all of the available real-time streams from the Pacific rim. In addition

  3. The effect of cigarette smoking, tea, and coffee consumption on the progression of Parkinson's disease.

    Science.gov (United States)

    Kandinov, Boris; Giladi, Nir; Korczyn, Amos D

    2007-05-01

    Previous epidemiological studies found a negative association between cigarette smoking, tea or coffee drinking with the occurrence of Parkinson's disease (PD). However, it is unknown how these factors affect the rate of progression of the disease. A retrospective study was conducted among 278 consecutive PD patients. Data on smoking and coffee or tea consumption were obtained through direct or proxy interviews, and the time from onset of motor symptoms until reaching Hoehn & Yahr (H&Y) stage 3 was retrieved from the case records. Cox proportional hazards model and Kaplan-Meyer model were used to estimate whether the dependent variables (smoking, drinking coffee or tea) affect the rate of progression of the disease, which was measured by the time it took patients to reach H&Y stage 3. We found that disease progression was not affected by cigarette smoking, tea or coffee consumption. The present study suggests that these variables do not have a disease modifying effect in already diagnosed PD patients.

  4. Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease progression

    DEFF Research Database (Denmark)

    Tolstrup, Martin; Laursen, Alex Lund; Gerstoft, J.

    2006-01-01

    on the delayed disease status. However, the results demonstrate a high incidence of a single amino acid polymorphism (cysteine 138) in HIV-1 Nef. The allelic frequency of cysteine 138 between the delayed disease progression group and the progressor group was found to be statistically significant (P = 0.......0139). The phylogeny of isolates was investigated and the variants harbouring the cysteine 138 mutation clustered independently. CONCLUSION: The present study describes a viral genetic polymorphism related to AIDS disease progression. The polymorphism (cysteine 138) has previously been reported to confer decreased...... viral replication (Premkumar DR, et al. AIDS Res Hum Retroviruses 1996; 12(4): 337-45). A sequence database search for comparative mutations revealed a high frequency of cysteine 138 in patients with reported SP AIDS...

  5. Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease progression

    DEFF Research Database (Denmark)

    Tolstrup, Martin; Laursen, Alex Lund; Gerstoft, J.

    2006-01-01

    .0139). The phylogeny of isolates was investigated and the variants harbouring the cysteine 138 mutation clustered independently. CONCLUSION: The present study describes a viral genetic polymorphism related to AIDS disease progression. The polymorphism (cysteine 138) has previously been reported to confer decreased......-1 isolates from patients in a long-term non-progressor (LTNP) cohort and a slow-progressor (SP) cohort (n = 11) was analysed and compared with isolates from a control patient group of progressors (n = 18). Most of the patients with delayed disease progression had extensive medical records, providing...... an insight into the LTNP disease profile and allowing for the stratification of patients based on their CD4 cell decline. RESULTS: In sequences from nine patients, most of the functional domains of HIV-1 Nef appeared intact, and no major deletions were observed to possibly account for an effect...

  6. An Unrecognized Rash Progressing to Lyme Carditis: Important Features and Recommendations Regarding Lyme Disease.

    Science.gov (United States)

    Lee, Shawn; Singla, Montish

    2016-01-01

    We present a case report of 46-year-old man with no medical history, who complained of extreme fatigue, near-syncope, and palpitations. He initially presented in complete heart block. A transvenous pacemaker was placed in the emergency department, and he was started empirically on Ceftriaxone for Lyme disease. He was admitted and over the course of the next few days, his rhythm regressed to Mobitz type I first-degree atrioventricular block and then to normal sinus rhythm. This case report highlights some important features regarding Lyme carditis, a rare presentation of early disseminated Lyme disease (seen in a few weeks to months after the initial tick bite). In 25%-30% of patients, the characteristic targetoid rash may not be seen, a likely culprit of the disease not being detected early and progressing to disseminated disease. The most common cardiac complaint of Lyme disease is palpitations, occurring in 6.6% of patients, which may not accurately reflect progression into disseminated Lyme disease because it is a nonspecific finding. Conduction abnormality, occurring in 1.8% of patients, is a more specific finding of Borrelia invading cardiac tissue. Finally, this case report highlights a recommendation that patients with confirmed Lyme disease or those presenting with cardiac abnormalities or symptoms who have an atypical profile for a cardiac event should be screened with a 12-lead electrocardiogram, Lyme serology, and be considered for antibiotic therapy with the possibility of temporary pacing.

  7. Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

    Science.gov (United States)

    Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S; Rudel, Rebecca K; Gomez-Isla, Teresa; Blacker, Deborah; Hyman, Bradley T; Locascio, Joseph J; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A; Rentz, Dorene M

    2014-12-01

    To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p factor score predicted higher hazard (HR = 1.3 for one SD increase, p = 0.01). No other predictors were significant in adjusted analyses. Using diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Voltage-Gated Potassium Channel Antibodies in Slow-Progression Motor Neuron Disease.

    Science.gov (United States)

    Godani, Massimiliano; Zoccarato, Marco; Beronio, Alessandro; Zuliani, Luigi; Benedetti, Luana; Giometto, Bruno; Del Sette, Massimo; Raggio, Elisa; Baldi, Roberta; Vincent, Angela

    2017-01-01

    The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression. © 2016 S. Karger AG, Basel.

  9. Progressive outer retinal necrosis in the era of highly active antiretroviral therapy: successful management with intravitreal injections and monitoring with quantitative PCR.

    Science.gov (United States)

    Yin, Philip D; Kurup, Shree K; Fischer, Steven H; Rhee, Henry H; Byrnes, Gordon A; Levy-Clarke, Grace A; Buggage, Ronald R; Nussenblatt, Robert B; Mican, JoAnn M; Wright, Mary E

    2007-03-01

    Progressive outer retinal necrosis (PORN) is an ocular disease in individuals with AIDS and is associated with substantial morbidity. The optimal management of PORN and its clinical course in the HAART era is unclear. We report a case of successfully managed PORN that provides insight into the monitoring and treatment of this disease. Intravitreal injections and intravenous therapy targeted towards varicella zoster virus (VZV) were used to treat PORN. HAART was initiated for HIV-1 therapy. Serial PCR for VZV was performed on aqueous humor to monitor the clinical course. The presence of VZV DNA from aqueous humor correlated with clinical exacerbations of disease. Initiation of twice weekly intravitreal injections with dual antiviral drugs appeared to be an important therapeutic intervention that resulted in remission of PORN. Secondary prophylaxis against VZV was successfully withdrawn after HAART induced partial immune recovery. In addition to aggressive therapy with intravitreal injections, HAART and quantitative measurements of VZV DNA from aqueous humor have important roles in the management of PORN. A multidisciplinary approach involving specialists in infectious diseases, ophthalmology, and clinical microbiology will improve the chances for successful long-term outcomes.

  10. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  11. Validating a proxy for disease progression in metastatic cancer patients using prescribing and dispensing data.

    Science.gov (United States)

    Joshi, Vikram; Adelstein, Barbara-Ann; Schaffer, Andrea; Srasuebkul, Preeyaporn; Dobbins, Timothy; Pearson, Sallie-Anne

    2017-10-01

    Routine data collections are used increasingly to examine outcomes of real-world cancer drug use. These datasets lack clinical details about important endpoints such as disease progression. To validate a proxy for disease progression in metastatic cancer patients using prescribing and dispensing claims. We used data from a cohort study of patients undergoing chemotherapy who provided informed consent to the collection of cancer-treatment data from medical records and linkage to pharmaceutical claims. We derived proxy decision rules based on changes to drug treatment in prescription histories (n = 36 patients) and validated the proxy in prescribing data (n = 62 patients). We adapted the decision rules and validated the proxy in dispensing data (n = 109). Our gold standard was disease progression ascertained in patient medical records. Individual progression episodes were the unit of analysis for sensitivity and Positive Predictive Value (PPV) calculations and specificity and Negative Predictive Value (NPV) were calculated at the patient level. The sensitivity of our proxy in prescribing data was 74.3% (95% Confidence Interval (CI), 55.6-86.6%) and PPV 61.2% (95% CI, 45.0-75.3%); specificity and NPV were 87.8% (95% CI, 73.8-95.9%) and 100% (95% CI, 90.3-100%), respectively. In dispensing data, the sensitivity of our proxy was 64% (95% CI, 55.0-77.0%) and PPV 56.0% (95% CI, 43.0-69.0%); specificity and NPV were 81% (95% CI, 70.05-89.0%) and 91.0% (95% CI, 82.0-97.0%), respectively. Our proxy overestimated episodes of disease progression. The proxy's performance is likely to improve if the date of prescribing is used instead of date of dispensing in claims data and by incorporating medical service claims (such as imaging prior to drug changes) in the algorithm. Our proxy is not sufficiently robust for use in real world comparative effectiveness research for cancer medicines. © 2016 John Wiley & Sons Australia, Ltd.

  12. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  13. Retrospective analysis of factors affecting the progression of Chronic Renal Failure in Adult Polycystic Kidney Disease

    International Nuclear Information System (INIS)

    Ahmed, E.R.; Tashkandi, Muhammed A.; Nahrir, S.; Maulana, A.

    2006-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the commonest congenital cystic renal disease. Factors such as hypertension, urinary tract infection, hematuria and proteinuria may effect the progression to chronic renal failure in ADPKD patients. Therapeutic interventions, such as the use of angiotensin converting enzyme inhibitors (ACEI) or diet modification, may impact the natural progression of the disease. We aim in this study to review a registry of ADPKD patients in order to compare the slow and fast progressors and identify possible predictors of progression and interventions that slow the progression of this disease. Sheffield Kidney Institute (SKI), one of the largest kidney institutes in Northern Europe, has registered a large number of ADPKD patients since 1981. SKI's computer network contains a wide range of information on these patients. We selected 94 adult polycystic patients from the SKI for retrospective analysis of factors affecting progression to chronic renal failure. Patients who doubled their s. creatinine in 3 6 months were considered fast progressors (FP), while those who doubled their s. creatinine in > 36 months were regarded as slow progressors (SP). There 70 patients in the FP group and 24 patients in the SP group. A third group of 137 patients consisted of non-progressors (NP) who ha d stable s. creatinine levels during the same period. We found that the incidence of hypertension, UTI, macroscopic and microscopic hematuria, and overt proteinuria in the FP group was higher than in SP and NP groups. Modification of some factors, such as hypertension and UTI, may decrease the rate of the deterioration of renal function. (author)

  14. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 1. Technical Report # 0919

    Science.gov (United States)

    Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grade 1. These measures, available as part of easyCBM [TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from schools…

  15. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Kindergarten. Technical Report # 0921

    Science.gov (United States)

    Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in kindergarten. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from…

  16. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 3. Technical Report # 09-02

    Science.gov (United States)

    Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  17. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 5. Technical Report # 09-01

    Science.gov (United States)

    Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  18. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 2. Technical Report # 0920

    Science.gov (United States)

    Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  19. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 7. Technical Report 0908

    Science.gov (United States)

    Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  20. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 4. Technical Report # 09-03

    Science.gov (United States)

    Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  1. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 8. Technical Report # 09-04

    Science.gov (United States)

    Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  2. Progress of the relationship between serum uric acid and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Yang FU

    2018-04-01

    Full Text Available Serum uric acid (sUA, a natural antioxidant in human body, has been found to be related to the occurrence and development of various neurodegenerative diseases in recent years, including Parkinson's disease (PD, multiple system atrophy (MSA, Alzheimer's disease (AD and amyotrophic lateral sclerosis (ALS. Increasing of sUA level has been found to reduce the incidence of PD and ALS, but the relationship between sUA and AD, MSA remains largely unknown. The in vitro studies and animal experiments revealed that sUA can enhance the antioxidant capacity of neurons and delay neurodegeneration and apoptosis. This paper mainly reviews the progress in epidemiological and basic studies of the relationship between sUA and neurodegenerative diseases in recent years, and aims to provide a reference for future novel prevention and treatment strategies for neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2018.03.010

  3. Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

    Science.gov (United States)

    Ishibashi, Hidetoshi; Minakawa, Eiko N.; Motohashi, Hideyuki H.; Takayama, Osamu; Popiel, H. Akiko; Puentes, Sandra; Owari, Kensuke; Nakatani, Terumi; Nogami, Naotake; Yamamoto, Kazuhiro; Yonekawa, Takahiro; Tanaka, Yoko; Fujita, Naoko; Suzuki, Hikaru; Aizawa, Shu; Nagano, Seiichi; Yamada, Daisuke; Wada, Keiji; Kohsaka, Shinichi

    2017-01-01

    Abstract Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases. PMID:28374014

  4. Phenotypic Progression of Stargardt Disease in a Large Consanguineous Tunisian Family Harboring New ABCA4 Mutations

    Directory of Open Access Journals (Sweden)

    Yousra Falfoul

    2018-01-01

    Full Text Available To assess the progression of Stargardt (STGD disease over nine years in two branches of a large consanguineous Tunisian family. Initially, different phenotypes were observed with clinical intra- and interfamilial variations. At presentation, four different retinal phenotypes were observed. In phenotype 1, bull’s eye maculopathy and slight alteration of photopic responses in full-field electroretinography were observed in the youngest child. In phenotype 2, macular atrophy and yellow white were observed in two brothers. In phenotype 3, diffuse macular, peripapillary, and peripheral RPE atrophy and hyperfluorescent dots were observed in two sisters. In phenotype 4, Stargardt disease-fundus flavimaculatus phenotype was observed in two cousins with later age of onset. After a progression of 9 years, all seven patients displayed the same phenotype 3 with advanced stage STGD and diffuse atrophy. WES and MLPA identified two ABCA4 mutations M1: c.[(?_4635_(5714+?dup; (?_6148_(6479_+? del] and M2: c.[2041C>T], p.[R681∗]. In one branch, the three affected patients had M1/M1 causal mutations and in the other branch the two affected patients had M1/M2 causal mutations. After 9-year follow-up, all patients showed the same phenotypic evolution, confirming the progressive nature of the disease. Genetic variations in the two branches made no difference to similar end-stage disease.

  5. Chronic Progressive Neurodegeneration in a transgenic mouse model of Prion disease

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2016-11-01

    Full Text Available Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic protein without accompanying neurodegeneration pattern. The lack of a comprehensive model hinders the efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice, mimicking for genetic Creutzfeldt-Jacob disease as compared to age matched wild type mice. Mice exhibited a neurodegenerative process indicated by progressive reduction in cortical neurons and synapses, starting at age of 4-6 months, in accordance with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with progressive neurological disease, indicating these mice can serve as a model for neurodegenerative diseases.

  6. View of God as benevolent and forgiving or punishing and judgmental predicts HIV disease progression.

    Science.gov (United States)

    Ironson, Gail; Stuetzle, Rick; Ironson, Dale; Balbin, Elizabeth; Kremer, Heidemarie; George, Annie; Schneiderman, Neil; Fletcher, Mary Ann

    2011-12-01

    This study assessed the predictive relationship between View of God beliefs and change in CD4-cell and Viral Load (VL) in HIV positive people over an extended period. A diverse sample of HIVseropositive participants (N = 101) undergoing comprehensive psychological assessment and blood draws over the course of 4 years completed the View of God Inventory with subscales measuring Positive View (benevolent/forgiving) and Negative View of God (harsh/judgmental/punishing). Adjusting for initial disease status, age, gender, ethnicity, education, and antiretroviral medication (at every 6-month visit), a Positive View of God predicted significantly slower disease-progression (better preservation of CD4-cells, better control of VL), whereas a Negative View of God predicted faster disease-progression over 4 years. Effect sizes were greater than those previously demonstrated for psychosocial variables known to predict HIV-disease-progression, such as depression and coping. Results remained significant even after adjusting for church attendance and psychosocial variables (health behaviors, mood, and coping). These results provide good initial evidence that spiritual beliefs may predict health outcomes.

  7. Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion Disease.

    Science.gov (United States)

    Fainstein, Nina; Dori, Dvir; Frid, Kati; Fritz, Alexa T; Shapiro, Ilona; Gabizon, Ruth; Ben-Hur, Tamir

    2016-01-01

    Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic proteins without an accompanying neurodegeneration pattern. The lack of a comprehensive model hinders efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice mimicking for genetic Creutzfeldt-Jacob disease as compared to age-matched wild-type mice. Mice exhibited a neurodegenerative process of progressive reduction in cortical neurons and synapses starting at age of 4-6 months, in accord with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with neurological disease progression, indicating these mice can serve as a model for neurodegenerative diseases.

  8. International vision requirements for driver licensing and disability pensions: using a milestone approach in characterization of progressive eye disease

    Directory of Open Access Journals (Sweden)

    Alain M Bron

    2010-11-01

    Full Text Available Alain M Bron1, Ananth C Viswanathan2, Ulrich Thelen3, Renato de Natale4, Antonio Ferreras5, Jens Gundgaard6, Gail Schwartz7, Patricia Buchholz81Department of Ophthalmology, University Hospital, Dijon, France; 2Glaucoma Research Unit, Moorfields Eye Hospital NHS Foundation Trust and Department of Genetics, University College of London Institute of Ophthalmology, London, UK; 3Private Practice, Munster, Germany; 4Ospedale Civile di Monselice, Monselice, Italy; 5Ophthalmology, Miguel Servet University Hospital, Zaragoza, Spain; 6COWI, Kolding, Denmark; 7Wilmer Eye Institute, Johns Hopkins University, Glaucoma Consultants, Baltimore, MD, USA; 8Patricia Buchholz Consulting, Karlsruhe, GermanyObjective: Low vision that causes forfeiture of driver’s licenses and collection of disability pension benefits can lead to negative psychosocial and economic consequences. The purpose of this study was to review the requirements for holding a driver’s license and rules for obtaining a disability pension due to low vision. Results highlight the possibility of using a milestone approach to describe progressive eye disease.Methods: Government and research reports, websites, and journal articles were evaluated to review rules and requirements in Germany, Spain, Italy, France, the UK, and the US.Results: Visual acuity limits are present in all driver’s license regulations. In most countries, the visual acuity limit is 0.5. Visual field limits are included in some driver’s license regulations. In Europe, binocular visual field requirements typically follow the European Union standard of ≥120°. In the US, the visual field requirements are typically between 110° and 140°. Some countries distinguish between being partially sighted and blind in the definition of legal blindness, and in others there is only one limit.Conclusions: Loss of driving privileges could be used as a milestone to monitor progressive eye disease. Forfeiture could be standardized as a

  9. Effect of fluoxetine on disease progression in a mouse model of ALS

    Science.gov (United States)

    Koschnitzky, J. E.; Quinlan, K. A.; Lukas, T. J.; Kajtaz, E.; Kocevar, E. J.; Mayers, W. F.; Siddique, T.

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are often prescribed to amyotrophic lateral sclerosis (ALS) patients; however, the impact of these prescriptions on ALS disease progression has not been systematically tested. To determine whether SSRIs impact disease progression, fluoxetine (Prozac, 5 or 10 mg/kg) was administered to mutant superoxide dismutase 1 (SOD1) mice during one of three age ranges: neonatal [postnatal day (P)5–11], adult presymptomatic (P30 to end stage), and adult symptomatic (P70 to end stage). Long-term adult fluoxetine treatment (started at either P30 or P70 and continuing until end stage) had no significant effect on disease progression. In contrast, neonatal fluoxetine treatment (P5-11) had two effects. First, all animals (mutant SOD1G93A and control: nontransgenic and SOD1WT) receiving the highest dose (10 mg/kg) had a sustained decrease in weight from P30 onward. Second, the high-dose SOD1G93A mice reached end stage ∼8 days (∼6% decrease in life span) sooner than vehicle and low-dose animals because of an increased rate of motor impairment. Fluoxetine increases synaptic serotonin (5-HT) levels, which is known to increase spinal motoneuron excitability. We confirmed that 5-HT increases spinal motoneuron excitability during this neonatal time period and therefore hypothesized that antagonizing 5-HT receptors during the same time period would improve disease outcome. However, cyproheptadine (1 or 5 mg/kg), a 5-HT receptor antagonist, had no effect on disease progression. These results show that a brief period of antidepressant treatment during a critical time window (the transition from neonatal to juvenile states) can be detrimental in ALS mouse models. PMID:24598527

  10. Progress for on-line acoustic emission monitoring of cracks in reactor systems

    International Nuclear Information System (INIS)

    Hutton, P.H.; Friesel, M.A.; Kurtz, R.J.

    1985-10-01

    This paper reviews FY1985 accomplishments and FY1986 plans for the NRC sponsored research program concerned with ''Acoustic Emission/Flaw Relationships for Inservice Monitoring of Nuclear Reactor Pressure Boundaries''. The objective of the acoustic emission (AE) monitoring program is to develop and validate the use of AE methods for continuous surveillance of reactor pressure boundaries to detect flaw growth. Topics discussed include testing AE monitoring on reactors, refinement of an AE signal identification relationship, study of slow crack growth rate effects on AE generation, and activity to produce an ASTM standard for AE monitoring and to gain ASME code acceptance of AE monitoring

  11. Disease Progression/Clinical Outcome Model for Castration-Resistant Prostate Cancer in Patients Treated with Eribulin

    NARCIS (Netherlands)

    Van Hasselt, J. G C; Gupta, A.; Hussein, Z.; Beijnen, J. H.; Schellens, J. H M; Huitema, A. D R

    2015-01-01

    Frameworks that associate cancer dynamic disease progression models with parametric survival models for clinical outcome have recently been proposed to support decision making in early clinical development. Here we developed such a disease progression clinical outcome model for castration-resistant

  12. Inflammation in Lafora Disease: Evolution with Disease Progression in Laforin and Malin Knock-out Mouse Models.

    Science.gov (United States)

    López-González, Irene; Viana, Rosa; Sanz, Pascual; Ferrer, Isidre

    2017-07-01

    Lafora progressive myoclonus epilepsy (Lafora disease, LD) is a fatal rare autosomal recessive neurodegenerative disorder characterized by the accumulation of insoluble ubiquitinated polyglucosan inclusions in the cytoplasm of neurons, which is most commonly associated with mutations in two genes: EPM2A, encoding the glucan phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. The present study analyzes possible inflammatory responses in the mouse lines Epm2a -/- (laforin knock-out) and Epm2b -/- (malin knock-out) with disease progression. Increased numbers of reactive astrocytes (expressing the GFAP marker) and microglia (expressing the Iba1 marker) together with increased expression of genes encoding cytokines and mediators of the inflammatory response occur in both mouse lines although with marked genotype differences. C3ar1 and CxCl10 messenger RNAs (mRNAs) are significantly increased in Epm2a -/- mice aged 12 months when compared with age-matched controls, whereas C3ar1, C4b, Ccl4, CxCl10, Il1b, Il6, Tnfα, and Il10ra mRNAs are significantly upregulated in Epm2b -/- at the same age. This is accompanied by increased protein levels of IL1-β, IL6, TNFα, and Cox2 particularly in Epm2b -/- mice. The severity of inflammatory changes correlates with more severe clinical symptoms previously described in Epm2b -/- mice. These findings show for the first time increased innate inflammatory responses in a neurodegenerative disease with polyglucosan intraneuronal deposits which increase with disease progression, in a way similar to what is seen in neurodegenerative diseases with abnormal protein aggregates. These findings also point to the possibility of using anti-inflammatory agents to mitigate the degenerative process in LD.

  13. Genome-wide analysis of disease progression in age-related macular degeneration.

    Science.gov (United States)

    Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

    2018-03-01

    Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

  14. Role of rasagiline in treating Parkinson’s disease: effect on disease progression

    OpenAIRE

    Fernandez, Hubert; Malaty,

    2009-01-01

    Irene A Malaty, Hubert H FernandezUniversity of Florida Movement Disorders Center, Gainesville, FL, USAAbstract: Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson’s disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson’s Disease Outpatients), and has shown ability to reduce off time in more advan...

  15. Role of rasagiline in treating Parkinson?s disease: Effect on disease progression

    OpenAIRE

    Malaty, Irene A; Fernandez, Hubert H

    2009-01-01

    Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson?s disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson?s Disease Outpatients), and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson?s Rasagiline: Efficacy and Safety in the Tr...

  16. Carotid artery disease progression and related neurologic events after carotid endarterectomy.

    Science.gov (United States)

    Avgerinos, Efthymios D; Go, Catherine; Ling, Jennifer; Naddaf, Abdallah; Steinmetz, Amy; Abou Ali, Adham N; Makaroun, Michel S; Chaer, Rabih A

    2016-08-01

    During the last decade, there has been a dramatic improvement in best medical treatment for patients with vascular disease. Yet, there is a paucity of contemporary long-term data for restenosis and contralateral internal carotid artery (ICA) progression. This study assessed ipsilateral and contralateral disease progression and cerebrovascular events after carotid endarterectomy (CEA). A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. End points were restenosis ≥50% and ≥70%, contralateral carotid disease progression (50%-69%, 70%-99%, or occlusion) and stroke. Survival analysis and Cox regression models were used to assess the effect of baseline predictors. During the 11-year study period, 1639 patients underwent 1782 CEAs (50.0% patch closure, 23.9% primary closure, 26.1% eversion, and 2.5% combined with coronary artery bypass grafting). The combined stroke/death rate was 2.6% overall and 1.8% in the asymptomatic cohort. The rate of restenosis ≥50% at 2, 5, and 10 years was 8.5%, 15.6%, 27.2%, and the rate for restenosis ≥70% was 3.4%, 6.5%, 10.2%, respectively. Restenosis ≥50% was predicted by hypertension (hazard ratio [HR], 2.09; P = .027), female gender (HR, 1.43; P = .042), and younger age (≤65 years; HR, 1.56; P = .016), but not by statins, surgical technique, symptoms, or other baseline risk factors. Restenoses remained asymptomatic in 125 of 148 (84.5%). Progression of contralateral ICA disease at 2, 5, and 10 years was estimated at 5.4%, 15.5%, and 46.8%, respectively. Contralateral progression was only predicted by smoking (HR, 1.74; P = .008). The stroke rate in patients with disease progression of the contralateral ICA was not different compared with those without progression (7.0% vs 3.3%; P = .063). Any-stroke rates at 2, 5, and 10 years were 4.6%, 7.3%, and 15.7%, respectively. Predictors were symptomatic lesion (HR, 1.48; P = .039), renal insufficiency, defined as a

  17. Pregnancy and HIV disease progression: a systematic review and meta-analysis.

    Science.gov (United States)

    Calvert, Clara; Ronsmans, Carine

    2015-02-01

    To assess whether pregnancy accelerates HIV disease progression. Studies comparing progression to HIV-related illness, low CD4 count, AIDS-defining illness, HIV-related death, or any death in HIV-infected pregnant and non-pregnant women were included. Relative risks (RR) for each outcome were combined using random effects meta-analysis and were stratified by antiretroviral therapy (ART) availability. 15 studies met the inclusion criteria. Pregnancy was not associated with progression to HIV-related illness [summary RR: 1.32, 95% confidence interval (CI): 0.66-2.61], AIDS-defining illness (summary RR: 0.97, 95% CI: 0.74-1.25) or mortality (summary RR: 0.97, 95% CI: 0.62-1.53), but there was an association with low CD4 counts (summary RR: 1.41, 95% CI: 0.99-2.02) and HIV-related death (summary RR: 1.65, 95% CI: 1.06-2.57). In settings where ART was available, there was no evidence that pregnancy accelerated progress to HIV/AIDS-defining illnesses, death and drop in CD4 count. In settings without ART availability, effect estimates were consistent with pregnancy increasing the risk of progression to HIV/AIDS-defining illnesses and HIV-related or all-cause mortality, but there were too few studies to draw meaningful conclusions. In the absence of ART, pregnancy is associated with small but appreciable increases in the risk of several negative HIV outcomes, but the evidence is too weak to draw firm conclusions. When ART is available, the effects of pregnancy on HIV disease progression are attenuated and there is little reason to discourage healthy HIV-infected women who desire to become pregnant from doing so. © 2014 John Wiley & Sons Ltd.

  18. RCRA [Resource Conservation and Recovery Act] ground-water monitoring projects for Hanford facilities: Annual progress report for 1988

    International Nuclear Information System (INIS)

    Fruland, R.M.; Lundgren, R.E.

    1989-04-01

    This report describes the progress during 1988 of 14 Hanford Site ground-water monitoring projects covering 16 hazardous waste facilities and 1 nonhazardous waste facility (the Solid Waste Landfill). Each of the projects is being conducted according to federal regulations based on the Resource Conservation and Recovery Act (RCRA) of 1976 and the State of Washington Administrative Code. 21 refs., 23 figs., 8 tabs

  19. CHI: A contemporaneous health index for degenerative disease monitoring using longitudinal measurements.

    Science.gov (United States)

    Huang, Yijun; Meng, Qiang; Evans, Heather; Lober, William; Cheng, Yu; Qian, Xiaoning; Liu, Ji; Huang, Shuai

    2017-09-01

    In this paper, we develop a novel formulation for contemporaneous patient risk monitoring by exploiting the emerging data-rich environment in many healthcare applications, where an abundance of longitudinal data that reflect the degeneration of the health condition can be continuously collected. Our objective, and the developed formulation, is fundamentally different from many existing risk score models for different healthcare applications, which mostly focus on predicting the likelihood of a certain outcome at a pre-specified time. Rather, our formulation translates multivariate longitudinal measurements into a contemporaneous health index (CHI) that captures patient condition changes over the course of progression. Another significant feature of our formulation is that, CHI can be estimated with or without label information, different from other risk score models strictly based on supervised learning. To develop this formulation, we focus on the degenerative disease conditions, for which we could utilize the monotonic progression characteristic (either towards disease or recovery) to learn CHI. Such a domain knowledge leads us to a novel learning formulation, and on top of that, we further generalize this formulation with a capacity to incorporate label information if available. We further develop algorithms to mitigate the challenges associated with the nonsmooth convex optimization problem by first identifying its dual reformulation as a constrained smooth optimization problem, and then, using the block coordinate descent algorithm to iteratively solve the optimization with a derived efficient projection at each iteration. Extensive numerical studies are performed on both synthetic datasets and real-world applications on Alzheimer's disease and Surgical Site Infection, which demonstrate the utility and efficacy of the proposed method on degenerative conditions that include a wide range of applications. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. PLOS Neglected Tropical Diseases: Ten years of progress in neglected tropical disease control and elimination … More or less.

    Directory of Open Access Journals (Sweden)

    Peter Hotez

    2017-04-01

    Full Text Available This year PLOS Neglected Tropical Diseases (PLOS NTDs celebrates its tenth anniversary following the publication of the first issue in 2007 [1]. When PLOS NTDs was founded, the framework of the neglected tropical diseases (NTDs as an alternative to "other diseases" (as they were then referred to in the Millennium Development Goals was just getting started-especially for Africa [2, 3]. In the decade since, PLOS NTDs has overseen enormous successes in NTD control and elimination. Here, we want to briefly review the ten year progress made towards the control or elimination of the diseases now identified by the WHO as NTDs. Many of the details are highlighted in PLOS NTDs papers cited here, but the summary information is based on the recently released Global Burden of Disease (GBD Study 2015 (also launched with Gates Foundation support that summarized past-decade changes in disease prevalence, mortality, or disability rates (from the years 2005 to 2015 [4-6], as well as the GBD Study 2013 that summarizes disease prevalence changes over a longer time horizon from 1990 to 2013 [7].

  1. Autologous neural progenitor cell transplantation into newborn mice modeling for E200K genetic prion disease delays disease progression.

    Science.gov (United States)

    Frid, Kati; Binyamin, Orli; Fainstein, Nina; Keller, Guy; Ben-Hur, Tamir; Gabizon, Ruth

    2018-05-01

    TgMHu2ME199K mice, a transgenic line mimicking genetic prion disease, are born healthy and gradually deteriorate to a terminal neurological condition concomitant with the accumulation of disease-related PrP. To investigate whether transplantation of neural progenitor cells (NPCs) to these mice can delay disease aggravation, we first tested the properties of mutant PrP in homogenates and enriched NPCs from TgMHu2ME199K embryos, as compared to PrP in sick TgMHu2ME199K brains. Next, we tested the clinical effect of NPCs transplantation into newborn TgMHu2ME199K mice. We show that mutant PrP does not convert into a disease-related isoform while in progenitor cells. Most important, transplantation of both wild type and transgenic NPCs significantly delayed the progression of spontaneous prion disease in TgMHu2ME199K mice. While the strong clinical effect was not accompanied by a reduced accumulation of disease-related PrP, treated mouse brains presented a significant reduction in amyloid glycosaminoglycans and preservation of neurogenesis levels, indicating a strong neuroprotective effect. These results may encourage the investigation of new pathways for treatment in these terrible diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

    Science.gov (United States)

    Rosiñol, Laura; García-Sanz, Ramón; Lahuerta, Juan José; Hernández-García, Miguel; Granell, Miquel; de la Rubia, Javier; Oriol, Albert; Hernández-Ruiz, Belén; Rayón, Consuelo; Navarro, Isabel; García-Ruiz, Juan Carlos; Besalduch, Joan; Gardella, Santiago; Jiménez, Javier López; Díaz-Mediavilla, Joaquín; Alegre, Adrián; Miguel, Jesús San; Bladé, Joan

    2012-01-01

    Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:NCT00560053) PMID:22058223

  3. The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease

    DEFF Research Database (Denmark)

    Jafar, Tazeen H; Stark, Paul C; Schmid, Christopher H

    2005-01-01

    BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors...... of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine......%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P

  4. Gut Microbiota in HIV Infection: Implication for Disease Progression and Management

    Directory of Open Access Journals (Sweden)

    Felix Chinweije Nwosu

    2014-01-01

    Full Text Available Survival rates among HIV patients have significantly improved since the introduction of antiretroviral therapy (ART in HIV management. However, persistent disease progression and clinical complications in virally suppressed individuals point to additional contributing factors other than HIV replication; microbial translocation is one such factor. The role of underlying commensal microbes and microbial products that traverse the intestinal lumen into systemic circulation in the absence of overt bacteraemia is under current investigation. This review focuses on current knowledge of the complex microbial communities and microbial markers involved in the disruption of mucosal immune T-cells in the promotion of inflammatory processes in HIV infections. Unanswered questions and aims for future studies are addressed. We provide perspective for discussing potential future therapeutic strategies focused on modulating the gut microbiota to abate HIV disease progression.

  5. ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

    Science.gov (United States)

    Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

    2017-03-09

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

  6. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

    Science.gov (United States)

    Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

    2017-01-01

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

  7. CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP.

    Science.gov (United States)

    Rojas, Julio C; Bang, Jee; Lobach, Iryna V; Tsai, Richard M; Rabinovici, Gil D; Miller, Bruce L; Boxer, Adam L

    2018-01-23

    To determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP). We compared the ability of baseline CSF β-amyloid 1-42 , tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients. Higher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS ( p = 0.004, false discovery rate-corrected) and SEADL ( p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS ( p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL ( p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau ( p = 0.003) or NfL ( p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ≤ 0.029 and 0.008, respectively). Both CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease. Copyright © 2017 American Academy of Neurology.

  8. NMR-based lipidomic analysis of blood lipoproteins differentiates the progression of coronary heart disease.

    Science.gov (United States)

    Kostara, Christina E; Papathanasiou, Athanasios; Psychogios, Nikolaos; Cung, Manh Thong; Elisaf, Moses S; Goudevenos, John; Bairaktari, Eleni T

    2014-05-02

    Abnormal lipid composition and metabolism of plasma lipoproteins play a crucial role in the pathogenesis of coronary heart disease (CHD). A (1)H NMR-based lipidomic approach was used to investigate the correlation of coronary artery stenosis with the atherogenic (non-HDL) and atheroprotective (HDL) lipid profiles in 99 patients with CHD of various stages of disease and compared with 60 patients with normal coronary arteries (NCA), all documented in coronary angiography. The pattern recognition models created from lipid profiles predicted the presence of CHD with a sensitivity of 87% and a specificity of 88% in the HDL model and with 90% and 89% in the non-HDL model, respectively. Patients with mild, moderate, and severe coronary artery stenosis were progressively differentiated from those with NCA in the non-HDL model with a statistically significant separation of severe stage from both mild and moderate. In the HDL model, the progressive differentiation of the disease stages was statistically significant only between patients with mild and severe coronary artery stenosis. The lipid constituents of lipoproteins that mainly characterized the initial stages and then the progression of the disease were the high levels of saturated fatty acids in lipids in both HDL and non-HDL particles, the low levels of HDL-phosphatidylcholine, HDL-sphingomyelin, and omega-3 fatty acids and linoleic acid in lipids in non-HDL particles. The conventional lipid marker, total cholesterol, found in low levels in HDL and in high levels in non-HDL, also contributed to the onset of the disease but with a much lower coefficient of significance. (1)H NMR-based lipidomic analysis of atherogenic and atheroprotective lipoproteins could contribute to the early evaluation of the onset of coronary artery disease and possibly to the establishment of an appropriate therapeutic option.

  9. A simulation of 'schedule-cost' progress monitoring system in nuclear power project management

    International Nuclear Information System (INIS)

    Song Haitao; Huang Zhongping; Zhang Zemin; Wang Zikai

    2010-01-01

    The objective of project management is to find the optimal balance between progress and cost according to the project requirements. Traditional method always manages progress and cost separately. However, domestic and international experience indicated that the interactions between these two factors are crucial in the project implementation. Modern project managers have to manage and maintain a 'Progress - Cost' joint control framework. Such a model is applied into a sub-project of a nuclear power project using Simulink in this paper. It helps to identify and correct the deviations of the project. Earned Value Management is used by the project manager to quantify the cost of the project and progress of implementation. The budget plan value, actual value, earned value are three important parameters to measure cost and progress of the project. The experimental results illustrated that the method gives a more comprehensive performance evaluation of the project. (authors)

  10. Phase separation of the plasma membrane in human red blood cells as a potential tool for diagnosis and progression monitoring of type 1 diabetes mellitus.

    Science.gov (United States)

    Maulucci, Giuseppe; Cordelli, Ermanno; Rizzi, Alessandro; De Leva, Francesca; Papi, Massimiliano; Ciasca, Gabriele; Samengo, Daniela; Pani, Giovambattista; Pitocco, Dario; Soda, Paolo; Ghirlanda, Giovanni; Iannello, Giulio; De Spirito, Marco

    2017-01-01

    Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins can alter lipid density, packing and interactions, and are considered an important factor that affects fluidity variation in membranes. Red blood cells (RBC) membrane physical state, showing pronounced alterations in Type 1 diabetes mellitus (T1DM), could be the ideal candidate for monitoring the disease progression and the effects of therapies. On these grounds, the measurement of RBC membrane fluidity alterations can furnish a more sensitive index in T1DM diagnosis and disease progression than Glycosylated hemoglobin (HbA1c), which reflects only the information related to glycosylation processes. Here, through a functional two-photon microscopy approach we retrieved fluidity maps at submicrometric scale in RBC of T1DM patients with and without complications, detecting an altered membrane equilibrium. We found that a phase separation between fluid and rigid domains occurs, triggered by systemic effects on membranes fluidity of glycation and oxidation. The phase separation patterns are different among healthy, T1DM and T1DM with complications patients. Blood cholesterol and LDL content are positively correlated with the extent of the phase separation patterns. To quantify this extent a machine learning approach is employed to develop a Decision-Support-System (DSS) able to recognize different fluidity patterns in RBC. Preliminary analysis shows significant differences(pBlood cells is a potential tool for diagnosis and progression monitoring of type 1 diabetes mellitus, and could allow customization and the selection of medical treatments in T1DM in clinical settings, and enable the early detection of complications.

  11. Phase separation of the plasma membrane in human red blood cells as a potential tool for diagnosis and progression monitoring of type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Giuseppe Maulucci

    Full Text Available Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins can alter lipid density, packing and interactions, and are considered an important factor that affects fluidity variation in membranes. Red blood cells (RBC membrane physical state, showing pronounced alterations in Type 1 diabetes mellitus (T1DM, could be the ideal candidate for monitoring the disease progression and the effects of therapies. On these grounds, the measurement of RBC membrane fluidity alterations can furnish a more sensitive index in T1DM diagnosis and disease progression than Glycosylated hemoglobin (HbA1c, which reflects only the information related to glycosylation processes. Here, through a functional two-photon microscopy approach we retrieved fluidity maps at submicrometric scale in RBC of T1DM patients with and without complications, detecting an altered membrane equilibrium. We found that a phase separation between fluid and rigid domains occurs, triggered by systemic effects on membranes fluidity of glycation and oxidation. The phase separation patterns are different among healthy, T1DM and T1DM with complications patients. Blood cholesterol and LDL content are positively correlated with the extent of the phase separation patterns. To quantify this extent a machine learning approach is employed to develop a Decision-Support-System (DSS able to recognize different fluidity patterns in RBC. Preliminary analysis shows significant differences(p<0.001 among healthy, T1DM and T1DM with complications patients. The development of an assay based on Phase separation of the plasma membrane of the Red Blood cells is a potential tool for diagnosis and progression monitoring of type 1 diabetes mellitus, and could allow customization and the selection of medical treatments in T1DM in clinical settings, and enable the early detection of complications.

  12. Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers.

    Directory of Open Access Journals (Sweden)

    Bulbulgul Aumakhan

    Full Text Available BACKGROUND: The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear. METHODS: Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit. RESULTS: A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p = 0.004, an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001 and 51 to 101 reduced CD4+ T cells/mm(3 over time compared to asymptomatic HSV-2 infection (trend p<0.001. CONCLUSIONS: HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression.

  13. Klinefelter′s syndrome associated with progressive muscular atrophy simulating Kennedy′s disease

    OpenAIRE

    Pedro Enrique Jiménez Caballero

    2012-01-01

    Kennedy's disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter's syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klin...

  14. Computed tomographic findings of progressive supranuclear palsy compared with Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Yuki, Nobuhiro; Sato, Shuzo; Yuasa, Tatsuhiko; Ito, Jusuke; Miyatake, Tadashi [Niigata Univ. (Japan). School of Dentistry

    1990-10-01

    We investigated computed tomographic (CT) films of 4 pathologically documented cases of progressive supranuclear palsy (PSP) in which the clinical presentations were atypical and compared the findings with those of 15 patients with Parkinson's disease (PD). Dilatation of the third ventricle, atrophy of the midbrain tegmentum, and enlargement of the interpeduncular cistern toward the aqueduct were found to be the characteristic findings in PSP. Thus, radiological findings can be useful when the differential diagnosis between PSP and PD is clinically difficult. (author).

  15. Superoxide radical dismutation as protective mechanism to hamper the progression of Parkinson's disease

    OpenAIRE

    Filograna, Roberta

    2015-01-01

    Abstract Parkinson's disease (PD) is a degenerative neurological syndrome characterized by the preferential loss of dopaminergic (DAergic) neurons in the Substantia Nigra pars compacta. PD is still incurable and conventional therapies treat only symptoms to improve the quality of life. Therefore, there is a impelling need to find out new therapeutic strategies that not only provide symptomatic relief but also halt or reverse the neuronal damage hampering PD progression. Even though the pat...

  16. Factors That Affect Disease Progression After First Attack of Acute Pancreatitis.

    Science.gov (United States)

    Bertilsson, Sara; Swärd, Per; Kalaitzakis, Evangelos

    2015-09-01

    Little is known about recurrence of pancreatitis after an initial episode, and little is known about how the disease progresses or what factors affect progression. We performed a population-based study of patients with acute pancreatitis (AP) to determine their outcomes and associated factors. We performed a retrospective study of patients with first-time AP from 2003 through 2012 in a well-defined area of Sweden. Data were collected from medical records on disease etiology, severity (according to the Atlanta classification), recurrence of AP, subsequent chronic pancreatitis, and mortality. Patients were followed up for a median time of 4.6 years, until death or the end of 2013. We identified 1457 patients with first-time AP (48% biliary disease, 17% alcohol-associated, 9.9% severe); 23% of patients had 1 or more recurrences. Risk for recurrence was significantly higher among smokers (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.03-1.95; P = .03), patients with alcohol-associated AP (HR, 1.58; 95% CI, 1.25-2.23; P chronic pancreatitis, although alcohol-associated AP progressed most frequently (2.8/100 patient-years). Patients with recurrent AP were at the highest risk for chronic pancreatitis (HR, 6.74; 95% CI, 4.02-11.3; P associated AP (HR, 3.10; 95% CI, 2.05-5.87; P associated only with organ failure (odds ratio, 71.17; 95% CI, 21.14-239.60; P chronic pancreatitis. Recurrence increases the risk for progression to chronic pancreatitis. Most patients who die upon disease recurrence have biliary AP. Copyright © 2015. Published by Elsevier Inc.

  17. Progressive white-matter disease with primary cerebellar involvement: a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Yalcinkaya, C. [Division of Child Neurology, Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul (Turkey); Arslanoglu, I. [Division of Endocrinology, Department of Paediatrics, Goeztepe Hospital, Istanbul (Turkey); Islak, C. [Division of Neuroradiology, Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul (Turkey); Aydin, A. [Division of Metabolic Disease, Department of Paediatrics, Cerrahpasa Medical Faculty, Istanbul University, Istanbul (Turkey); Boltshauser, E. [Division of Paediatric Neurology, University Children' s Hospital, Steinwiesstrasse 75, 8032 Zuerich (Switzerland)

    2002-09-01

    Although its metabolic basis has not yet been clarified, we report a progressive white-matter disease in a Turkish girl, starting in the cerebellum and spreading to supratentorial white matter. The onset was at the age of 2.5 years with diabetes insipidus, followed by ataxia and pyramidal signs resulting in loss of walking. Aqueduct stenosis was first recognised at the age of 8 years. To our knowledge, this MRI and clinical pattern does not correspond to a recognised, well-defined white-matter disease and may indicate a separate entity. (orig.)

  18. Progressive white-matter disease with primary cerebellar involvement: a separate entity?

    International Nuclear Information System (INIS)

    Yalcinkaya, C.; Arslanoglu, I.; Islak, C.; Aydin, A.; Boltshauser, E.

    2002-01-01

    Although its metabolic basis has not yet been clarified, we report a progressive white-matter disease in a Turkish girl, starting in the cerebellum and spreading to supratentorial white matter. The onset was at the age of 2.5 years with diabetes insipidus, followed by ataxia and pyramidal signs resulting in loss of walking. Aqueduct stenosis was first recognised at the age of 8 years. To our knowledge, this MRI and clinical pattern does not correspond to a recognised, well-defined white-matter disease and may indicate a separate entity. (orig.)

  19. Research progress of rehabilitation therapy in Parkinson's disease and its mechanism

    Directory of Open Access Journals (Sweden)

    Jin LIU

    2017-07-01

    Full Text Available Parkinson's disease (PD is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rehabilitation therapy can delay the development of disease, improve motor symptoms and non - motor symptoms (NMS, and consequently improve the activities of daily living (ADL in patients with PD. The mechanism of rehabilitation improving the symptoms of PD is very complex, involving a variety of molecular mechanisms. Thus, this review will focus on the effect of rehabilitation therapy on PD and the underlying molecular mechanism including neurotransmitters, trophic factors, synaptic plasticity and immune system. DOI: 10.3969/j.issn.1672-6731.2017.06.003

  20. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    Science.gov (United States)

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  1. Markers, Cofactors and Staging Systems in the Study of HIV Disease Progression: A Review

    Directory of Open Access Journals (Sweden)

    MC Portela

    1997-07-01

    Full Text Available This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined

  2. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    Science.gov (United States)

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  3. Progress toward an integrated understanding of Parkinson's disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Maxime W.C. Rousseaux

    2017-07-01

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder after Alzheimer's disease, affecting over 10 million individuals worldwide. While numerous effective symptomatic treatments are currently available, no curative or disease-modifying therapies exist. An integrated, comprehensive understanding of PD pathogenic mechanisms will likely address this unmet clinical need. Here, we highlight recent progress in PD research with an emphasis on promising translational findings, including (i advances in our understanding of disease susceptibility, (ii improved knowledge of cellular dysfunction, and (iii insights into mechanisms of spread and propagation of PD pathology. We emphasize connections between these previously disparate strands of PD research and the development of an emerging systems-level understanding that will enable the next generation of PD therapeutics.

  4. Progressive atlanto-axial subluxation in Behcet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang-hyuk [Chonbuk National University Hospital, Department of Neurosurgery, Jeonju City, Jeonbuk (Korea); Eoh, Whan [Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Neurosurgery, Seoul (Korea)

    2010-03-15

    Behcet's disease is a chronic inflammatory condition involving several organs, such as the skin, mucous membranes, eyes, joints, intestines, lungs and central nervous system. It rarely affects the spinal column. We describe a case of progressive atlanto-axial subluxation in a 44-year-old woman with Behcet's disease. The patient started complaining of posterior neck pain 10 years after the diagnosis of her Behcet's disease. Initial radiographs showed no abnormal finding, but follow-up radiographs 6 month later demonstrated atlanto-axial subluxation. To the best of our knowledge, this is the second reported case in the worldwide literature of an atlanto-axial instability in a patient with Behcet's disease. (orig.)

  5. Identification and Progression of Heart Disease Risk Factors in Diabetic Patients from Longitudinal Electronic Health Records

    Directory of Open Access Journals (Sweden)

    Jitendra Jonnagaddala

    2015-01-01

    Full Text Available Heart disease is the leading cause of death worldwide. Therefore, assessing the risk of its occurrence is a crucial step in predicting serious cardiac events. Identifying heart disease risk factors and tracking their progression is a preliminary step in heart disease risk assessment. A large number of studies have reported the use of risk factor data collected prospectively. Electronic health record systems are a great resource of the required risk factor data. Unfortunately, most of the valuable information on risk factor data is buried in the form of unstructured clinical notes in electronic health records. In this study, we present an information extraction system to extract related information on heart disease risk factors from unstructured clinical notes using a hybrid approach. The hybrid approach employs both machine learning and rule-based clinical text mining techniques. The developed system achieved an overall microaveraged F-score of 0.8302.

  6. Predictors of high healthcare resource utilization and liver disease progression among patients with chronic hepatitis C.

    Science.gov (United States)

    LaMori, Joyce; Tandon, Neeta; Laliberté, François; Germain, Guillaume; Pilon, Dominic; Lefebvre, Patrick; Prabhakar, Avinash

    2016-01-01

    Since hepatitis C virus therapy is typically prioritized for patients with more advanced disease, predicting which patients will progress could help direct scarce resources to those likely to benefit most. This study aims to identify demographics and clinical characteristics associated with high healthcare resource utilization (HRU) and liver disease progression among CHC patients. Using health insurance claims (January 2001-March 2013), adult patients with ≥2 CHC claims (ICD-9-CM: 070.44 or 070.54), and ≥6 months of continuous insurance coverage before and ≥36 months after the first CHC diagnosis were included. Patients with human immunodeficiency virus were excluded. Generalized estimating equations were used to identify the demographic and clinical characteristics of being in the 20% of patients with the highest HRU. Factors predicting liver disease progression were also identified. In the study population (n = 4898), liver disease severity and both CHC- and non-CHC-related comorbidities and conditions were strong predictors of high healthcare costs, with odds ratios (ORs; 95% confidence interval [CI]) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities/conditions of 2.78 (2.48-3.12) and 2.19 (1.76-2.72), respectively. CHC- and non-CHC-related comorbidities and conditions were also strong predictors of liver disease progression with ORs (95% CI) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities and conditions of 2.18 (1.83-2.60) and 1.50 (1.14-1.97), respectively. Potential inaccuracies in claims data, information or classification bias, and findings based on a privately insured population. This study suggests that CHC patients with high healthcare resource utilization have a high level of comorbidity at baseline and also that non-CHC comorbidities and conditions are strong predictors of high HRU. Non-cirrhotic CHC patients with one or more comorbidities are at high risk of progressing to cirrhosis or end-stage liver disease.

  7. Radiographic assessment of disease progression in rheumatoid arthritis patients undergoing early disease-modifying anti-rheumatic drug treatment

    International Nuclear Information System (INIS)

    Wick, M.C.

    2002-04-01

    Rheumatoid arthritis (RA) is a common systemic disease predominantly involving the joints. Since the pathogenesis, etiology and pathophysiological mechanisms of RA have only been partially elucidated, a definitive therapy has not been established. Precise diagnosis and follow-up therapy requires objective quantification, and radiological analyses are considered to be the most appropriate method. The aim of this study was to retrospectively determine the time-dependent progression of joint damage in patients with pharmacologically-treated RA, and to determine which therapeutic agents demonstrate the highest efficacy. Outpatient records, laboratory values, therapy schemes and radiographs from hands and feet of 150 RA patients were collected, analyzed and statistically evaluated. Radiographs were quantified using the Larsen score and supportively using the 'RheumaCoach-Rheumatology' computer software. Our observations reveal that radiologically-detectable damage is most pronounced during the first year of disease, while mitigated and generally progressing linearly thereafter. Overall Larsen scores linearly increased from year 0 to 10 (r=0.853), during which the mean Larsen score increased 7.93 ± 0.76 per year. During the first year, RA progression was similar regardless of the medication administered (gold-compounds, AU; chloroquine, CQ; methotrexate, MTX; sulfasalazine SSZ). While MTX and CQ treatment showed no difference when examined as mean 5-year increment of Larsen score, AU and SSZ showed up to 3 fold higher RA progression compared with MTX. The Larsen score in year 1 did not correlate with that of years 2 to 5. In contrast, Larsen scores in year 2 were linearly related to each of the subsequent 3 years. Despite similar ESR values in various medication groups, cumulative ESR correlated with RA progression, and its reduction with therapeutic efficacy. In conclusion, this study found that, (i) early DMARD-treated RA progressed more rapidly during the first than

  8. Progress of optical sensor system for health monitoring of bridges at Chongqing University

    Science.gov (United States)

    Chen, W.; Fu, Y.; Zhu, Y.; Huang, S.

    2005-02-01

    With decades of research experience on optical sensors, Optoelectronic Technology Lab of Chongqing University (OTLCU) has studied on a variety of sensors system designed for practical use in health monitoring. In OTLCU, embedded and surface mounted fiber Fabry-Perot strain sensor has been developed for monitoring the local strain of both concrete and steel truss bridge. Optoelectronic deflect meter, with a group of optical level sensor in a series connected pipe, was developed for deflection monitoring and line shape monitoring of the bridges. Laser deflect meter, with a laser pointer and a sensors array, has been also developed for a dynamic deflection monitoring of the bridges. To monitoring the 2-Dimentional displacement of the bridge, a self-calibrating imaging system was developed. All these sensor systems have been applied in different bridges successfully. This paper briefly describes principle of these optical sensing systems, and also gives some representative results of the system in practical application of bridges.

  9. Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression

    Directory of Open Access Journals (Sweden)

    Hua Chen

    2016-12-01

    Full Text Available Early detection is critical in prevention and treatment of kidney disease. However currently clinical laboratory and histopathological tests do not provide region-specific and accurate biomarkers for early detection of kidney disease. The present study was conducted to identify sensitive biomarkers for early detection and progression of tubulo-interstitial nephropathy in aristolochic acid I-induced rats at weeks 4, 8 and 12. Biomarkers were validated using aristolochic acid nephropathy (AAN rats at week 24, adenine-induced chronic kidney disease (CKD rats and CKD patients. Compared with control rats, AAN rats showed anemia, increased serum urea and creatinine, progressive renal interstitial fibrosis, activation of nuclear factor-kappa B, and up-regulation of pro-inflammatory, pro-oxidant, and pro-fibrotic proteins at weeks 8 and 12. However, no significant difference was found at week 4. Metabolomics identified 12-ketodeoxycholic acid, taurochenodesoxycholic acid, LPC(15:0 and docosahexaenoic acid as biomarkers for early detection of tubulo-interstitial nephropathy. With prolonging aristolochic acid I exposure, LPE(20:2, cholic acid, chenodeoxycholic acid and LPC(17:0 were identified as biomarkers for progression from early to advanced AAN and lysoPE(22:5, indoxyl sulfate, uric acid and creatinine as biomarkers of advanced AAN. These biomarkers were reversed by treatment of irbesartan and ergone in AAN rats at week 24 and adenine-induced CKD rats. In addition, these biomarkers were also reversed by irbesartan treatment in CKD patients.

  10. Impairment of Vowel Articulation as a Possible Marker of Disease Progression in Parkinson's Disease

    OpenAIRE

    Skodda, Sabine; Grönheit, Wenke; Schlegel, Uwe

    2012-01-01

    PURPOSE: The aim of the current study was to survey if vowel articulation in speakers with Parkinson's disease (PD) shows specific changes in the course of the disease. METHOD: 67 patients with PD (42 male) and 40 healthy speakers (20 male) were tested and retested after an average time interval of 34 months. Participants had to read a given text as source for subsequent calculation of the triangular vowel space area (tVSA) and vowel articulation index (VAI). Measurement of tVSA and VAI were ...

  11. Continuous A.E. monitoring of nuclear systems: some feasibility studies now in-progress in France

    International Nuclear Information System (INIS)

    Roget, J.; Germain, J.L.

    1986-01-01

    Continuous A.E. monitoring of Nuclear systems can give some unique information about abnormal behaviour (leak appearance...) or crack initiation or propagation. Some feasibility studies have been undertaken in France in this field and this paper presents the results we have got in two cases. The study showed that an A.E. surveillance of pressurized safety valves indicates the appearance or the presence of a leak. Functioning noise is not a problem in this case. Secondly a large study have been undertaken to test the resistance of the pipe inner sleeve to thermal fatigue. An A.E. monitoring showed that it is possible to separate A.E. due to Crack extension from other signals by a location method in spite of high noise level. A.E. seems applicable for continuous monitoring. So, complementary tests are in progress to confirm and improve these results

  12. Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation

    NARCIS (Netherlands)

    Hilker, R; Portman, AT; Voges, J; Staal, MJ; Burghaus, L; van Laar, T; Koulousakis, A; Maguire, RP; Pruim, J; de Jong, BM; Herholz, K; Sturm, [No Value; Heiss, WD; Leenders, KL

    Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications,

  13. Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis.

    Science.gov (United States)

    Cobo, Gabriela; Hecking, Manfred; Port, Friedrich K; Exner, Isabella; Lindholm, Bengt; Stenvinkel, Peter; Carrero, Juan Jesús

    2016-07-01

    Sex and gender differences are of fundamental importance in most diseases, including chronic kidney disease (CKD). Men and women with CKD differ with regard to the underlying pathophysiology of the disease and its complications, present different symptoms and signs, respond differently to therapy and tolerate/cope with the disease differently. Yet an approach using gender in the prevention and treatment of CKD, implementation of clinical practice guidelines and in research has been largely neglected. The present review highlights some sex- and gender-specific evidence in the field of CKD, starting with a critical appraisal of the lack of inclusion of women in randomized clinical trials in nephrology, and thereafter revisits sex/gender differences in kidney pathophysiology, kidney disease progression, outcomes and management of haemodialysis care. In each case we critically consider whether apparent discrepancies are likely to be explained by biological or psycho-socioeconomic factors. In some cases (a few), these findings have resulted in the discovery of disease pathways and/or therapeutic opportunities for improvement. In most cases, they have been reported as merely anecdotal findings. The aim of the present review is to expose some of the stimulating hypotheses arising from these observations as a preamble for stricter approaches using gender for the prevention and treatment of CKD and its complications. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  14. A longitudinal study of Stargardt disease: quantitative assessment of fundus autofluorescence, progression, and genotype correlations.

    Science.gov (United States)

    Fujinami, Kaoru; Lois, Noemi; Mukherjee, Rajarshi; McBain, Vikki A; Tsunoda, Kazushige; Tsubota, Kazuo; Stone, Edwin M; Fitzke, Fred W; Bunce, Catey; Moore, Anthony T; Webster, Andrew R; Michaelides, Michel

    2013-12-17

    We characterized subtypes of fundus autofluorescence (AF) and the progression of retinal atrophy, and correlated these findings with genotype in Stargardt disease. Full clinical examination and AF imaging was undertaken in 68 patients with Stargardt disease. The baseline data were compared to those at follow-up. Patients were classified into three AF subtypes: type 1 had a localized low signal at the fovea surrounded by a homogeneous background, type 2 had a localized low signal at the macula surrounded by a heterogeneous background with numerous foci of abnormal signal, and type 3 had multiple low signal areas at the posterior pole with a heterogeneous background. At baseline, there were 19 patients with type 1, 41 with type 2, and 8 with type 3 disease. The areas of reduced AF signal were measured and rate of atrophy enlargement (RAE) was calculated as the difference of the atrophy size over time (mm²) divided by the follow-up interval (years). Molecular screening of ABCA4 was undertaken. The mean follow-up interval was 9.1 years. A total of 42% cases with type 1 disease progressed to type 2, and 12% with type 2 progressed to type 3. The RAE (mm²/y) based upon baseline AF subtypes was significantly different; 0.06 in type 1, 0.67 in type 2, and 4.37 in type 3. ABCA4 variants were identified in 57 patients. There was a significant association between AF subtype and genotype. The AF pattern at baseline influences the enlargement of atrophy over time and has genetic correlates. These data are likely to assist in the provision of counseling on prognosis in Stargardt disease and be valuable for future clinical trials.

  15. Droplet Digital PCR for BCR/ABL(P210) Detecting of CML: A High Sensitive Method of the Minimal Residual Disease& Disease Progression.

    Science.gov (United States)

    Wang, Wen-Jun; Zheng, Chao-Feng; Liu, Zhuang; Tan, Yan-Hong; Chen, Xiu-Hua; Zhao, Bin-Liang; Li, Guo-Xia; Xu, Zhi-Fang; Ren, Fang-Gang; Zhang, Yao-Fang; Chang, Jian-Mei; Wang, Hong-Wei

    2018-04-25

    The present study intended to establish a droplet digital PCR (dd-PCR) for monitoring minimal residual disease (MRD) in patients with BCR/ABL (P210)-positive CML, thereby achieving deep-level monitoring of tumor load and determining the efficacy for guided clinically individualized treatment. Using dd-PCR and RT-qPCR, two cell suspensions were obtained from K562 cells and normal peripheral blood mononuclear cells by gradient dilution and were measured at the cellular level. At peripheral blood(PB) level, 61 cases with CML-chronic phase (CML-CP) were obtained after tyrosine kinase inhibitors (TKIs) treatment and regular follow-ups. By RT-qPCR, BCR/ABL (P210) fusion gene was undetectable in PB after three successive analyses, which were performed once every three months. At the same time, dd-PCR was performed simultaneously with the last equal amount of cDNA. Ten CML patients with MR4.5 were followed up by the two methods. At the cellular level, consistency of results of dd-PCR and RT-qPCR reached R 2 ≥0.99, with conversion equation of Y=33.148X 1.222 (Y: dd-PCR results; X: RT-qPCR results). In the dd-PCR test, 11 of the 61 CML patients (18.03%) tested positive and showed statistically significant difference (PPCR 3 months earlier than by RT-qPCR. In contrast with RT-qPCR, dd-PCR is more sensitive, thus enabling accurate conversion of dd-PCR results into internationally standard RT-qPCR results by conversion equation, to achieve a deeper molecular biology-based stratification of BCR/ABL(P210) MRD. It has some reference value to monitor disease progression in clinic. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Idaho Natural Production Monitoring and Evaluation : Annual Progress Report February 1, 2007 - January 31, 2008.

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Timothy; Johnson, June; Putnam, Scott

    2008-12-01

    River stocks of steelhead and spring/summer Chinook salmon still have significant natural reproduction and thus are the focal species for this project's investigations. The overall goal is to monitor the abundance, productivity, distribution, and stock-specific life history characteristics of naturally produced steelhead trout and Chinook salmon in Idaho (IDFG 2007). We have grouped project tasks into three objectives, as defined in our latest project proposal and most recent statement of work. The purpose of each objective involves enumerating or describing individuals within the various life stages of Snake River anadromous salmonids. By understanding the transitions between life stages and associated controlling factors, we hope to achieve a mechanistic understanding of stock-specific population dynamics. This understanding will improve mitigation and recovery efforts. Objective 1. Measure 2007 adult escapement and describe the age structure of the spawning run of naturally produced spring/summer Chinook salmon passing Lower Granite Dam. Objective 2. Monitor the juvenile production of Chinook salmon and steelhead trout for the major population groups (MPGs) within the Clearwater and Salmon subbasins. Objective 3. Evaluate life cycle survival and the freshwater productivity/production of Snake River spring/summer Chinook salmon. There are two components: update/refine a stock-recruit model and estimate aggregate smolt-to-adult survival. In this annual progress report, we present technical results for work done during 2007. Part 2 contains detailed results of INPMEP aging research and estimation of smolt-to-adult return rates for wild and naturally produced Chinook salmon (Objectives 1 and 3). Part 3 is a report on the ongoing development of a stock-recruit model for the freshwater phase of spring/summer Chinook salmon in the Snake River basin (Objective 3). Part 4 is a summary of the parr density data (Objective 2) collected in 2007 using the new site selection

  17. The fundamental role of mechanical properties in the progression of cancer disease and inflammation

    Science.gov (United States)

    Mierke, Claudia Tanja

    2014-07-01

    The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in

  18. NRC TLD Direct Radiation Monitoring Network. Progress report, October-December 1985. Volume 5, No. 4

    International Nuclear Information System (INIS)

    Jang, J.; Rabatin, K.; Cohen, L.

    1986-05-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1985. It provides the ambient radiation levels measured in the vicinity of 74 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program

  19. NRC TLD [thermoluminescent dosimeter] Direct Radiation Monitoring Network: Progress report, October--December 1988

    International Nuclear Information System (INIS)

    Struckmeyer, R.; NcNamara, N.

    1989-04-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1988. It provides the ambient radiation levels measured in the vicinity of 75 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program. 4 tabs

  20. Studies in iodine metabolism: Monitoring of animal thyroids: Final progress report, April 1983 through March 1987

    International Nuclear Information System (INIS)

    Van Middlesworth, L.

    1987-01-01

    This report contains the results of monitoring radioiodine and radiocesium levels in both domestic and wild animals. Included are thyroids of cattle and sheep before and after the Chernobyl accident, monitoring of thyroids from deer kills on the Oak Ridge Plantation and the Savannah River Reserve. (DT)

  1. NRC TLD Direct Radiation Monitoring Network progress report, October--December 1994. Volume 14, No. 4

    Energy Technology Data Exchange (ETDEWEB)

    Struckmeyer, R.

    1995-03-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1994. It provides the ambient radiation levels measured in the vicinity of 75 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program.

  2. NRC TLD Direct Radiation Monitoring Network. Progress report, October--December 1996

    International Nuclear Information System (INIS)

    Struckmeyer, R.

    1997-03-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1996. It provides the ambient radiation levels measured in the vicinity of 74 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program. 3 figs., 4 tabs

  3. NRC TLD Direct Radiation Monitoring Network progress report, October--December 1994. Volume 14, No. 4

    International Nuclear Information System (INIS)

    Struckmeyer, R.

    1995-03-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1994. It provides the ambient radiation levels measured in the vicinity of 75 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program

  4. NRC TLD Direct Radiation Monitoring Network. Progress report, October--December 1996

    Energy Technology Data Exchange (ETDEWEB)

    Struckmeyer, R.

    1997-03-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1996. It provides the ambient radiation levels measured in the vicinity of 74 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program. 3 figs., 4 tabs.

  5. Chronobiologically Interpreted Ambulatory Blood Pressure Monitoring in Health and Disease.

    Science.gov (United States)

    Halberg, Franz; Mult, Hc; Cornélissen, Germaine; Hillman, Dewayne; Beaty, Larry A; Hong, Shiyu; Schwartzkopff, Othild; Watanabe, Yoshihiko; Otsuka, Kuniaki; Siegelova, Jarmila

    2012-05-01

    To detect vascular variability anomalies (VVAs), a blood pressure and heart rate profile around the clock for at least 7 days is a start. As a minimum, measurement every 60 or preferably 30 minutes for a week is needed, to be continued if abnormality is found, to assess the about 24-hour (circadian) variability that exists in all individuals. As a first dividend, one then also obtains a glimpse of 2 of the very many longer-than-circadian periodicities, the biological half-week and week. Certainly if we can have sensors and computer chips in our cars that continuously monitor the pressure over a tire's life, we should be able to do the same job for ourselves for diagnostic and therapeutic decisions. Healthcare today emphasizes wellness with recommendations for exercise and a proper diet, yet these evaluations may not be adequate. BP may be measured at a visit to the doctor or before an exercise session, along with measuring body weight and performing a physical exam. The seeds of disease are planted long before they are visible, and what appears to be normal from a conventional point of view may in fact actually be abnormal. Hidden alterations of physiological function, masked by the body's remarkable adaptive capabilities, may become visible through a new diagnostic and therapeutic realm-chronobiology-that reveals hitherto unseen abnormalities. The tools of chronobiology may yield additional dividends, such as the detection of physiological "loads" related to stress and stress relief and the undesirable effcts of space weather upon personal events such as sudden cardiac death, societal events like terrorism and war, and natural disasters. Chronobiologi cally interpreted automatic ambulatory BP and heart rate (HR) monitoring (C-ABPM) may detect the antecedents of these types of events. C-ABPM is of interest in preventive cardiology, since it reveals new diagnoses as vascular variability anomalies (VVAs) and renders previous conventional diagnoses more reliable, such

  6. Research progress of on-line automatic monitoring of chemical oxygen demand (COD) of water

    Science.gov (United States)

    Cai, Youfa; Fu, Xing; Gao, Xiaolu; Li, Lianyin

    2018-02-01

    With the increasingly stricter control of pollutant emission in China, the on-line automatic monitoring of water quality is particularly urgent. The chemical oxygen demand (COD) is a comprehensive index to measure the contamination caused by organic matters, and thus it is taken as one important index of energy-saving and emission reduction in China’s “Twelve-Five” program. So far, the COD on-line automatic monitoring instrument has played an important role in the field of sewage monitoring. This paper reviews the existing methods to achieve on-line automatic monitoring of COD, and on the basis, points out the future trend of the COD on-line automatic monitoring instruments.

  7. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

  8. EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

    Directory of Open Access Journals (Sweden)

    David B. McGuigan

    2017-07-01

    Full Text Available Mutations in the EYS (eyes shut homolog gene are a common cause of autosomal recessive (ar retinitis pigmentosa (RP. Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT, and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit, some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

  9. The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

    Directory of Open Access Journals (Sweden)

    Jackalina M Van Kampen

    Full Text Available The development of effective neuroprotective therapies for Parkinson's disease (PD has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the

  10. Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hai-yang JIANG

    2017-10-01

    Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

  11. The role of hepatocyte nuclear factor 4 alpha in development and progression of liver diseases

    Directory of Open Access Journals (Sweden)

    YANG Jinlian

    2016-02-01

    Full Text Available Hepatocyte nuclear factor 4 alpha (HNF4α, a member of the nuclear receptor superfamily, has a high expression level in mature hepatocytes. HNF4α can regulate hepatocyte-specific gene expression at a transcriptional level, promote hepatocyte development and differentiation, participate in establishment and maintenance of hepatocyte polarity, and enhance the synthetic, metabolic, and detoxifying functions of the liver. Through inhibiting the activation of hepatic stellate cells, reversing epithelial-mesenchymal transition, and inhibiting the proliferation, invasion, and metastasis of hepatoma cells, HNF4α may be involved in the development and progression of various liver diseases including liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. This paper elaborates on the biological functions of HNF4α, and summarizes and analyzes the research advances in the mechanisms of action of HNF4α in the pathological process of liver diseases, in order to provide references for further investigation of the potential targeted therapies for liver diseases.

  12. Klinefelter′s syndrome associated with progressive muscular atrophy simulating Kennedy′s disease

    Directory of Open Access Journals (Sweden)

    Pedro Enrique Jiménez Caballero

    2012-01-01

    Full Text Available Kennedy′s disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter′s syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klinefelter′s syndrome. Genetic study of Kennedy′s disease was normal. Our patient differs from those with Kennedy′s disease in the absence of bulbar and sensory symptoms. It is suggested that the X chromosome plays an important role in the biology of motor neurons.

  13. Latest progress of BIGH3 gene in corneal diseases and diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Fan-Qian Song

    2017-03-01

    Full Text Available BIGH3 gene plays an important role in ocular diseases. On the one hand, it is closely related to the occurrence of corneal diseases. BIGH3 gene can inhibit corneal neovascularization, lead to corneal dystrophy, participate in keratoconus formation. On the other hand, it can lead to the formation of neovascularization in diabetic retinopathy. The latest experiments show that TGF beta secreted by macrophages can promote the expression of BIGH3 mRNA and BIGH3 protein, and promote apoptosis of retinal endothelial cells and pericytes, which leads to the formation of neovascularization in diabetic retinopathy. This article will describe the new progress of BIGH3 gene in ocular diseases from several aspects as mentioned above.

  14. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Nielsen, Lotte B; Andersen, Marie-Louise

    2016-01-01

    Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type...... 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several...

  15. [Retrospective analysis of influence of differential protein intake on renal prognosis for progressive chronic kidney disease].

    Science.gov (United States)

    Dai, Wendi; Yin, Daoxin; Cui, Wenying; Liu, Wenhu

    2014-01-28

    To explore retrospectively the influence of differential protein intake on renal prognosis for progressive chronic kidney disease (CKD). A total of 159 chronic kidney disease patients at stages 2, 3 and 4 were enrolled and a questionnaire survey was conducted from January 2009 to July 2012. They were followed monthly and their clinical data collected, including primary disease, blood pressure, body mass index and adverse events. Laboratory tests were performed every 3 months, including biochemical parameters, protein-energy malnutrition (PEM), diet reviews and daily protein intake (DPI). A simplified MDRD formula was employed to evaluate the level of estimated glomerular filtration rate (eGFR). According to the level of DPI, they were divided into 3 groups of very low protein diet (VLPD): DPI ≤ 0.6 g · kg(-1) · d(-1), low-protein diet (LPD): DPI >0.6-protein diet (NPD): DPI ≥ 0.8 · g · kg(-1) · d(-1). Among them, 4 cases (2.50%) progressed to uremia stage and received renal replacement therapy, 2(1.25%) experienced rapid decline in renal function, 9(5.66%) were hospitalized from cardio-cerebral diseases and the 2-year kidney survival rate was 97.5%. At the end of study, among 9 patients of PEM, 2 subjects had a serum level of albumin under 32 g/L and another 7 with a BMI 0.05). Within a certain range, differential protein intake may not significantly affect the prognosis of kidney for progressive CKD patients.

  16. The role of nanotechnology and nano and micro-electronics in monitoring and control of cardiovascular diseases and neurological disorders

    Science.gov (United States)

    Varadan, Vijay K.

    2007-04-01

    controlled manipulation of individual molecules and atoms that can interact with the human body at sub-cellular level. The recent progress in microelectronics and nanosensors crates very powerful tools for the early detection and diagnosis. The nanowire integrated potassium and dopamine sensors are ideal for the monitoring and control of many cardiovascular diseases and neurological disorders. Selected movies illustrating the applications of nanodevices to patients will be shown at the talk.

  17. PROGRESSIVE MUSCLE RELAXATION INCREASE PEAK EXPIRATORY FLOW RATE ON CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS

    Directory of Open Access Journals (Sweden)

    Tintin Sukartini

    2017-07-01

    Full Text Available Introduction: Limited progressive air flow in Chronic Obstructive Pulmonary Disease (COPD can caused by small airway disease (bronchiolitis obstructive and loss of elasticity of the lung (emphysema. Further it can be decreasing the quality of life in COPD patients because dyspnea and uncomfortable in activity. Progressive muscle relaxation (PMR is one of the relaxation technique that can repair pulmonary ventilation by decreasing chronic constriction of the respiratory muscles. The objective of this study was to analyze the effect of progressive muscle relaxation on raised peak expiratory flow rate (PEFR. Method: A pre-experimental one group pre-post test design was used in this study. Population was all of the COPD patients at Pulmonary Specialist Polyclinic Dr Mohamad Soewandhie Surabaya. There were 8 respondents taken by using purposive sampling. PEFR was counted by using peak flow meter every six day. Data were analyzed by using Paired t-Test with significance level  p≤0.05. Result: The result showed that PMR had significance level on increasing of PEFR (p=0.012. Discussion: It can be concluded that PMR has an effect on raise PEFR. Further studies are recommended to measure the effect of PMR on respiratory rate (RR, heart rate (HR subjective dyspnoe symptoms, forced expiration volume on the first minute (FEV1 and mid maximum flow rate (MMFR in COPD patients.

  18. Progression of regional neuropathology in Alzheimer disease and normal elderly: findings from the Nun study.

    Science.gov (United States)

    Wolf, D S; Gearing, M; Snowdon, D A; Mori, H; Markesbery, W R; Mirra, S S

    1999-01-01

    Although diffuse plaques in the neocortex may represent an early stage in the evolution of neuritic plaques, plaques in the striatum and cerebellum retain their predominantly diffuse nature in Alzheimer disease (AD), regardless of disease duration. We had the opportunity to explore the progression of these regional features by using autopsy brain specimens from 15 cognitively normal and five AD subjects, all Catholic sisters enrolled in the Nun Study, a longitudinal study on aging and AD. Neuropathologic changes were assessed in the temporal cortex, striatum, and cerebellum without knowledge of clinical status. We found diffuse plaques in the striatum in six (40%) and cerebellar plaques in none of the brains from the non-demented subjects. Striatal plaques were present in all five and cerebellar plaques in four of the five AD cases. In the 20 cases overall, the presence of striatal plaques generally paralleled the occurrence of neuritic plaques in neocortex and correlated with lower scores on several neuropsychologic tests assessing memory. Our findings suggest that striatal diffuse plaques occur relatively early in the progression of AD pathology and coincide with neocortical pathology and cognitive changes. Thus, it is unlikely that temporal factors alone account for regional differences in progression of AD neuropathology.

  19. Triple pelvic osteotomy: effect on limb function and progression of degenerative joint disease

    International Nuclear Information System (INIS)

    Johnson, A.L.; Smith, C.W.; Pijanowski, G.J.; Hungerford, L.L.

    1998-01-01

    The objective of this study was to evaluate prospectively the outcome of 21 clinical patients treated with triple pelvic osteotomies during the year following surgery. Specific aims included documenting the time of and extent of improved limb function as measured by force plate analysis, evaluating the progression of degenerative joint disease (DJD) in the treated and untreated coxofemoral joints, and determining whether or not triple pelvic osteotomy resulted in degenerative joint changes in the ipsilateral stifle and hock. Twelve dogs were treated unilaterally and nine dogs were treated bilaterally with triple pelvic osteotomies. There were no differences in mean anteversion angles, angles of inclination, or preoperative DJD between treated hips and untreated hips. Degenerative joint disease progressed significantly in all hips regardless of treatment. Two cases developed hyperextension of their hocks after the triple pelvic osteotomies. However, no radiographic evidence of DJD was observed for any of the stifles or hocks at any observation time. A significant increase in vertical peak force (VPF) scores was noted for treated legs by two-to-three months after surgery, which continued over time. Untreated legs did not show a significant change in VPF scores over time. No differences were found in progression to higher scores when unilaterally treated legs, first-side treated legs, and second-side treated legs were compared

  20. The Role of Dendritic Cells in Fibrosis Progression in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Paloma Almeda-Valdes

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most frequent cause of chronic liver disease. NAFLD encompasses a wide range of pathologies, from simple steatosis to steatosis with inflammation to fibrosis. The pathogenesis of NAFLD progression has not been completely elucidated, and different liver cells could be implicated. This review focuses on the current evidence of the role of liver dendritic cells (DCs in the progression from NAFLD to fibrosis. Liver DCs are a heterogeneous population of hepatic antigen-presenting cells; their main function is to induce T-cell mediated immunity by antigen processing and presentation to T cells. During the steady state liver DCs are immature and tolerogenic. However, in an environment of chronic inflammation, DCs are transformed to potent inducers of immune responses. There is evidence about the role of DC in liver fibrosis, but it is not clearly understood. Interestingly, there might be a link between lipid metabolism and DC function, suggesting that immunogenic DCs are associated with liver lipid storage, representing a possible pathophysiological mechanism in NAFLD development. A better understanding of the interaction between inflammatory pathways and the different cell types and the effect on the progression of NAFLD is of great relevance.

  1. Research progress in role of iron overload in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    LI Guangming

    2013-12-01

    Full Text Available Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD. The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iron overload and lipid metabolism, and relationship between type of iron deposition and liver damage; the significance of iron overload in the diagnosis and treatment of NAFLD is discussed from iron overload as a new marker of risk stratification and potential therapeutic target in NAFLD. It is currently considered that iron overload, whether the cause or result of NAFLD progression, will promote the progression of NAFLD once it occurs; as a new marker of risk stratification and potential therapeutic target in NAFLD, iron load is worthy of further study.

  2. NRC TLD [thermoluminescent dosimeter] Direct Radiation Monitoring Network: Progress report, January-March 1988

    International Nuclear Information System (INIS)

    Struckmeyer, R.; McNamara, N.

    1988-06-01

    This report provides the status and results of the NRC Thermoluminescent Dosimeter (TLD) Direct Radiation Monitoring Network. It presents the radiation levels measured in the vicinity of NRC licensed facility sites throughout the country for the first quarter of 1988

  3. NRC TLD direct radiation monitoring network: Progress report, April--June 1988

    International Nuclear Information System (INIS)

    Struckmeyer, R.; McNamara, N.

    1988-09-01

    This report provides the status and results of the NRC Thermoluminescent Dosimeter (TLD) Direct Radiation Monitoring Network. It presents the radiation levels measured in the vicinity of NRC licensed facility sites throughout the country for the second quarter of 1988

  4. 15. Internal symposium on recent progress of nondestructive inspection and monitoring technologies for nuclear power plants

    International Nuclear Information System (INIS)

    1994-01-01

    At the symposium, lectures were given on the recent development of the nondestructive inspection technology for nuclear power plants, the trend regarding the nondestructive inspection in foreign countries (Japan-Germany atomic energy seminar), the present state and subjects of the monitoring technology in BWR plants, the present state and subjects of the monitoring technology in PWR plants, and the present state and the subjects for hereafter of the defect evaluation method in the equipment of light water reactors. The data on the ultrasonic flaw detection in aluminum alloy welded joints were obtained. The German inspection technology is similar to that in Japan and other countries. The research on the plant synthetic monitoring and diagnosis system is reported. The monitoring systems for abnormal state in operation, troubles and the secular change of equipment are reported. The evaluation of the flaws in nuclear piping is reported. The summaries of the lectures are collected in this book. (K.I.)

  5. A computational method for computing an Alzheimer’s Disease Progression Score; experiments and validation with the ADNI dataset

    Science.gov (United States)

    Jedynak, Bruno M.; Liu, Bo; Lang, Andrew; Gel, Yulia; Prince, Jerry L.

    2014-01-01

    Understanding the time-dependent changes of biomarkers related to Alzheimer’s disease (AD) is a key to assessing disease progression and to measuring the outcomes of disease-modifying therapies. In this paper, we validate an Alzheimer’s disease progression score model which uses multiple biomarkers to quantify the AD progression of subjects following three assumptions: (1) there is a unique disease progression for all subjects, (2) each subject has a different age of onset and rate of progression, and (3) each biomarker is sigmoidal as a function of disease progression. Fitting the parameters of this model is a challenging problem which we approach using an alternating least squares optimization algorithm. In order to validate this optimization scheme under realistic conditions, we use the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. With the help of Monte Carlo simulations, we show that most of the global parameters of the model are tightly estimated, thus enabling an ordering of the biomarkers that fit the model well, ordered as: the Rey auditory verbal learning test with 30 minutes delay, the sum of the two lateral hippocampal volumes divided by the intra-cranial volume, followed by (the clinical dementia rating sum of boxes score and the mini mental state examination score) in no particular order and lastly the Alzheimer’s disease assessment scale-cognitive subscale. PMID:25444605

  6. National rural drinking water monitoring: progress and challenges with India's IMIS database

    OpenAIRE

    Wescoat, James; Fletcher, Sarah Marie; Novellino, Marianna

    2015-01-01

    National drinking water programs seek to address monitoring challenges that include self-reporting, data sampling, data consistency and quality, and sufficient frequency to assess the sustainability of water systems. India stands out for its comprehensive rural water database known as Integrated Management Information System (IMIS), which conducts annual monitoring of drinking water coverage, water quality, and related program components from the habitation level to the district, state, and n...

  7. Progress on health physics monitoring systems at the French Atomic Energy Commission

    International Nuclear Information System (INIS)

    Grimont, B.; Joffre, H.; Leblanc, P.

    1977-01-01

    The need for health physics protection on nuclear plants or laboratory (nuclear power plant, fuel processing plant, etc) leads to data measurement and monitoring centralisation. This paper reviews the systems used for that purpose: old monobloc electronic systems, mini computer system, recent microprocessor-based system, it shows the impact of new methods on the system performances : standardization of measurements and alarms level for irradiation and contamination, reliability, peripherals devices (typewriters, CRT) availability for easy and efficient monitoring, and hardware compactness [fr

  8. Evaluation and monitoring of wild/natural steelhead trout production: project progress report, 1996; ANNUAL

    International Nuclear Information System (INIS)

    Leth, Brian D.; Holubetz, Terry; Nemeth, Doug

    2000-01-01

    This project was initiated to provide additional, and more definitive, information regarding wild steelhead Oncorhynchus mykiss populations in Idaho. Important streams for wild steelhead production were identified and selected for monitoring. Monitoring activities employed among streams varied, but generally included: aerial redd counts, placement of adult weirs, enumeration of juveniles through mask and snorkel counts, and emigrant trapping. This report details activities during the 1996 field season

  9. Role of the intrarenal renin-angiotensin system in the progression of renal disease.

    Science.gov (United States)

    Urushihara, Maki; Kagami, Shoji

    2017-09-01

    The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

  10. Radiological air monitoring and sample analysis research and development progress report

    International Nuclear Information System (INIS)

    1992-01-01

    Sponsored by a Department Of Energy (DOE) research and development grant, the State of Idaho INEL Oversight Program (OP) personnel designed an independent air monitoring system that provides detection of the presence of priority airborne contaminants potentially migrating beyond INEL boundaries. Initial locations for off-site ambient air monitoring stations were chosen in consultation with: DOE and NOAA reports; Mesodif modeling; review of the relevant literature; and communication with private contractors and experts in pertinent fields. Idaho State University (ISU) has initiated an Environmental Monitoring Program (EMP). The EMP provides an independent monitoring function as well as a training ground for students. Students learn research techniques dedicated to environmental studies and learn analytical skills and rules of compliance related to monitoring. ISU-EMP assisted OP in specific aspects of identifying optimum permanent monitoring station locations, and in selecting appropriate sample collection equipment for each station. The authorization to establish, prepare and install sampling devices on selected sites was obtained by OP personnel in conjunction with ISU-EMP personnel. All samples described in this program are collected by OP or ISU-EMP personnel and returned to the ISU for analysis. This report represents the summary of results of those samples collected and analyzed for radioactivity during the year of 1992

  11. Genetic Alzheimer Disease and Sporadic Dementia With Lewy Bodies: A Comorbidity Presenting as Primary Progressive Aphasia.

    Science.gov (United States)

    Picková, Tereza; Matěj, Radoslav; Bezdicek, Ondrej; Keller, Jiří; van der Zee, Julie; Van Broeckhoven, Christine; Cséfalvay, Zsolt; Rusina, Robert

    2017-03-01

    We report a 44-year-old woman, with a family history of early-onset dementia, presenting with primary progressive aphasia. This clinically variable syndrome has multiple underlying pathologies, and correlations between clinical manifestations and postmortem neuropathologic findings are controversial. Our patient suffered worsening language impairment with major word-finding difficulties but preserved comprehension. She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes. Magnetic resonance imaging showed early left perisylvian and bitemporal atrophy. The patient died shortly afterward from colon cancer. Neuropathologic examination revealed advanced early-onset Alzheimer and Lewy body disease, plus a clinically nonrelevant metastasis of her colon cancer in her left parietal lobe. Genetic examination revealed a p.Glu184Asp mutation in the presenilin1 gene. Our findings confirm the importance of a thorough appreciation for the clinical and neuropathologic correlations in patients with atypical neurodegenerative dementias.

  12. Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

    Science.gov (United States)

    Chonchol, Michel; Gitomer, Berenice; Isakova, Tamara; Cai, Xuan; Salusky, Isidro; Pereira, Renata; Abebe, Kaleab; Torres, Vicente; Steinman, Theodor I; Grantham, Jared J; Chapman, Arlene B; Schrier, Robert W; Wolf, Myles

    2017-09-07

    Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in the HALT-PKD Study A ( n =540; mean eGFR =91±17 ml/min per 1.73 m 2 ) and B ( n =462; mean eGFR =48±12 ml/min per 1.73 m 2 ). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in height-adjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Median (interquartile range) intact fibroblast growth factor 23 was 44 (33-56) pg/ml in HALT-PKD Study A and 69 (50-93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, -3.62; 95% confidence interval, -4.12 to -3.12 versus quartile 1, -2.51; 95% confidence interval, -2.71 to -2.30 ml/min per 1.73 m 2 ; P for trend kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m 2 did not improve risk prediction. Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially

  13. Risk factors for the progression of periodontal disease in a Greek adult population.

    Science.gov (United States)

    Chrysanthakopoulos, Nikolaos A

    2017-05-01

    The purpose of the present study was to investigate the progression risk factors of periodontal disease by individual characteristics at baseline in a Greek adult population. The study sample consisted of 854 individuals. All participants were clinically examined and answered questions regarding sex, smoking status, socioeconomic status, low educational level, frequency of dental follow up, and oral hygiene habits. Serum levels of disease markers were investigated, and attachment levels were clinically recorded. For the assessment of periodontal disease progression, additional clinical attachment loss (CAL) was used if one or more sites showed a 3 mm or more increase in probing attachment level over a 2-year period. Statistical analysis was performed by using a modified multiple Poisson's analysis model. A total of 74% of the participants exhibited additional CAL over a 2-year period. Significant associations were observed between additional CAL and smoking (relative risk [RR] = 0.78, 95% confidence level [CI] = 0.65-0.92), attachment level of 5 mm or more at baseline (RR = 0.89, 95% CI = 0.75-1.05), educational level (RR = 0.90, 95% CI = 0.76-1.07), socioeconomic status (RR = 0.86, 95% CI = 0.59-1.14), and irregular dental follow up (RR = 1.23, 95% CI = 1.04-1.45). Smoking, baseline attachment level of 5 mm or more, low educational level, low socioeconomic status, and irregular dental follow up could be considered risk factors for further CAL. © 2015 Wiley Publishing Asia Pty Ltd.

  14. Dietary Energy Density, Renal Function, and Progression of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Rouhani

    2016-01-01

    Full Text Available Background. There is evidence of the association between dietary energy density and chronic diseases. However, no report exists regarding the relation between DED and chronic kidney disease (CKD. Objective. To examine the association between dietary energy density (DED, renal function, and progression of chronic kidney disease (CKD. Design. Cross-sectional. Setting. Three nephrology clinics. Subjects. Two hundred twenty-one subjects with diagnosed CKD. Main Outcome Measure. Dietary intake of patients was assessed by a validated food frequency questionnaire. DED (in kcal/g was calculated with the use of energy content and weight of solid foods and energy yielding beverages. Renal function was measured by blood urea nitrogen (BUN, serum creatinine (Cr, and estimated glomerular filtration rate (eGFR. Results. Patients in the first tertile of DED consumed more amounts of carbohydrate, dietary fiber, potassium, phosphorus, zinc, magnesium, calcium, folate, vitamin C, and vitamin B2. After adjusting for confounders, we could not find any significant trend for BUN and Cr across tertiles of DED. In multivariate model, an increased risk of being in the higher stage of CKD was found among those in the last tertile of DED (OR: 3.15; 95% CI: 1.30, 7.63; P=0.01. Conclusion. We observed that lower DED was associated with better nutrient intake and lower risk of CKD progression.

  15. Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Marion Ortner

    2016-09-01

    Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

  16. Monitoring of anticoagulant therapy in heart disease: considerations for the current assays.

    Science.gov (United States)

    Boroumand, Mohammadali; Goodarzynejad, Hamidreza

    2010-01-01

    Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio (INR) was introduced to "normalize" all PT reagents to a World Health Organization (WHO) reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists (VKAs) (i.e., at least 6 weeks of VKA therapy), and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation

  17. Unsupervised progressive elastic band exercises for frail geriatric inpatients objectively monitored by new exercise-integrated technology

    DEFF Research Database (Denmark)

    Rathleff, Camilla Rams; Bandholm, T.; Spaich, Erika Geraldina

    2017-01-01

    the amount of supervised training, and unsupervised training could possibly supplement supervised training thereby increasing the total exercise dose during admission. A new valid and reliable technology, the BandCizer, objectively measures the exact training dosage performed. The purpose was to investigate...... feasibility and acceptability of an unsupervised progressive strength training intervention monitored by BandCizer for frail geriatric inpatients. Methods: This feasibility trial included 15 frail inpatients at a geriatric ward. At hospitalization, the patients were prescribed two elastic band exercises...... of 2-min pauses and a time-under-tension of 8 s. The feasibility criterion for the unsupervised progressive exercises was that 33% of the recommended number of sets would be performed by at least 30% of patients. In addition, patients and staff were interviewed about their experiences...

  18. A Framework for (Tele-) Monitoring of the Rehabilitation Progress in Stroke Patients: eHealth 2015 Special Issue.

    Science.gov (United States)

    Jagos, H; David, V; Haller, M; Kotzian, S; Hofmann, M; Schlossarek, S; Eichholzer, K; Winkler, M; Frohner, M; Reichel, M; Mayr, W; Rafolt, D

    2015-01-01

    Preservation of mobility in conjunction with an independent life style is one of the major goals of rehabilitation after stroke. The Rehab@Home framework shall support the continuation of rehabilitation at home. The framework consists of instrumented insoles, connected wirelessly to a 3G ready tablet PC, a server, and a web-interface for medical experts. The rehabilitation progress is estimated via automated analysis of movement data from standardized assessment tests which are designed according to the needs of stroke patients and executed via the tablet PC application. The Rehab@Home framework's implementation is finished and ready for the field trial (at five patients' homes). Initial testing of the automated evaluation of the standardized mobility tests shows reproducible results. Therefore it is assumed that the Rehab@Home framework is applicable as monitoring tool for the gait rehabilitation progress in stroke patients.

  19. An Evaluation of the Word Triad Method for Monitoring Spelling Progress

    Science.gov (United States)

    Frisby, Craig; Wang, Ze

    2018-01-01

    Although spelling skill progress has typically been studied within the context of students' responses to written story starters (Deno, Marsten, & Mirkin, 1982; Fuchs & Fuchs, 2011; Hosp, Hosp, & Howell, 2007; Shinn & Shinn, 2002), there has been little research conducted within a curriculum-based measurement framework that has…

  20. Studies in iodine metabolism: monitoring of animal thyroids. Progress report, 1984-1985

    International Nuclear Information System (INIS)

    Van Middlesworth, L.

    1986-01-01

    This progress report briefly summarizes the counting and re-counting of domestic or wild animal thyroids from the United Kingdom, Federal Republic of Germany, the reservation of the Savannah River Plant, or from the DOE reservation at Oak Ridge. The possible effect that a mycotoxin may have an iodine deficiency was investigated. 3 refs., 3 figs., 4 tabs. (DT)

  1. Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles.

    Directory of Open Access Journals (Sweden)

    Raquel Pinho

    Full Text Available The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson's disease (PD progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression

  2. Regional Cerebral Disease Progression in Friedreich's Ataxia: A Longitudinal Diffusion Tensor Imaging Study.

    Science.gov (United States)

    Mascalchi, Mario; Toschi, Nicola; Giannelli, Marco; Ginestroni, Andrea; Della Nave, Riccardo; Tessa, Carlo; Piacentini, Silvia; Dotti, Maria Teresa; Aiello, Marco; Nicolai, Emanuele; Soricelli, Andrea; Salvi, Fabrizio; Diciotti, Stefano

    2016-01-01

    Imaging biomarkers of disease progression are desirable in inherited ataxias. MRI has demonstrated brain damage in Friedreich ataxia (FRDA) in form of regional atrophy of the medulla, peridentate cerebellar white matter (WM) and superior cerebellar peduncles (visible in T1-weighted images) and of change of microstructural characteristics of WM tracts of the brainstem, cerebellar peduncles, cerebellum, and supratentorial structures (visible through diffusion-weighted imaging). We explored the potential of brain MR morphometry and diffusion tensor imaging (DTI) to track the progression of neurodegeneration in FRDA. Eight patients (5F, 3M; age 13.4-41.2 years) and 8 healthy controls (2F, 6M; age 26.2-48.3 years) underwent 2 MRI examinations (mean 3.9 and 4.1 years apart, respectively) on the same 1.5T scanner. The protocol included 3D T1-weighted images and axial diffusion-weighted images (b-value 1,000 s/mm(2)) for calculating maps of fractional anisotropy, mean, axial and radial diffusivity, and mode of anisotropy. Tensor-based morphometry was used to investigate regional volume changes and tract-based spatial statistics was used to investigate microstructural changes in WM tracts. Longitudinal analyses showed no differences in regional volume changes but a significant difference in axial diffusivity changes in cerebral and corpus callosum WM of patients as compared to controls (mean longitudinal rate of change for axial diffusivity: -.02 × 10(-3) mm(2)/s/year in patients vs. .01 × 10(-3) mm(2)/s/year in controls). No correlation with number of triplets, disease duration, and worsening of the clinical deficit was observed. DTI can track brain microstructural changes in FRDA and can be considered a potential biomarker of disease progression. Copyright © 2015 by the American Society of Neuroimaging.

  3. Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies

    Science.gov (United States)

    Pircher, Andreas; Jöhrer, Karin; Kocher, Florian; Steiner, Normann; Graziadei, Ivo; Heidegger, Isabel; Pichler, Renate; Leonhartsberger, Nicolai; Kremser, Christian; Kern, Johann; Untergasser, Gerold; Gunsilius, Eberhard; Hilbe, Wolfgang

    2016-01-01

    Numerous antiangiogenic agents are approved for the treatment of oncological diseases. However, almost all patients develop evasive resistance mechanisms against antiangiogenic therapies. Currently no predictive biomarker for therapy resistance or response has been established. Therefore, the aim of our study was to identify biomarkers predicting the development of therapy resistance in patients with hepatocellular cancer (n = 11), renal cell cancer (n = 7) and non-small cell lung cancer (n = 2). Thereby we measured levels of angiogenic growth factors, tumor perfusion, circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP) and tumor endothelial markers (TEM) in patients during the course of therapy with antiangiogenic agents, and correlated them with the time to antiangiogenic progression (aTTP). Importantly, at disease progression, we observed an increase of proangiogenic factors, upregulation of CEC/CEP levels and downregulation of TEMs, such as Robo4 and endothelial cell-specific chemotaxis regulator (ECSCR), reflecting the formation of torturous tumor vessels. Increased TEM expression levels tended to correlate with prolonged aTTP (ECSCR high = 275 days vs. ECSCR low = 92.5 days; p = 0.07 and for Robo4 high = 387 days vs. Robo4 low = 90.0 days; p = 0.08). This indicates that loss of vascular stabilization factors aggravates the development of antiangiogenic resistance. Thus, our observations confirm that CEP/CEC populations, proangiogenic cytokines and TEMs contribute to evasive resistance in antiangiogenic treated patients. Higher TEM expression during disease progression may have clinical and pathophysiological implications, however, validation of our results is warranted for further biomarker development. PMID:26956051

  4. Characterization of LEDGF/p75 genetic variants and association with HIV-1 disease progression.

    Directory of Open Access Journals (Sweden)

    Peter Messiaen

    Full Text Available BACKGROUND: As Lens epithelium-derived growth factor (LEDGF/p75 is an important co-factor involved in HIV-1 integration, the LEDGF/p75-IN interaction is a promising target for the new class of allosteric HIV integrase inhibitors (LEDGINs. Few data are available on the genetic variability of LEDGF/p75 and the influence on HIV disease in vivo. This study evaluated the relation between LEDGF/p75 genetic variation, mRNA expression and HIV-1 disease progression in order to guide future clinical use of LEDGINs. METHODS: Samples were derived from a therapy-naïve cohort at Ghent University Hospital and a Spanish long-term-non-progressor cohort. High-resolution melting curve analysis and Sanger sequencing were used to identify all single nucleotide polymorphisms (SNPs in the coding region, flanking intronic regions and full 3'UTR of LEDGF/p75. In addition, two intronic tagSNPs were screened based on previous indication of influencing HIV disease. LEDGF/p75 mRNA was quantified in patient peripheral blood mononuclear cells (PBMC using RT-qPCR. RESULTS: 325 samples were investigated from patients of Caucasian (n = 291 and African (n = 34 origin, including Elite (n = 49 and Viremic controllers (n = 62. 21 SNPs were identified, comprising five in the coding region and 16 in the non-coding regions and 3'UTR. The variants in the coding region were infrequent and had no major impact on protein structure according to SIFT and PolyPhen score. One intronic SNP (rs2737828 was significantly under-represented in Caucasian patients (P<0.0001 compared to healthy controls (HapMap. Two SNPs showed a non-significant trend towards association with slower disease progression but not with LEDGF/p75 expression. The observed variation in LEDGF/p75 expression was not correlated with disease progression. CONCLUSIONS: LEDGF/p75 is a highly conserved protein. Two non-coding polymorphisms were identified indicating a correlation with disease outcome, but further

  5. Data-driven models of dominantly-inherited Alzheimer's disease progression.

    Science.gov (United States)

    Oxtoby, Neil P; Young, Alexandra L; Cash, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Bateman, Randall J; Fox, Nick C; Schott, Jonathan M; Alexander, Daniel C

    2018-03-22

    Dominantly-inherited Alzheimer's disease is widely hoped to hold the key to developing interventions for sporadic late onset Alzheimer's disease. We use emerging techniques in generative data-driven disease progression modelling to characterize dominantly-inherited Alzheimer's disease progression with unprecedented resolution, and without relying upon familial estimates of years until symptom onset. We retrospectively analysed biomarker data from the sixth data freeze of the Dominantly Inherited Alzheimer Network observational study, including measures of amyloid proteins and neurofibrillary tangles in the brain, regional brain volumes and cortical thicknesses, brain glucose hypometabolism, and cognitive performance from the Mini-Mental State Examination (all adjusted for age, years of education, sex, and head size, as appropriate). Data included 338 participants with known mutation status (211 mutation carriers in three subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to four visits each, 1.1 ± 1.9 years in duration; spanning 30 years before, to 21 years after, parental age of symptom onset). We used an event-based model to estimate sequences of biomarker changes from baseline data across disease subtypes (mutation groups), and a differential equation model to estimate biomarker trajectories from longitudinal data (up to 66 mutation carriers, all subtypes combined). The two models concur that biomarker abnormality proceeds as follows: amyloid deposition in cortical then subcortical regions (∼24 ± 11 years before onset); phosphorylated tau (17 ± 8 years), tau and amyloid-β changes in cerebrospinal fluid; neurodegeneration first in the putamen and nucleus accumbens (up to 6 ± 2 years); then cognitive decline (7 ± 6 years), cerebral hypometabolism (4 ± 4 years), and further regional neurodegeneration. Our models predicted symptom onset more accurately than predictions that used familial estimates: root mean squared error of 1

  6. Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review.

    Directory of Open Access Journals (Sweden)

    Jan-Patrick Stellmann

    Full Text Available New agents with neuroprotective or neuroregenerative potential might be explored in primary-progressive Multiple Sclerosis (PPMS--the MS disease course with leading neurodegenerative pathology. Identification of patients with a high short-term risk for progression may minimize study duration and sample size. Cohort studies reported several variables as predictors of EDSS disability progression but findings were partially contradictory.To analyse the impact of published predictors on EDSS disease progression in a large cohort of PPMS patients.A systematic literature research was performed to identify predictors for disease progression in PPMS. Individual case data from the Sylvia Lawry Centre (SLC and the Hamburg MS patient database (HAPIMS was pooled for a retrospective validation of these predictors on the annualized EDSS change.The systematic literature analysis revealed heterogeneous data from 3 prospective and 5 retrospective natural history cohort studies. Age at onset, gender, type of first symptoms and early EDSS changes were available for validation. Our pooled cohort of 597 PPMS patients (54% female had a mean follow-up of 4.4 years and mean change of EDSS of 0.35 per year based on 2503 EDSS assessments. There was no significant association between the investigated variables and the EDSS-change.None of the analysed variables were predictive for the disease progression measured by the annualized EDSS change. Whether PPMS is still unpredictable or our results may be due to limitations of cohort assessments or selection of predictors cannot be answered. Large systematic prospective studies with new endpoints are needed.

  7. Urine liver fatty acid binding protein and chronic kidney disease progression

    DEFF Research Database (Denmark)

    Khatir, Dinah S; Bendtsen, Mette D; Birn, Henrik

    2017-01-01

    , regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61 ± 13 years) were included. Glomerular filtration ratio (GFR, 51Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L......Excretion of the tubular protein liver fatty acid binding protein (L-FABP) is a potential novel biomarker of renal dysfunction. We examined whether urine L-FABP excretion adds prognostic information to the well-established risk markers, blood pressure (BP), albumin excretion and baseline GFR...

  8. The Preclinical Research Progress of Stem Cells Therapy in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-01-01

    Full Text Available Parkinson’s disease (PD is a type of degenerative disorder of the basal ganglia, causing tremor at rest, muscle rigidity hypokinesia, and dementia. The effectiveness of drug treatments gradually diminishes because the conversion to dopamine within the brain is increasingly disrupted by the progressive degeneration of the dopaminergic terminals. After long-term treatment, most patients with PD suffer from disability that cannot be satisfactorily controlled. To solve these issues, stem cells have recently been used for cell therapy of PD. In this review, the characteristics of different stem cells and their therapeutic effects on PD treatment will be discussed.

  9. Yucca Mountain Biological Resources Monitoring Program. Progress report, October 1992--December 1993

    International Nuclear Information System (INIS)

    1994-05-01

    The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of (as amended in 1987) to study and characterize the suitability of Yucca Mountain as a potential geologic repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a potential repository. To ensure that site characterization activities do not adversely affect the environment at Yucca Mountain, a program has been implemented to monitor and mitigate potential impacts and ensure activities comply with applicable environmental regulations. This report describes the activities and accomplishments of EG ampersand G Energy Measurements, Inc. (EG ampersand G/EM) from October 1992 through December 1993 for six program areas within the Terrestrial Ecosystem component of the environmental program for the Yucca Mountain Site Characterization Project (YMP): Site Characterization Effects, Desert Tortoises (Gopherus agassizii), Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support

  10. Monitoring diseases based on register data: Methods and application in the Danish swine production

    DEFF Research Database (Denmark)

    Lopes Antunes, Ana Carolina

    The spread of diseases is one of the most important threats to animal production and public health. Disease spread causes considerable economic losses for the agricultural sector and constitutes trade-limiting factors, as transmission to countries free from disease should beavoided. Monitoring...

  11. Clinical monitoring of tooth wear progression in patients over a period of one year using CAD/CAM

    OpenAIRE

    Ahmed, Khaled E.; Whitters, John; Ju, Xiangyang; Pierce, S. Gareth; MacLeod, Charles N.; Murray, Colin A.

    2017-01-01

    Purpose: The aim of this study was to clinically monitor the progression of tooth wear over a period of 1 year in a cohort of referred tooth wear patients through the use of a computer-aided design/ computer-assisted manufacture (CAD/CAM) scanner and a standardized scanning/assessment methodology. Materials and Methods: Polyether impressions were made of 11 participants (130 teeth) at baseline and at 1 year. Impressions were poured in type IV dental stone and the anterior teeth were 3D scanne...

  12. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Irina T Zaharieva

    Full Text Available Duchenne muscular Dystrophy (DMD is an inherited disease caused by mutations in the dystrophin gene that disrupt the open reading frame, while in frame mutations result in Becker muscular dystrophy (BMD. Ullrich congenital muscular dystrophy (UCMD is due to mutations affecting collagen VI genes. Specific muscle miRNAs (dystromirs are potential non-invasive biomarkers for monitoring the outcome of therapeutic interventions and disease progression. We quantified miR-1, miR-133a,b, miR-206 and miR-31 in serum from patients with DMD, BMD, UCMD and healthy controls. MiR-1, miR-133a,b and miR-206 were upregulated in DMD, but unchanged in UCMD compared to controls. Milder DMD patients had higher levels of dystromirs than more severely affected patients. Patients with low forced vital capacity (FVC values, indicating respiratory muscle weakness, had low levels of serum miR-1 and miR-133b. There was no significant difference in the level of the dystromirs in BMD compared to controls. We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene. The dystromirs were also analysed in muscle biopsies of DMD patients included in a single dose intramuscular eteplirsen clinical trial. Our analysis detected a trend towards normalization of these miRNA between the pre- and post-treatment samples of the systemic trial, which however failed to reach statistical significance. This could possibly be due to the small number of patients and the short duration of these clinical trials. Although longer term studies are needed to clarify the relationship between dystrophin restoration following therapeutic intervention and the level of circulating miRNAs, our results indicate that miR-1 and miR-133 can be considered as exploratory biomarkers for monitoring the progression of muscle weakness

  13. Progress toward acoustic emission characterization for continuous monitoring of reactor pressure vessels

    International Nuclear Information System (INIS)

    Hutton, P.H.; Schwenk, E.B.; Kurtz, R.J.

    1980-01-01

    The purpose of this work is to evaluate the feasibility of detecting and analyzing flaw growth in an operating reactor vessel using acoustic emission (AE) data. A preliminary AE-flaw growth relationship has been developed encompassing six variables. This model relates AE count and energy to fatigue crack driving force ΔK. Pattern recognition has been examined as a means of distinguishing crack growth AE from other acoustic signals with encouraging results. The program is moving into hardware implementation of relationships for testing and refinement by monitoring tests in heavy section specimens and subscale structures. The hardware system will become a reactor monitor prototype. (orig.) [de

  14. NRC TLD Direct Radiation Monitoring Network. Volume 5, No. 2. Progress report, April-June 1985

    International Nuclear Information System (INIS)

    Jang, J.; Kramaric, M.; Cohen, L.

    1985-09-01

    The US Nuclear Regulatory Commission (NRC) Direct Radiation Monitoring Network provides continuous measurement of the ambient radiation levels around licensed NRC facilities, primarily power reactors. The Network is intended to measure radiation levels during routine facility operations and to establish background radiation levels used to assess the radiological impact of an unusual condition, such as an accident. This report presents the radiation levels measured around all facilities in the Network for the second quarter of 1985. A complete listing of the site facilities monitored is included

  15. Blind test results - measure of incessant progress in personnel monitoring services at Kudankulam Nuclear Power Project

    International Nuclear Information System (INIS)

    Jashi, K.B.; Ashok Kumar, A.; Pandaram, P.

    2018-01-01

    Personnel Monitoring Services (PMS) at Thermoluminescent Dosimeter (TLD) laboratory, Kudankulam Nuclear Power Project (KKNPP) involve monitoring of about 1500 radiation workers of KKNPP for external radiation exposure on monthly basis. Quality assurance in PMS provides an overall estimate of accuracy which depends not only upon the dosimeter quality and reader performance but also on data interpretation, applicable software and the system. Therefore it measures the effectiveness of quality control mechanism. Blind test is an effective tool to check the performance of the processor without their knowledge during routine processing of the service cards

  16. Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain.

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Friederike; Hanley, Patrick W; Scott, Dana P; Günther, Stephan; Feldmann, Heinz

    2015-10-01

    In late 2013, the largest documented outbreak of Ebola hemorrhagic fever started in Guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. In March 2014, Ebola virus (EBOV) was identified as the causative agent. This study compares the pathogenesis of a new EBOV strain, Makona, which was isolated in Guinea in 2014 with the prototype strain from the 1976 EBOV outbreak in the former Zaire. Both strains cause lethal disease in cynomolgus macaques with similar pathologic changes and hallmark features of Ebola hemorrhagic fever. However, disease progression was delayed in EBOV-Makona-infected animals, suggesting decreased rather than increased virulence of this most recent EBOV strain.

  17. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  18. The Progress of Mitophagy and Related Pathogenic Mechanisms of the Neurodegenerative Diseases and Tumor

    Directory of Open Access Journals (Sweden)

    Ying Song

    2015-01-01

    Full Text Available Mitochondrion, an organelle with two layers of membrane, is extremely vital to eukaryotic cell. Its major functions are energy center and apoptosis censor inside cell. The intactness of mitochondrial membrane is important to maintain its structure and function. Mitophagy is one kind of autophagy. In recent years, studies of mitochondria have shown that mitophagy is regulated by various factors and is an important regulation mechanism for organisms to maintain their normal state. In addition, abnormal mitophagy is closely related to several neurodegenerative diseases and tumor. However, the related signal pathway and its regulation mechanism still remain unclear. As a result, summarizing the progress of mitophagy and its related pathogenic mechanism not only helps to reveal the complicated molecular mechanism, but also helps to find a new target to treat the related diseases.

  19. NRC TLD Direct Radiation Monitoring Network. Progress report, January-June 1981

    International Nuclear Information System (INIS)

    1982-04-01

    This report provides the status and results of the NRC Thermoluminescent Dosimeter (TLD) Direct Radiation Monitoring Network. It presents the radiation levels measured in the vicinity of 55 NRC-licensed facility sites throughout the country for the first half of 1981. The program objectives, scope, and methodology are given. The TLD system, dosimeter location, data processing scheme, and quality assurance program are outlined

  20. A Step-by-Step Guide to Tier 2 Behavioral Progress Monitoring

    Science.gov (United States)

    Bruhn, Allison L.; McDaniel, Sara C.; Rila, Ashley; Estrapala, Sara

    2018-01-01

    Students who are at risk for or show low-intensity behavioral problems may need targeted, Tier 2 interventions. Often, Tier 2 problem-solving teams are charged with monitoring student responsiveness to intervention. This process may be difficult for those who are not trained in data collection and analysis procedures. To aid practitioners in these…

  1. Monitoring Spongospora subterranea Development in Potato Roots Reveals Distinct Infection Patterns and Enables Efficient Assessment of Disease Control Methods.

    Directory of Open Access Journals (Sweden)

    Tamilarasan Thangavel

    Full Text Available Spongospora subterranea is responsible for significant potato root and tuber disease globally. Study of this obligate (non-culturable pathogen that infects below-ground plant parts is technically difficult. The capacity to measure the dynamics and patterns of root infections can greatly assist in determining the efficacy of control treatments on disease progression. This study used qPCR and histological analysis in time-course experiments to measure temporal patterns of pathogen multiplication and disease development in potato (and tomato roots and tubers. Effects of delayed initiation of infection and fungicidal seed tuber and soil treatments were assessed. This study found roots at all plant developmental ages were susceptible to infection but that delaying infection significantly reduced pathogen content and resultant disease at final harvest. The pathogen was first detected in roots 15-20 days after inoculation (DAI and the presence of zoosporangia noted 15-45 DAI. Following initial infection pathogen content in roots increased at a similar rate regardless of plant age at inoculation. All fungicide treatments (except soil-applied mancozeb which had a variable response suppressed pathogen multiplication and root and tuber disease. In contrast to delayed inoculation, the fungicide treatments slowed disease progress (rate rather than delaying onset of infection. Trials under suboptimal temperatures for disease expression provided valuable data on root infection rate, demonstrating the robustness of monitoring root infection. These results provide an early measure of the efficacy of control treatments and indicate two possible patterns of disease suppression by either delayed initiation of infection which then proceeds at a similar rate or diminished epidemic rate.

  2. Monitoring Spongospora subterranea Development in Potato Roots Reveals Distinct Infection Patterns and Enables Efficient Assessment of Disease Control Methods.

    Science.gov (United States)

    Thangavel, Tamilarasan; Tegg, Robert S; Wilson, Calum R

    2015-01-01

    Spongospora subterranea is responsible for significant potato root and tuber disease globally. Study of this obligate (non-culturable) pathogen that infects below-ground plant parts is technically difficult. The capacity to measure the dynamics and patterns of root infections can greatly assist in determining the efficacy of control treatments on disease progression. This study used qPCR and histological analysis in time-course experiments to measure temporal patterns of pathogen multiplication and disease development in potato (and tomato) roots and tubers. Effects of delayed initiation of infection and fungicidal seed tuber and soil treatments were assessed. This study found roots at all plant developmental ages were susceptible to infection but that delaying infection significantly reduced pathogen content and resultant disease at final harvest. The pathogen was first detected in roots 15-20 days after inoculation (DAI) and the presence of zoosporangia noted 15-45 DAI. Following initial infection pathogen content in roots increased at a similar rate regardless of plant age at inoculation. All fungicide treatments (except soil-applied mancozeb which had a variable response) suppressed pathogen multiplication and root and tuber disease. In contrast to delayed inoculation, the fungicide treatments slowed disease progress (rate) rather than delaying onset of infection. Trials under suboptimal temperatures for disease expression provided valuable data on root infection rate, demonstrating the robustness of monitoring root infection. These results provide an early measure of the efficacy of control treatments and indicate two possible patterns of disease suppression by either delayed initiation of infection which then proceeds at a similar rate or diminished epidemic rate.

  3. A framework for prospectively defining progression rules for internal pilot studies monitoring recruitment.

    Science.gov (United States)

    Hampson, Lisa V; Williamson, Paula R; Wilby, Martin J; Jaki, Thomas

    2017-01-01

    Just over half of publicly funded trials recruit their target sample size within the planned study duration. When recruitment targets are missed, the funder of a trial is faced with the decision of either committing further resources to the study or risk that a worthwhile treatment effect may be missed by an underpowered final analysis. To avoid this challenging situation, when there is insufficient prior evidence to support predicted recruitment rates, funders now require feasibility assessments to be performed in the early stages of trials. Progression criteria are usually specified and agreed with the funder ahead of time. To date, however, the progression rules used are typically ad hoc. In addition, rules routinely permit adaptations to recruitment strategies but do not stipulate criteria for evaluating their effectiveness. In this paper, we develop a framework for planning and designing internal pilot studies which permit a trial to be stopped early if recruitment is disappointing or to continue to full recruitment if enrolment during the feasibility phase is adequate. This framework enables a progression rule to be pre-specified and agreed upon prior to starting a trial. The novel two-stage designs stipulate that if neither of these situations arises, adaptations to recruitment should be made and subsequently evaluated to establish whether they have been successful. We derive optimal progression rules for internal pilot studies which minimise the expected trial overrun and maintain a high probability of completing the study when the recruitment rate is adequate. The advantages of this procedure are illustrated using a real trial example.

  4. Retinal pigment epithelial detachments and tears, and progressive retinal degeneration in light chain deposition disease.

    Science.gov (United States)

    Spielberg, Leigh H; Heckenlively, John R; Leys, Anita M

    2013-05-01

    Light-chain deposition disease (LCDD) is a rare condition characterised by deposition of monoclonal immunoglobulin light chains (LCs) in tissues, resulting in varying degrees of organ dysfunction. This study reports the characteristic clinical ocular findings seen in advanced LCDD upon development of ocular fundus changes. This is the first report to describe this entity in vivo in a series of patients. A case series of ocular fundus changes in three patients with kidney biopsy-proven LCDD. All patients underwent best corrected visual acuity (BCVA) exam, perimetry, colour fundus photography and fluorescein angiography; two patients underwent indocyanine green angiography, optical coherence tomography, ultrasound and electroretinography; and one patient underwent fundus autofluorescence. Three patients, 53-60 years old at initial presentation, were studied. All three presented with night blindness, poor dark adaptation, metamorphopsia and visual loss. Examination revealed serous and serohaemorrhagic detachments, multiple retinal pigment epithelial (RPE) tears, diffuse RPE degeneration and progressive fibrotic changes. Neither choroidal neovascularisation nor other vascular abnormalities were present. Final best corrected visual acuity (BCVA) ranged from 20/40 to 20/300. Progressive LC deposition in the fundus seems to damage RPE pump function with flow disturbance between choroid and retina. This pathogenesis can explain the evolution to RPE detachments and subsequent rips and progressive retinal malfunction.

  5. HIV-1 DNA predicts disease progression and post-treatment virological control

    Science.gov (United States)

    Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

    2014-01-01

    In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

  6. Current and future disease progression of the chronic HCV population in the United States.

    Science.gov (United States)

    Zalesak, Martin; Francis, Kevin; Gedeon, Alex; Gillis, John; Hvidsten, Kyle; Kidder, Phyllis; Li, Hong; Martyn, Derek; Orne, Leslie; Smith, Amanda; Kwong, Ann

    2013-01-01

    Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  7. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

    Science.gov (United States)

    Hacker, Mallory L; DeLong, Mahlon R; Turchan, Maxim; Heusinkveld, Lauren E; Ostrem, Jill L; Molinari, Anna L; Currie, Amanda D; Konrad, Peter E; Davis, Thomas L; Phibbs, Fenna T; Hedera, Peter; Cannard, Kevin R; Drye, Lea T; Sternberg, Alice L; Shade, David M; Tonascia, James; Charles, David

    2018-06-29

    To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor. © 2018 American Academy of Neurology.

  8. Features of alpha-synuclein that could explain the progression and irreversibility of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Scarlet eGallegos

    2015-03-01

    Full Text Available Alpha-synuclein is a presynaptic protein expressed throughout the central nervous system, and it is the main component of Lewy bodies, one of the histopathological features of Parkinson’s disease (PD which is a progressive and irreversible neurodegenerative disorder. The conformational flexibility of α-synuclein allows it to adopt different conformations, i.e. bound to membranes or form aggregates, the oligomers are believed to be the more toxic species. In this review, we will focus on two major features of α-synuclein, transmission and toxicity that could help to understand the pathological characteristics of PD. One important feature of α-synuclein is its ability to be transmitted from neuron to neuron using mechanisms such as endocytosis, plasma membrane penetration or through exosomes, thus propagating the Lewy body pathology to different brain regions thereby contributing to the progressiveness of PD. The second feature of α-synuclein is that it confers cytotoxicity to recipient cells, principally when it is in an oligomeric state. This form causes mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, proteasome impairment, disruption of plasma membrane and pore formation, and lead to apoptosis pathway activation and consequent cell death. The complexity of α-synuclein oligomerization and formation of toxic species could be a major factor for the irreversibility of PD and could also explain the lack of successful therapies to halt the disease.

  9. Serum bilirubin: a simple routine surrogate marker of the progression of chronic kidney disease.

    Science.gov (United States)

    Moolchandani, K; Priyadarssini, M; Rajappa, M; Parameswaran, S; Revathy, G

    2016-10-01

    Studies suggest that Chronic Kidney Disease (CKD) is a global burden health associated with significant comorbid conditions. Few biochemical parameters have gained significance in predicting the disease progression. The present work aimed to study the association of the simple biochemical parameter of serum bilirubin level with the estimated glomerular filtration rate (eGFR), and to assess their association with the co-morbid conditions in CKD. We recruited 188 patients with CKD who attended a Nephrology out-patient department. eGFR values were calculated based on the serum creatinine levels using CKD-EPI formula. Various biochemical parameters including glucose, creatinine, uric acid, total and direct bilirubin were assayed in all study subjects. Study subjects were categorized into subgroups based on their eGFR values and their diabetic status and the parameters were compared among the different subgroups. We observed a significantly decreased serum bilirubin levels (p bilirubin levels (r = 0.92). We also observed a significant positive correlation between the eGFR levels and the direct bilirubin levels (r = 0.76). On multivariate linear regression analysis, we found that total and direct bilirubin independently predict eGFR, after adjusting for potential confounders (p bilirubin may help in predicting the early progression of CKD and more so in diabetic CKD.

  10. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

    Directory of Open Access Journals (Sweden)

    Sara Marcó

    2016-09-01

    Full Text Available Mucopolysaccharidosis type IIIC (MPSIIIC is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches.

  11. Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease.

    Science.gov (United States)

    Zager, Richard A; Johnson, Ali C; Becker, Kirsten

    2013-06-01

    Recent experimental work suggests a paradox: although uremia evokes systemic toxicities, in the setting of AKI, it can induce intrarenal cytoprotective and anti-inflammatory effects. Whether these influences can attenuate post-ischemic kidney disease progression remains unknown. To explore this possibility, male CD-1 mice were subjected to a 30-min unilateral (left) kidney ischemia model, previously shown to reduce renal mass by ∼50% over 2-3 weeks. Stepwise azotemia/acute uremia was superimposed by inducing different lengths of contralateral (right) kidney ischemia (0, 15, 18, 20 min). Subsequent loss of left renal mass (kidney weight) was assessed 2 weeks later and contrasted with the degree of initial azotemia 24-h BUN. A striking correlation between 24-h BUNs and 2-week left renal mass was observed (r, 0.77; P < 0.001). With 20 min of right kidney ischemia, left kidney size was completely preserved. This preservation did not result from increased tubular cell proliferation or decreased microvascular loss, as gauged by KI-67 and CD-34 immunohistochemistry, respectively. Rather, an early reduction in proximal tubule cell dropout (as judged by renal cortical N-acetyl-glucosaminidase content), with a subsequent preservation of tubule mass, was observed. In summary, these findings advance a novel concept: acute uremia can confer early post-ischemic cytoprotection resulting in a slowed progression of post-ischemic kidney disease.

  12. [Musical long-term memory throughout the progression of Alzheimer disease].

    Science.gov (United States)

    Groussard, Mathilde; Mauger, Caroline; Platel, Hervé

    2013-03-01

    In Alzheimer patients with a solid musical background, isolated case-reports have reported the maintenance of remarkable musical abilities despite clear difficulties in their verbal memory and linguistic functions. These reports have encouraged a number of scientists to undertake more systematic studies which would allow a rigorous approach to the analysis of musical memory in Alzheimer patients with no formal musical background. Although restricted in number, the latest data are controversial regarding preserved musical capacities in Alzheimer patients. Our current review of the literature addresses this topic and advances the hypothesis that the processes of musical memory are function of illness progression. In the earlier stages, the majority of evaluations concerned musical episodic memory and suggested a dysfunction of this memory whereas in the moderate and severe stages, musical semantic memory and implicit learning are the majority of investigations and seemed more resistant to Alzheimer disease. In summary, our current review bring to understand the memory circuits involved and highlight the necessity to adapted the investigational tools employed to conform with the severity of the signs and symptoms of progressive Alzheimer disease in order to demonstrate the preserved musical capacities.

  13. Blood Transcriptional Signatures for Disease Progression in a Rat Model of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Michał Korostyński

    2017-01-01

    Full Text Available Biomarkers of osteoarthritis (OA that can accurately diagnose the disease at the earliest stage would significantly support efforts to develop treatments for prevention and early intervention. We have sought to determine the time course of alterations in peripheral blood gene expression profile associated with the development of OA. Blood samples were collected from a tail vein of individual rats with monosodium iodoacetate- (MIA- induced OA (2, 14, 21, and 28 days after the treatment. We used whole-genome microarrays to reveal OA-related transcriptional alterations of 72 transcripts. Three main groups of coexpressed genes revealed diverse time-dependent profiles of up- and downregulation. Functional links that connect expression of the gradually downregulated genes to the G13 signaling pathway were indicated. The mRNA abundance levels of the identified transcripts were further analyzed in publicly available gene expression dataset obtained from a GARP study cohort of OA patients. We revealed three-gene signature differentially expressed in both rat and human blood (TNK2, KCTD2, and WDR37. The alterations in expression of the selected transcripts in peripheral blood samples of the patients indicate heterogeneity of the OA profiles potentially related to disease progress and severity of clinical symptoms. Our study identifies several potential stage-specific biomarkers of OA progression.

  14. Volcano Monitoring in Ecuador: Three Decades of Continuous Progress of the Instituto Geofisico - Escuela Politecnica Nacional

    Science.gov (United States)

    Ruiz, M. C.; Yepes, H. A.; Hall, M. L.; Mothes, P. A.; Ramon, P.; Hidalgo, S.; Andrade, D.; Vallejo Vargas, S.; Steele, A. L.; Anzieta, J. C.; Ortiz, H. D.; Palacios, P.; Alvarado, A. P.; Enriquez, W.; Vasconez, F.; Vaca, M.; Arrais, S.; Viracucha, G.; Bernard, B.

    2014-12-01

    In 1988, the Instituto Geofisico (IG) began a permanent surveillance of Ecuadorian volcanoes, and due to activity on Guagua Pichincha, SP seismic stations and EDM control lines were then installed. Later, with the UNDRO and OAS projects, telemetered seismic monitoring was expanded to Tungurahua, Cotopaxi, Cuicocha, Chimborazo, Antisana, Cayambe, Cerro Negro, and Quilotoa volcanoes. In 1992 an agreement with the Instituto Ecuatoriano de Electrificacion strengthened the monitoring of Tungurahua and Cotopaxi volcanoes with real-time SP seismic networks and EDM lines. Thus, background activity levels became established, which was helpful because of the onset of the 1999 eruptive activity at Tungurahua and Guagua Pichincha. These eruptions had a notable impact on Baños and Quito. Unrest at Cotopaxi volcano was detected in 2001-2002, but waned. In 2002 Reventador began its eruptive period which continues to the present and is closely monitored by the IG. In 2006 permanent seismic BB stations and infrasound sensors were installed at Tungurahua and Cotopaxi under a cooperative program supported by JICA, which allowed us to follow Tungurahua's climatic eruptions of 2006 and subsequent eruptions up to the present. Programs supported by the Ecuadorian Secretaria Nacional de Ciencia y Tecnologia and the Secretaria Nacional de Planificacion resulted in further expansion of the IG's monitoring infrastructure. Thermal and video imagery, SO2 emission monitoring, geochemical analyses, continuous GPS and tiltmeters, and micro-barometric surveillance have been incorporated. Sangay, Soche, Ninahuilca, Pululahua, and Fernandina, Cerro Azul, Sierra Negra, and Alcedo in the Galapagos Islands are now monitored in real-time. During this time, international cooperation with universities (Blaise Pascal & Nice-France, U. North Carolina, New Mexico Tech, Uppsala-Sweden, Nagoya, etc.), and research centers (USGS & UNAVCO-USA, IRD-France, NIED-Japan, SGC-Colombia, VAAC, MIROVA) has introduced

  15. Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

    Science.gov (United States)

    Geng, Xiao-Dong; Zheng, Wei; Wu, Cong-Mei; Wang, Shu-Qiang; Hong, Quan; Cai, Guang-Yan; Chen, Xiang-Mei; Wu, Di

    2016-01-01

    Background: Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD. Methods: Adult male Sprague–Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining. Results: In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs. Conclusions: In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury. PMID:26879011

  16. Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Davide Bolignano

    Full Text Available Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD. We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression.Systematic review and meta-analysis.Adults with DKD (either secondary to type 1 or 2 diabetes mellitus.Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs or quasi-RCTs without language or follow-up restriction.Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone alone or in combination.Primary outcome was progression to end-stage kidney disease (ESKD. Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16 but had apparently no tangible effects on renal function (GFR (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01. Evidence of benefits on the other outcomes of interest was inconclusive or lacking.Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD. High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.

  17. Disease progression in usual interstitial pneumonia compared with desquamative interstitial pneumonia. Assessment with serial CT

    International Nuclear Information System (INIS)

    Hartman, T.E.; Primack, S.L.; Kang, E.Y.

    1997-01-01

    Objective. To determine the outcome of areas of ground-glass attenuation and assess disease progression on serial high-resolution CT (HRCT) scans of patients with biopsy specimen-proved usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP). Materials and methods. Twelve patients with biopsy specimen-proved UIP and 11 patients with biopsy specimen-proved DIP who had initial and follow-up HRCT scans (median interval, 10 months) were reviewed. Eleven patients with UIP and 11 with DIP received treatment between the initial and follow-up CT scans. The scans were evaluated for the presence and extent of ground-glass attenuation, irregular linear opacities and honeycombing, and overall extent of parenchymal involvement. Results. On initial CT scans, all 12 patients with UIP had areas of ground-glass attenuation (mean±SD extent, 30±16%) and irregular lines (mean±SD extent, 17±7%) and 10 patients had honeycombing (mean±SD extent, 10±6%). All 11 patients with DIP had areas of ground-glass attenuation on initial HRCT scans (mean±SD extent, 51±26%), 5 patients had irregular linear opacities (mean±SD extent, 5±5%), and 1 patient had honeycombing. Nine of the 12 patients with UIP showed increase in the extent of ground-glass attenuation (n=6) or progression to irregular lines (n=2) or honeycombing (n=4) on follow-up as compared with only 2 patients with DIP who showed progression to irregular lines (n=1) or honeycombing (n=1) (p 2 test). Conclusion. In patients with UIP, areas of ground-glass attenuation usually increase in extent or progress to fibrosis despite treatment. Areas of ground-glass attenuation in most patients with DIP remain stable or improve with treatment. (authors)

  18. Longitudinal study of spatially heterogeneous emphysema progression in current smokers with chronic obstructive pulmonary disease.

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    Naoya Tanabe

    Full Text Available BACKGROUND: Cigarette smoke is the main risk factor for emphysema, which is a key pathology in chronic obstructive pulmonary disease (COPD. Low attenuation areas (LAA in computed tomography (CT images reflect emphysema, and the cumulative size distribution of LAA clusters follows a power law characterized by the exponent D. This property of LAA clusters can be explained by model simulation, where mechanical force breaks alveolar walls causing local heterogeneous lung tissue destruction. However, a longitudinal CT study has not investigated whether continuous smoking causes the spatially heterogeneous progression of emphysema. METHODS: We measured annual changes in ratios of LAA (LAA%, D and numbers of LAA clusters (LAN in CT images acquired at intervals of ≥ 3 years from 22 current and 31 former smokers with COPD to assess emphysema progression. We constructed model simulations using CT images to morphologically interpret changes in current smokers. RESULTS: D was decreased in current and former smokers, whereas LAA% and LAN were increased only in current smokers. The annual changes in LAA%, D, and LAN were greater in current, than in former smokers (1.03 vs. 0.37%, p=0.008; -0.045 vs. -0.01, p=0.004; 13.9 vs. 1.1, p=0.007, respectively. When LAA% increased in model simulations, the coalescence of neighboring LAA clusters decreased D, but the combination of changes in D and LAN in current smokers could not be explained by the homogeneous emphysema progression model despite cluster coalescence. Conversely, a model in which LAAs heterogeneously increased and LAA clusters merged somewhat in relatively advanced emphysematous regions could reflect actual changes. CONCLUSIONS: Susceptibility to parenchymal destruction induced by continuous smoking is not uniform over the lung, but might be higher in local regions of relatively advanced emphysema. These could result in the spatially heterogeneous progression of emphysema in current smokers.

  19. The fundamental role of mechanical properties in the progression of cancer disease and inflammation

    International Nuclear Information System (INIS)

    Mierke, Claudia Tanja

    2014-01-01

    The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in

  20. Anthesis, the infectious process and disease progress curves for fusarium head blight in wheat

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    Erlei Melo Reis

    2016-06-01

    Full Text Available ABSTRACT Fusarium head blight of wheat (Triticum aestivum, caused by the fungus Gibberella zeae, is a floral infecting disease that causes quantitative and qualitative losses to winter cereals. In Brazil, the sanitary situation of wheat has led to research in order to develop strategies for sustainable production, even under adverse weather conditions. To increase the knowledge of the relationship among the presence of anthesis, the infectious process, the disease progress and the saprophytic fungi present in wheat anthers, studies were conducted in the experimental field of University of Passo Fundo (UPF, using the cultivar Marfim, in the 2011 growing season. The disease incidence in spikes and spikelets was evaluated. The presence of exserted anthers increased the spike exposure time to the inoculum. The final incidence of fusarium head blight, in the field, was dependent on the presence of exserted anthers. The disease followed an aggregation pattern and its evolution increased with time, apparently showing growth according to secondary cycles. The fungi isolated from exserted anthers (Alternaria sp., Fusarium sp., Drechslera spp. and Epicoccum sp. did not compete for the infection site of fusarium head blight in wheat, not interfering with the incidence of F. graminearum.

  1. Host genetic risk factors for West Nile virus infection and disease progression.

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    Abigail W Bigham

    Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

  2. How accurate are interpretations of curriculum-based measurement progress monitoring data? Visual analysis versus decision rules.

    Science.gov (United States)

    Van Norman, Ethan R; Christ, Theodore J

    2016-10-01

    Curriculum based measurement of oral reading (CBM-R) is used to monitor the effects of academic interventions for individual students. Decisions to continue, modify, or terminate these interventions are made by interpreting time series CBM-R data. Such interpretation is founded upon visual analysis or the application of decision rules. The purpose of this study was to compare the accuracy of visual analysis and decision rules. Visual analysts interpreted 108 CBM-R progress monitoring graphs one of three ways: (a) without graphic aids, (b) with a goal line, or (c) with a goal line and a trend line. Graphs differed along three dimensions, including trend magnitude, variability of observations, and duration of data collection. Automated trend line and data point decision rules were also applied to each graph. Inferential analyses permitted the estimation of the probability of a correct decision (i.e., the student is improving - continue the intervention, or the student is not improving - discontinue the intervention) for each evaluation method as a function of trend magnitude, variability of observations, and duration of data collection. All evaluation methods performed better when students made adequate progress. Visual analysis and decision rules performed similarly when observations were less variable. Results suggest that educators should collect data for more than six weeks, take steps to control measurement error, and visually analyze graphs when data are variable. Implications for practice and research are discussed. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  3. Research progress of laser welding process dynamic monitoring technology based on plasma characteristics signal

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    Teng WANG

    2017-02-01

    Full Text Available During the high-power laser welding process, plasmas are induced by the evaporation of metal under laser radiation, which can affect the coupling of laser energy and the workpiece, and ultimately impact on the reliability of laser welding quality and process directly. The research of laser-induced plasma is a focus in high-power deep penetration welding field, which provides a promising research area for realizing the automation of welding process quality inspection. In recent years, the research of laser welding process dynamic monitoring technology based on plasma characteristics is mainly in two aspects, namely the research of plasma signal detection and the research of laser welding process modeling. The laser-induced plasma in the laser welding is introduced, and the related research of laser welding process dynamic monitoring technology based on plasma characteristics at home and abroad is analyzed. The current problems in the field are summarized, and the future development trend is put forward.

  4. The Umatilla Basin Natural Production Monitoring and Evaluation Project, 2008 Annual Progress Report.

    Energy Technology Data Exchange (ETDEWEB)

    Contor, Craig R.; Harris, Robin; King, Marty [Confederated Tribes of the Umatilla Indian Reservation

    2009-06-10

    The Umatilla Basin Natural Production Monitoring and Evaluation Project (UBNPMEP) is funded by Bonneville Power Administration (BPA) as directed by section 4(h) of the Pacific Northwest Electric Power Planning and Conservation Act of 1980 (P.L.96-501). This project is in accordance with and pursuant to measures 4.2A, 4.3C.1, 7.1A.2, 7.1C.3, 7.1C.4 and 7.1D.2 of the Northwest Power Planning Council's (NPPC) Columbia River Basin Fish and Wildlife Program (NPPC 1994). Work was conducted by the Fisheries Program of the Confederated Tribes of the Umatilla Indian Reservation (CTUIR). The UBNPMEP is coordinated with two Oregon Department of Fish and Wildlife (ODFW) research projects that also monitor and evaluate the success of the Umatilla Fisheries Restoration Plan. This project deals with the natural production component of the plan, and the ODFW projects evaluate hatchery operations (project No. 1990-005-00, Umatilla Hatchery M & E) and smolt outmigration (project No. 1989-024-01, Evaluation of Juvenile Salmonid Outmigration and Survival in the Lower Umatilla River). Collectively these three projects monitor and evaluate natural and hatchery salmonid production in the Umatilla River Basin. The need for natural production monitoring has been identified in multiple planning documents including Wy-Kan-Ush-Mi Wa-Kish-Wit Volume I, 5b-13 (CRITFC 1996), the Umatilla Hatchery Master Plan (CTUIR & ODFW 1990), the Umatilla Basin Annual Operation Plan, the Umatilla Subbasin Summary (CTUIR & ODFW 2001), the Subbasin Plan (CTUIR & ODFW 2004), and the Comprehensive Research, Monitoring, and Evaluation Plan (CTUIR and ODFW 2006). Natural production monitoring and evaluation is also consistent with Section III, Basinwide Provisions, Strategy 9 of the 2000 Columbia River Basin Fish and Wildlife Program (NPPC 1994, NPCC 2004). The Umatilla Basin M&E plan developed along with efforts to restore natural populations of spring and fall Chinook salmon, (Oncorhynchus tshawytsha), coho

  5. Yucca Mountain Biological Resources Monitoring Program. Progress report, January 1994--December 1994

    International Nuclear Information System (INIS)

    1995-07-01

    The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize the suitability of Yucca Mountain as a potential geological repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a potential repository. To ensure that site characterization activities do not adversely affect the environment at Yucca Mountain, a program has been implemented to monitor and mitigate potential impacts and ensure activities comply with applicable environmental regulations. This report describes the activities and accomplishments of EG and G Energy Measurements, Inc. (EG and G/EM) from January 1994 through December 1994 for six program areas within the Terrestrial Ecosystem component of the environmental program for the Yucca Mountain Site Characterization Project (YMP): Site Characterization Effects, Desert Tortoises (Gopherus agassizii), Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support

  6. Different decision deficits impair response inhibition in progressive supranuclear palsy and Parkinson’s disease

    Science.gov (United States)

    Rittman, Timothy; Nombela, Cristina; Fois, Alessandro; Coyle-Gilchrist, Ian; Barker, Roger A.; Hughes, Laura E.; Rowe, James B.

    2016-01-01

    Abstract Progressive supranuclear palsy and Parkinson’s disease have distinct underlying neuropathology, but both diseases affect cognitive function in addition to causing a movement disorder. They impair response inhibition and may lead to impulsivity, which can occur even in the presence of profound akinesia and rigidity. The current study examined the mechanisms of cognitive impairments underlying disinhibition, using horizontal saccadic latencies that obviate the impact of limb slowness on executing response decisions. Nineteen patients with clinically diagnosed progressive supranuclear palsy (Richardson’s syndrome), 24 patients with clinically diagnosed Parkinson’s disease and 26 healthy control subjects completed a saccadic Go/No-Go task with a head-mounted infrared saccadometer. Participants were cued on each trial to make a pro-saccade to a horizontal target or withhold their responses. Both patient groups had impaired behavioural performance, with more commission errors than controls. Mean saccadic latencies were similar between all three groups. We analysed behavioural responses as a binary decision between Go and No-Go choices. By using Bayesian parameter estimation, we fitted a hierarchical drift–diffusion model to individual participants’ single trial data. The model decomposes saccadic latencies into parameters for the decision process: decision boundary, drift rate of accumulation, decision bias, and non-decision time. In a leave-one-out three-way classification analysis, the model parameters provided better discrimination between patients and controls than raw behavioural measures. Furthermore, the model revealed disease-specific deficits in the Go/No-Go decision process. Both patient groups had slower drift rate of accumulation, and shorter non-decision time than controls. But patients with progressive supranuclear palsy were strongly biased towards a pro-saccade decision boundary compared to Parkinson’s patients and controls. This

  7. Different decision deficits impair response inhibition in progressive supranuclear palsy and Parkinson's disease.

    Science.gov (United States)

    Zhang, Jiaxiang; Rittman, Timothy; Nombela, Cristina; Fois, Alessandro; Coyle-Gilchrist, Ian; Barker, Roger A; Hughes, Laura E; Rowe, James B

    2016-01-01

    Progressive supranuclear palsy and Parkinson's disease have distinct underlying neuropathology, but both diseases affect cognitive function in addition to causing a movement disorder. They impair response inhibition and may lead to impulsivity, which can occur even in the presence of profound akinesia and rigidity. The current study examined the mechanisms of cognitive impairments underlying disinhibition, using horizontal saccadic latencies that obviate the impact of limb slowness on executing response decisions. Nineteen patients with clinically diagnosed progressive supranuclear palsy (Richardson's syndrome), 24 patients with clinically diagnosed Parkinson's disease and 26 healthy control subjects completed a saccadic Go/No-Go task with a head-mounted infrared saccadometer. Participants were cued on each trial to make a pro-saccade to a horizontal target or withhold their responses. Both patient groups had impaired behavioural performance, with more commission errors than controls. Mean saccadic latencies were similar between all three groups. We analysed behavioural responses as a binary decision between Go and No-Go choices. By using Bayesian parameter estimation, we fitted a hierarchical drift-diffusion model to individual participants' single trial data. The model decomposes saccadic latencies into parameters for the decision process: decision boundary, drift rate of accumulation, decision bias, and non-decision time. In a leave-one-out three-way classification analysis, the model parameters provided better discrimination between patients and controls than raw behavioural measures. Furthermore, the model revealed disease-specific deficits in the Go/No-Go decision process. Both patient groups had slower drift rate of accumulation, and shorter non-decision time than controls. But patients with progressive supranuclear palsy were strongly biased towards a pro-saccade decision boundary compared to Parkinson's patients and controls. This indicates a prepotency of

  8. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease.

    Science.gov (United States)

    Cifuentes, Diana; Poittevin, Marine; Dere, Ekrem; Broquères-You, Dong; Bonnin, Philippe; Benessiano, Joëlle; Pocard, Marc; Mariani, Jean; Kubis, Nathalie; Merkulova-Rainon, Tatyana; Lévy, Bernard I

    2015-01-01

    Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 3