WorldWideScience

Sample records for specific diseases including

  1. Disease specific protein corona

    Science.gov (United States)

    Rahman, M.; Mahmoudi, M.

    2015-03-01

    It is now well accepted that upon their entrance into the biological environments, the surface of nanomaterials would be covered by various biomacromolecules (e.g., proteins and lipids). The absorption of these biomolecules, so called `protein corona', onto the surface of (nano)biomaterials confers them a new `biological identity'. Although the formation of protein coronas on the surface of nanoparticles has been widely investigated, there are few reports on the effect of various diseases on the biological identity of nanoparticles. As the type of diseases may tremendously changes the composition of the protein source (e.g., human plasma/serum), one can expect that amount and composition of associated proteins in the corona composition may be varied, in disease type manner. Here, we show that corona coated silica and polystyrene nanoparticles (after interaction with in the plasma of the healthy individuals) could induce unfolding of fibrinogen, which promotes release of the inflammatory cytokines. However, no considerable releases of inflammatory cytokines were observed for corona coated graphene sheets. In contrast, the obtained corona coated silica and polystyrene nanoparticles from the hypofibrinogenemia patients could not induce inflammatory cytokine release where graphene sheets do. Therefore, one can expect that disease-specific protein coronas can provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances.

  2. Lung Disease Including Asthma and Adult Vaccination

    Science.gov (United States)

    ... can make it hard to breathe. Certain vaccinepreventable diseases can also increase swelling of your airways and lungs. The combination of the two can lead to pneumonia and other serious respiratory illnesses. Vaccines are one of the safest ways ...

  3. A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid, and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.

    Science.gov (United States)

    Chwist, Alina; Hartleb, Marek; Lekstan, Andrzej; Kukla, Michał; Gutkowski, Krzysztof; Kajor, Maciej

    2014-01-01

    Histopathological risk factors for end-stage liver failure in patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. There is a need for noninvasive diagnostic methods for these 2 conditions. The aim of this study was to investigate new laboratory variables with a predictive potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. The study involved 70 patients with histologically proven NAFLD of varied severity. Additional laboratory variables included zonulin, haptoglobin, visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA), hyaluronic acid, and interleukin 6. Patients with NASH (NAFLD activity score of ≥5) had significantly higher HOMA-IR values and serum levels of visfatin, haptoglobin, and zonulin as compared with those without NASH on histological examination. Advanced fibrosis was found in 16 patients (22.9%) and the risk factors associated with its prevalence were age, the ratio of erythrocyte count to red blood cell distribution width, platelet count, and serum levels of visfatin and TPSA. Based on these variables, we constructed a scoring system that differentiated between NAFLD patients with and without advanced fibrosis with a sensitivity of 75% and specificity of 100% (area under the receiver operating characteristic curve, 0.93). The scoring system based on the above variables allows to predict advanced fibrosis with high sensitivity and specificity. However, its clinical utility should be verified in further studies involving a larger number of patients.

  4. Diseases of the abdomen including the pelvis

    International Nuclear Information System (INIS)

    Kido, C.; Tanaka, H.

    1983-01-01

    This book discusses the following diseases: fatty liver; cystic disease of the liver; liver abscess; liver cirrhosis; hepatic hemangioma; cholelithiasis; primary liver cancer; cholangioma; cancer of the common bile duct; pancreatic cyst; pancreatic calculi; chronic pancreatitis; pancreatic pseudocyst; chronic pancreatitis: pancreatic fatty degeneration; cancer of the pancreas; nonfunctioning kidney: chalk kidney; polycystic kidney; perirenal calcified abscess; renal infarct; cancer of the renal pelvis; adrenal pheochromocytoma; adenoma of the adrenal cortex; leiomyosarcoma of the stomach; malignant mesothelioma; intraperitoneal abscess; perityphlic abscess; retroperitoneal reticulum cell sarcoma; and retroperitoneal cyst

  5. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    Science.gov (United States)

    ... Submit Button NCHS Home Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema Recommend on Facebook ... Percent of visits to office-based physicians with COPD indicated on the medical record: 3.2% Source: ...

  6. Disease specific therapies in leukodystrophies and leukoencephalopathies

    NARCIS (Netherlands)

    Helman, Guy; van Haren, Keith; Bonkowsky, Joshua L.; Bernard, Genevieve; Pizzino, Amy; Braverman, Nancy; Suhr, Dean; Patterson, Marc C.; Ali Fatemi, S.; Leonard, Jeff; van der Knaap, Marjo S.; Back, Stephen A.; Damiani, Stephen; Goldman, Steven A.; Takanohashi, Asako; Petryniak, Magdalena; Rowitch, David; Messing, Albee; Wrabetz, Lawrence; Schiffmann, Raphael; Eichler, Florian; Escolar, Maria L.; Vanderver, Adeline

    2015-01-01

    Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have historically had no etiologic or disease specific therapeutic approaches. Recently, a greater understanding of the pathologic mechanisms

  7. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

    Science.gov (United States)

    Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

    2015-01-01

    The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

  8. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  9. Prevention of metabolic diseases: fruits (including fruit sugars) vs. vegetables.

    Science.gov (United States)

    Kuzma, Jessica N; Schmidt, Kelsey A; Kratz, Mario

    2017-07-01

    To discuss recent evidence from observational and intervention studies on the relationship between fruit and vegetable (F&V) consumption and metabolic disease. Observational studies have consistently demonstrated a modest inverse association between the intake of fruit and leafy green vegetables, but not total vegetables, and biomarkers of metabolic disease as well as incident type 2 diabetes mellitus. This is in contrast to limited evidence from recently published randomized controlled dietary intervention trials, which - in sum - suggests little to no impact of increased F&V consumption on biomarkers of metabolic disease. Evidence from observational studies that fruit and leafy green vegetable intake is associated with lower type 2 diabetes risk and better metabolic health could not be confirmed by dietary intervention trials. It is unclear whether this discrepancy is because of limitations inherent in observational studies (e.g., subjective dietary assessment methods, residual confounding) or due to limitations in the few available intervention studies (e.g., short duration of follow-up, interventions combining whole fruit and fruit juice, or lack of compliance). Future studies that attempt to address these limitations are needed to provide more conclusive insight into the impact of F&V consumption on metabolic health.

  10. 7 CFR 1755.98 - List of telecommunications specifications included in other 7 CFR parts.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false List of telecommunications specifications included in... (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE TELECOMMUNICATIONS POLICIES ON SPECIFICATIONS, ACCEPTABLE MATERIALS, AND STANDARD CONTRACT FORMS § 1755.98 List of telecommunications specifications...

  11. The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

    Science.gov (United States)

    Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

    2018-02-01

    Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Disease-Specific Care: Spine Surgery Program Development.

    Science.gov (United States)

    Koerner, Katie; Franker, Lauren; Douglas, Barbara; Medero, Edgardo; Bromeland, Jennifer

    2017-10-01

    Minimal literature exists describing the process for development of a Joint Commission comprehensive spine surgery program within a community hospital health system. Components of a comprehensive program include structured communication across care settings, preoperative education, quality outcomes tracking, and patient follow-up. Organizations obtaining disease-specific certification must have clear knowledge of the planning, time, and overall commitment, essential to developing a successful program. Health systems benefit from disease-specific certification because of their commitment to a higher standard of service. Certification standards establish a framework for organizational structure and management and provide institutions a competitive edge in the marketplace. A framework for the development of a spine surgery program is described to help guide organizations seeking disease-specific certification. In developing a comprehensive program, it is critical to define the program's mission and vision, identify key stakeholders, implement clinical practice guidelines, and evaluate program outcomes.

  13. Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

    Science.gov (United States)

    Jang, Jiho; Yoo, Jeong-Eun; Lee, Jeong-Ah; Lee, Dongjin R; Kim, Ji Young; Huh, Yong Jun; Kim, Dae-Sung; Park, Chul-Yong; Hwang, Dong-Youn; Kim, Han-Soo; Kang, Hoon-Chul; Kim, Dong-Wook

    2012-03-31

    The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

  14. Variation of a test's sensitivity and specificity with disease prevalence.

    Science.gov (United States)

    Leeflang, Mariska M G; Rutjes, Anne W S; Reitsma, Johannes B; Hooft, Lotty; Bossuyt, Patrick M M

    2013-08-06

    Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p disease prevalence; there was no such systematic effect for sensitivity. The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

  15. Description of an oral Chagas disease outbreak in Venezuela, including a vertically transmitted case.

    Science.gov (United States)

    Noya, Belkisyolé Alarcón de; Pérez-Chacón, Gladymar; Díaz-Bello, Zoraida; Dickson, Sonia; Muñoz-Calderón, Arturo; Hernández, Carlos; Pérez, Yadira; Mauriello, Luciano; Moronta, Eyleen

    2017-08-01

    We describe the eleventh major outbreak of foodborne Trypanosoma cruzi transmission in urban Venezuela, including evidence for vertical transmission from the index case to her fetus. After confirming fetal death at 24 weeks of gestation, pregnancy interruption was performed. On direct examination of the amniotic fluid, trypomastigotes were detected. T. cruzi specific-polymerase chain reaction (PCR) also proved positive when examining autopsied fetal organs. Finally, microscopic fetal heart examination revealed amastigote nests. Acute orally transmitted Chagas disease can be life threatening or even fatal for pregnant women and unborn fetuses owing to vertical transmission. There is therefore an urgent need to improve national epidemiologic control measures.

  16. Specific Profile of Tau Isoforms in Argyrophylic Grain Disease

    Directory of Open Access Journals (Sweden)

    Alberto Rábano

    2013-01-01

    Full Text Available Argyrophylic grain disease (AGD is a neurodegenerative condition that has been classified among the sporadic tauopathies. Entities in this group present intracellular aggregates of hyperphosphorylated tau, giving rise to characteristic neuronal and glial inclusions. In different tauopathies, the proportion of several tau isoforms present in the aggregates shows specific patterns. AGD has been tentatively classified in the 4R group (predominance of 4R tau isoforms together with progressive supranuclear palsy and corticobasal degeneration. Pick's disease is included in the 3R group (predominance of 3R isoforms, whereas tau pathology of Alzheimer's disease represents and intermediate group (3 or 4 repeats [3R plus 4R, respectively] isoforms. In this work, we have analyzed tau present in aggregates isolated from brain samples of patients with argyrophylic grain disease. Our results indicate that the main tau isoform present in aggregates obtained from patients with AGD is a hyperphosphorylated isoform containing exons 2 and 10 but lacking exon 3.

  17. Numerical Treatment of Two-phase Flow in Porous Media Including Specific Interfacial Area

    KAUST Repository

    El-Amin, Mohamed

    2015-06-01

    In this work, we present a numerical treatment for the model of two-phase flow in porous media including specific interfacial area. For numerical discretization we use the cell-centered finite difference (CCFD) method based on the shifting-matrices method which can reduce the time-consuming operations. A new iterative implicit algorithm has been developed to solve the problem under consideration. All advection and advection-like terms that appear in saturation equation and interfacial area equation are treated using upwind schemes. Selected simulation results such as pc–Sw–awn surface, capillary pressure, saturation and specific interfacial area with various values of model parameters have been introduced. The simulation results show a good agreement with those in the literature using either pore network modeling or Darcy scale modeling.

  18. Nailfold capillaroscopy: Specific features in Fabry disease.

    Science.gov (United States)

    Wasik, Jan S; Simon, Roger W; Meier, Thomas; Steinmann, Beat; Amann-Vesti, Beatrice R

    2009-01-01

    Fabry disease is a rare X-linked disorder caused by deficiency of alpha-galactosidase A. The metabolic defect results in the progressive accumulation of globotriaosylceramide within vascular cells leading to renal, cardiac and cerebrovascular manifestations. The aim of this study was to evaluate nailfold capillaroscopy as a non-invasive diagnostic tool in Fabry disease and to characterize morphological and functional changes of the capillaries in vivo. Twenty-five consecutive patients with Fabry disease (17 males) without enzyme-replacement therapy had been studied by fluorescence nailfold capillaroscopy. Macrocirculation of digital arteries was tested by digital pulse volume recording and patients had been asked about the presence of Raynaud phenomenon. Significant more bushy capillaries and clusters were present in Fabry patients (72%) compared to healthy controls (10%). No avascular fields had been seen, and in only one patient atypical architecture and in another one a giant capillary was present. Enhanced natrium-fluorescein diffusion into the pericapillary area has been observed in three male patients. Six patients (one female) reported Raynaud phenomenon of all fingers. In Fabry disease morphological and functional microangiopathy of nailfold capillaries is present. Furthermore, these new findings might explain, at least in part, the unusual high frequency of Raynaud phenomenon in Fabry patients, which has not been described so far. Our data suggest that capillaroscopy might be used as an additional non-invasive diagnostic tool for Fabry disease.

  19. Analysis of general and specific combining abilities of popcorn populations, including selfed parents

    Directory of Open Access Journals (Sweden)

    José Marcelo Soriano Viana

    2003-12-01

    Full Text Available Estimation of general and specific combining ability effects in a diallel analysis of cross-pollinating populations, including the selfed parents, is presented in this work. The restrictions considered satisfy the parametric values of the GCA and SCA effects. The method is extended to self-pollinating populations (suitable for other species, without the selfed parents. The analysis of changes in population means due to inbreeding (sensitivity to inbreeding also permits to assess the predominant direction of dominance deviations and the relative genetic variability in each parent population. The methodology was used to select popcorn populations for intra- and inter-population breeding programs and for hybrid production, developed at the Federal University of Viçosa, MG, Brazil. Two yellow pearl grain popcorn populations were selected.

  20. STRESS AS PREDISPOSING FACTOR OF SOME CHRONIC DISEASES INCLUDING PERIODONTAL DISEASE

    Directory of Open Access Journals (Sweden)

    Dewi-Nurul M Dewi-Nurul

    2006-04-01

    Full Text Available Stress is hypothesized as a common pathway for several related chronic diseases of man. Psychosocial stress as modified by perceptions and coping by patients can lead to physical processes. Psychoneuroimmunologic (PNI studies have suggested that psychosocial stress can alter immune function and increase vulnerability to illnesses. The patients also have high sensitivity to periodontal disease (PD. This article describes the association of stress as a physiological response to diseases such as PD, rheumatoid arthritis (RA, and inflammatory bowel disease. The psychosocial stress can lead to physiological processes through 1 the hypothalamic-pituitary-adrenal (HPA axis leading to glucocortico-steroid secretion; 2 the autonomic nervous system, resulting in the release of catecholamine; or 3 the hypothalamic-pituitary-gonadal axis, resulting in the release of sex hormones. These processes may affect chronic diseases. It can be concluded that psychosocial stress in periodontal disease patients must be considered and social support must be provided in order to achieve an optimum periodontal therapy result.

  1. Variation of a test's sensitivity and specificity with disease prevalence

    NARCIS (Netherlands)

    Leeflang, Mariska M. G.; Rutjes, Anne W. S.; Reitsma, Johannes B.; Hooft, Lotty; Bossuyt, Patrick M. M.

    2013-01-01

    Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23

  2. A model for firm-specific strategic wisdom : including illustrations and 49 guiding questions

    NARCIS (Netherlands)

    van Straten, Roeland Peter

    2017-01-01

    This PhD thesis provides an answer to the question ‘How may one think strategically’. It does so by presenting a new prescriptive ‘Model for Firm-Specific Strategic Wisdom’. This Model aims to guide any individual strategist in his or her thinking from a state of firm-specific ‘ignorance’ to a state

  3. Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited

    DEFF Research Database (Denmark)

    Martens, Pernille; Worm, Signe Westring; Lundgren, Bettina

    2004-01-01

    Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited.Martens P, Worm SW, Lundgren B, Konradsen HB, Benfield T. Department of Infectious Diseases 144, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. pernillemartens@yahoo.com BACKGROUND: Invasive infection...... with Streptococcus pneumoniae (pneumococci) causes significant morbidity and mortality. Case series and experimental data have shown that the capsular serotype is involved in the pathogenesis and a determinant of disease outcome. METHODS: Retrospective review of 464 cases of invasive disease among adults diagnosed...

  4. Borrelia burgdorferi-specific IgA in Lyme Disease

    Directory of Open Access Journals (Sweden)

    Christina D'Arco

    2017-05-01

    Full Text Available The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223-modVlsE(275-291, a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8% from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease.

  5. Borrelia burgdorferi-specific IgA in Lyme Disease.

    Science.gov (United States)

    D'Arco, Christina; Dattwyler, Raymond J; Arnaboldi, Paul M

    2017-05-01

    The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8%) from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Screening for Specific Language Impairment in Preschool Children: Evaluating a Screening Procedure Including the Token Test

    Science.gov (United States)

    Willinger, Ulrike; Schmoeger, Michaela; Deckert, Matthias; Eisenwort, Brigitte; Loader, Benjamin; Hofmair, Annemarie; Auff, Eduard

    2017-01-01

    Specific language impairment (SLI) comprises impairments in receptive and/or expressive language. Aim of this study was to evaluate a screening for SLI. 61 children with SLI (SLI-children, age-range 4-6 years) and 61 matched typically developing controls were tested for receptive language ability (Token Test-TT) and for intelligence (Wechsler…

  7. Reliability and limitation of various diagnostic methods including nuclear medicine in myocardial disease

    International Nuclear Information System (INIS)

    Tokuyasu, Yoshiki; Kusakabe, Kiyoko; Yamazaki, Toshio

    1981-01-01

    Electrocardiography (ECG), echocardiography, nuclear method, cardiac catheterization, left ventriculography and endomyocardial biopsy (biopsy) were performed in 40 cases of cardiomyopathy (CM), 9 of endocardial fibroelastosis and 19 of specific heart muscle disease, and the usefulness and limitation of each method was comparatively estimated. In CM, various methods including biopsy were performed. The 40 patients were classified into 3 groups, i.e., hypertrophic (17), dilated (20) and non-hypertrophic.non-dilated (3) on the basis of left ventricular ejection fraction and hypertrophy of the ventricular wall. The hypertrophic group was divided into 4 subgroups: 9 septal, 4 apical, 2 posterior and 2 anterior. The nuclear study is useful in assessing the site of the abnormal ventricular thickening, perfusion defect and ventricular function. Echocardiography is most useful in detecting asymmetric septal hypertrophy. The biopsy gives the sole diagnostic clue, especially in non-hypertrophic.non-dilated cardiomyopathy. ECG is useful in all cases but correlation with the site of disproportional hypertrophy was not obtained. (J.P.N.)

  8. Rise and fall of public opposition in specific social movements. [Including nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Leahy, P J [Akron Univ., OH (USA); Mazur, A [Syracuse Univ., NY (USA)

    1980-08-01

    This article reports a comparative study of four 'specific' social movements which involve aspects of technological controversy: Fluoridation, the ABM, Nuclear Power Plants, and Legalized Abortion. A theoretical model of the rise and fall of public opposition in these movements over time is suggested. Quantitative indicators are developed and applied to this historical model. Rise and fall of controversy follows a regular sequence: Activities of protest leaders increase during periods of great national concern over issues that are complementary to the movement; during these periods, social and economic resources are relatively available to the movement. As the activity of protest leaders increases, mass media coverage of their activities increases. As mass media coverage increases, opposition to the technology among the wider public increases. As the activity of the leaders wanes, mass media coverage declines, and so does opposition among the wider public. The paper concludes with a discussion of the relevance of this perspective for making predictions about the future course of 'specific' social movements.

  9. Enantiomer-specific ketorolac pharmacokinetics in young women, including pregnancy and postpartum period

    Directory of Open Access Journals (Sweden)

    Aida Kulo

    2017-02-01

    Full Text Available Racemic ketorolac clearance (CL is significantly higher at delivery, but S-ketorolac disposition determines the analgesic effects. The aim of this study was to investigate the effect of pregnancy and postpartum period on enantiomer-specific (S and R intravenous (IV ketorolac pharmacokinetics (PKs. Data in women shortly following cesarean delivery (n=39 were pooled with data in a subgroup of these women that was reevaluated in the later postpartum period (postpartum group, n=8/39 and with eight healthy female volunteers. All women received single IV bolus of 30 mg ketorolac tromethamine. Five plasma samples were collected at 1, 2, 4, 6, and 8 hours and plasma concentrations were determined using high performance liquid chromatography. Enantiomer-specific PKs were calculated using PKSolver. Unpaired analysis showed that distribution volume at steady state (Vss, L/kg for S- and R-ketorolac was significantly higher in women shortly following cesarean delivery (n=31 compared to postpartum group (n=8 or to healthy female volunteers (n=8. CL, CL to body weight, and CL to body surface area (CL/BSA for S- and R-ketorolac were also significantly higher in women following delivery. In addition, S/R-ketorolac CL/BSA ratio was significantly higher at delivery. Paired PK analysis in eight women shortly following delivery and in postpartum group showed the same pattern. Finally, the simultaneous increase in CL and Vss resulted in similar estimates for elimination half-life in both unpaired and paired analysis. In conclusion, pregnancy affects S-, R-, and S/R-ketorolac disposition. This is of clinical relevance since S-ketorolac (analgesia CL is even more increased compared to R-ketorolac CL, and S/R-ketorolac CL ratio is higher following delivery compared to postpartum period or to healthy female volunteers.

  10. Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Lynne V. McFarland

    2018-05-01

    Full Text Available BackgroundAs the use and diversity of probiotic products expands, the choice of an appropriate type of probiotic is challenging for both medical care professionals and the public alike. Two vital factors in choosing the appropriate probiotic are often ignored, namely, the probiotic strain-specificity and disease-specificity for efficacy. Reviews and meta-analyses often pool together different types of probiotics, resulting in misleading conclusions of efficacy.MethodsA systematic review of the literature (1970–2017 assessing strain-specific and disease-specific probiotic efficacy was conducted. Trials were included for probiotics with an identifiable strain (either single strain or mixtures of strains that had at least two randomized, controlled trials for each type of disease indication. The goal was to determine if probiotic strains have strain and/or disease-specific efficacy.ResultsWe included 228 trials and found evidence for both strain specificity and disease specificity for the efficacy of specific probiotic strains. Significant efficacy evidence was found for 7 (70% of probiotic strain(s among four preventive indications and 11 (65% probiotic strain(s among five treatment indications. Strain-specific efficacy for preventing adult antibiotic-associated diarrhea was clearly demonstrated within the Lactobacillus species [e.g., by the mixture of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+®, by L. casei DN114001 (Actimel® and by Lactobacillus reuteri 55730], while other Lactobacillus strains did not show efficacy. Significant disease-specific variations in efficacy was demonstrated by L. rhamnosus GG and Saccharomyces boulardii CNCM I-745, as well as other probiotic strains.ConclusionStrong evidence was found supporting the hypothesis that the efficacy of probiotics is both strain-specific and disease-specific. Clinical guidelines and meta-analyses need to recognize the

  11. Specificity of facelift surgery, including mid facelift, in case of facial palsy.

    Science.gov (United States)

    Le Louarn, C

    2015-10-01

    The asymmetry created by the facial palsy is of course a cause of demand for facelift surgery. As this lifting action is specific and different from the standard procedures, 3 zones of analysis are proposed: first the frontal and temporal areas with the direct eyebrow lift, second the neck and jawline with action on the depressor anguli oris for the non-paralyzed side and the anterior sub SMAS dissection and third the midface. A new and more simple technique of concentric malar lift is proposed. The first publication on concentric malar lift was made 11years ago. Midface rejuvenation stays very challenging. As a proof of that, many authors prefer a partial rejuvenation of mid face with fat reinjection, with no effect on skin excess, even if all the MRI studies demonstrated no fat loss with time but only fat transfer. This proves that midface lift did not acquire enough simplicity, reliability to become a standard procedure. Six hundred concentric malar lift later, a technical simplification validated with 110 patients and 2years of follow-up is proposed. The improvement is due to a new way to pass the threads deeply on the bone, using permanent barbed sutures. This surgery becomes easier and more efficient. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Screening for Specific Language Impairment in Preschool Children: Evaluating a Screening Procedure Including the Token Test.

    Science.gov (United States)

    Willinger, Ulrike; Schmoeger, Michaela; Deckert, Matthias; Eisenwort, Brigitte; Loader, Benjamin; Hofmair, Annemarie; Auff, Eduard

    2017-10-01

    Specific language impairment (SLI) comprises impairments in receptive and/or expressive language. Aim of this study was to evaluate a screening for SLI. 61 children with SLI (SLI-children, age-range 4-6 years) and 61 matched typically developing controls were tested for receptive language ability (Token Test-TT) and for intelligence (Wechsler Preschool-and-Primary-Scale-of-Intelligence-WPPSI). Group differences were analyzed using t tests, as well as direct and stepwise discriminant analyses. The predictive value of the WPPSI with respect to TT performance was analyzed using regression analyses. SLI-children performed significantly worse on both TT and WPPSI ([Formula: see text]). The TT alone yielded an overall classification rate of 79%, the TT and the WPPSI together yielded an overall classification rate of 80%. TT performance was significantly predicted by verbal intelligence in SLI-children and nonverbal intelligence in controls whilst WPPSI subtest arithmetic was predictive in both groups. Without further research, the Token Test cannot be seen as a valid and sufficient tool for the screening of SLI in preschool children but rather as a tool for the assessment of more general intellectual capacities. SLI-children at this age already show impairments typically associated with SLI which indicates the necessity of early developmental support or training. Token Test performance is possibly an indicator for a more general developmental factor rather than an exclusive indicator for language difficulties.

  13. Generic and disease-specific measures of quality of life in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Bhattacharya, Sumangala; Vogel, A.; Hansen, M.L.

    2010-01-01

    The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD).......The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD)....

  14. SPECIFICITY OF THE PRECIPITIN REACTION IN TOBACCO MOSAIC DISEASE.

    Science.gov (United States)

    Beale, H P

    1931-09-30

    1. Leaf extracts of Sudan grass, Hippeastrum equestre Herb., lily, and Abutilon striatum Dicks. (A. Thompsoni hort.), each affected with its respective mosaic disease, and peach affected with yellows disease, were tested for their ability to precipitate antiserum for virus extract of tobacco mosaic disease. No precipitate occurred. 2. Nicotiana glutinosa L., N. rustica L., and Martynia louisiana Mill. were added to the list of hosts of tobacco mosaic virus which have been tested with antiserum for the same virus in N. tabacum L. var. Turkish. The object was to determine the presence or absence of material reacting with the specific precipitins such as that already demonstrated in extracts of tomato, pepper, and petunia affected with the same virus. The presence of specific substances was demonstrated in every case. 3. The viruses of ringspot and cucumber mosaic diseases were multiplied in Turkish tobacco and leaf extracts of the affected plants were used in turn as antigens in precipitin tests with antiserum for tobacco mosaic virus extract of Turkish tobacco. A slight precipitation resulted in the tubes containing undiluted antiserum and virus extract such as occurs when juice from normal tobacco is used with undiluted antiserum. No precipitate was demonstrable that was specific for virus extracts of tobacco affected with either ringspot or cucumber mosaic disease. 4. The results favor the interpretation that the specific antigenic substance in virus extract of tobacco mosaic disease is foreign antigenic material, possibly virus itself, not altered host protein.

  15. A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis.

    Science.gov (United States)

    Lee, Kyung-Yil

    2017-06-01

    Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

  16. Allergen-specific immunotherapy and risk of autoimmune disease

    DEFF Research Database (Denmark)

    Linneberg, Allan; Madsen, Flemming; Skaaby, Tea

    2012-01-01

    After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic.......After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic....

  17. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): a clinicoradiological profile of three cases including two with skeletal disease

    International Nuclear Information System (INIS)

    Gupta, Priya; Babyn, Paul

    2008-01-01

    Originally described as sinus histiocytosis with massive lymphadenopathy, Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder with a distinctive microscopic appearance. A rare entity, RDD is often under-diagnosed because of a low index of suspicion by both radiologist and pathologist. Through this article, we wish to apprise radiologists of the spectrum of disease that can be encountered in this disorder. RDD can mimic other common childhood skeletal diseases including benign Langerhans cell histiocytosis and lymphoma. The clinical and radiological manifestations of RDD vary depending upon organ involvement, and its imaging features are often confused with those of other disorders. RDD should be considered in the differential diagnosis of unifocal and multifocal skeletal involvement caused by granulomatous diseases, infections, pseudogranulomatous lesions and malignancy. As long-term outcome is usually good, a conservative approach is justified in most cases. Contrasted with its typical appearance, presenting with bilateral symmetrical cervical adenopathy (as shown in one patient), we also report extranodal involvement of bone in two patients. Extranodal disease occurs along with concomitant nodal disease in about 43% of patients. In 23% of patients, isolated extranodal RDD can be seen, most commonly in the head and neck. In two of our patients, we observed extranodal involvement with skeletal involvement away from the head and neck not associated with lymphadenopathy. Skeletal involvement in RDD without lymphadenopathy is rare, occurring only in 2% of all the patients reported to date. (orig.)

  18. Determining T-cell specificity to understand and treat disease

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker; Newell, Evan W.

    2017-01-01

    Adaptive immune responses and immunopathogeneses are based on the ability of T cells to respond to specific antigens. Consequently, understanding T-cell recognition patterns in health and disease involves studying the complexity and genetic heterogeneity of the antigen recognition pathway, which...

  19. Disease-specific self-efficacy in spasmodic dysphonia patients.

    Science.gov (United States)

    Hu, Amanda; Isetti, Derek; Hillel, Allen D; Waugh, Patricia; Comstock, Bryan; Meyer, Tanya K

    2013-03-01

    Self-efficacy (SE) is an optimistic self-belief that one can perform a novel task. This concept involves empowerment, self-esteem, and adaptation to a stressful situation. SE is a strong predictor of health behaviors. Our objectives were to study SE in spasmodic dysphonia (SD) and to develop a disease-specific SE-SD scale. Prospective study. Academic hospital. Disease-specific SE-SD items were developed with laryngologists, speech pathologists, and SD patients. These items, General SE Scale, Voice Handicap Index-10 (VHI-10), Consensus Auditory Perceptual Evaluation of Voice (CAPE-V), and Hospital Anxiety and Depression Scale (HADS), were administered to SD patients who presented for botulinum toxin injections. One hundred forty-five SD patients (mean age 59.5 ± 13.6 years) had a general SE score (Cronbach's α = 0.894) of 33.4 ± 5.2 out of 40. This was negatively correlated with HADS-A (r = -0.42, P < 0.001) and HADS-D (r = -0.42, P < .001), but not correlated with VHI-10 (r = -0.098, P = .243) and CAPE-V (r = -0.047, P = .57). Factor analysis selected 8 items from the general SE scale and 5 disease-specific SE-SD items to generate a 13-item disease-specific SE-SD scale (Cronbach's α = 0.907). Disease-specific SE-SD score was 42.1 ± 6.9 out of 52 and was negatively correlated with VHI-10 (r = -0.19, P = .005), HADS-A (r = -0.43, P < .001), and HADS-D (r = -0.57, P < .001), but not correlated with CAPE-V (r = -0.024, P = .60). SD patients established on botulinum toxin injections have high degrees of general and disease-specific SE. Patients with higher SE-SD demonstrate lower vocal handicap and lower levels of anxiety and depression. A 13-item disease-specific SE-SD scale has been developed.

  20. The disease related deaths due to differentiated thyroid carcinomas treated multidisciplinary, including radioiodine

    International Nuclear Information System (INIS)

    Stefanovic, Lj.; Kermeci, K.; Malesevic, M.; Mihailovic, J.; Srbovan, D.; Popadic, S.

    2002-01-01

    Aim: To analyse the disease related deaths of differentiated thyroid carcinoma (DTC) patients treated multidisciplinary, including radioiodine. Patients and Methods: 364 DTC patients were treated from 1977 to the end of 2000. All patients were operated, treated by radioiodine and by hormonal therapy, external radiotherapy was applied in 22 and chemotherapy in 6 of them. 54 treated patients were lost from the follow-up. The course of disease and outcomes are known in 310 patients, among them 53 patients died. The disease related deaths occurred in 33 (10.6%) patients. Results: Between 33 patients whose deaths were in relation with DTC the disease progression was the cause of deaths in 30 (9.7% of treated) patients (the locoregional disease in 10, distant metastases /M1/ in 17, locoregional disease + M1 in 3 patients). From the late complications of treatment died 3 (1%) patients (all of them were in complete remission to the deaths). The mean survival of these 33 patients from the diagnosis to the end of the life was 6.9 years, median 5.1 years, range 2 months to 23.9 years. The five years survived 54.6% of them, 10 years 21.2% and more than 20 years 3%. M1 had 72.7% of patients (lung and/or bone M1 were present in 91.7% of them), N1 had 69.7% and in 30.3% local tumor was T4. In relation to all treated patients died 14.6% men compared to 9% women (p<0.05), 15.7% of patients 45 years old or older compared to 4.4% of younger then 45 years (p<0.001) and 21.3% of patients with follicular type of DTC compared to 7.3% with papillary type (p<0.001). From all patients without radioiodine accumulation in tumor tissue died 60%. Conclusion: The DTC related deaths were the consequence of M1 and less frequently the result of locoregional disease (T4 and/or N1) in about 1/10 of all treated patients. The deaths as result of the late complications of treatment were exceptional. The deaths were significantly more frequent between males, patients 45 years old or older and patients

  1. Automated real time constant-specificity surveillance for disease outbreaks

    Directory of Open Access Journals (Sweden)

    Brownstein John S

    2007-06-01

    Full Text Available Abstract Background For real time surveillance, detection of abnormal disease patterns is based on a difference between patterns observed, and those predicted by models of historical data. The usefulness of outbreak detection strategies depends on their specificity; the false alarm rate affects the interpretation of alarms. Results We evaluate the specificity of five traditional models: autoregressive, Serfling, trimmed seasonal, wavelet-based, and generalized linear. We apply each to 12 years of emergency department visits for respiratory infection syndromes at a pediatric hospital, finding that the specificity of the five models was almost always a non-constant function of the day of the week, month, and year of the study (p Conclusion Modeling the variance of visit patterns enables real-time detection with known, constant specificity at all times. With constant specificity, public health practitioners can better interpret the alarms and better evaluate the cost-effectiveness of surveillance systems.

  2. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  3. Development of disease-specific growth charts in Turner syndrome and Noonan syndrome

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Isojima

    2017-12-01

    Full Text Available Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

  4. Development of disease-specific growth charts in Turner syndrome and Noonan syndrome.

    Science.gov (United States)

    Isojima, Tsuyoshi; Yokoya, Susumu

    2017-12-01

    Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

  5. Short-term Evaluation of a Comprehensive Education Program Including Inhaler Training and Disease Management on Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Yoo, Kwang Ha; Chung, Wou Young; Park, Joo Hun; Hwang, Sung Chul; Kim, Tae Eun; Oh, Min Jung; Kang, Dae Ryong; Rhee, Chin Kook; Yoon, Hyoung Kyu; Kim, Tae Hyung; Kim, Deog Kyeom; Park, Yong Bum; Kim, Sang Ha; Yum, Ho Kee

    2017-10-01

    Proper education regarding inhaler usage and optimal management of chronic obstructive pulmonary disease (COPD) is essential for effectively treating patients with COPD. This study was conducted to evaluate the effects of a comprehensive education program including inhaler training and COPD management. We enlisted 127 patients with COPD on an outpatient basis at 43 private clinics in Korea. The patients were educated on inhaler usage and disease management for three visits across 2 weeks. Physicians and patients were administered a COPD assessment test (CAT) and questionnaires about the correct usage of inhalers and management of COPD before commencement of this program and after their third visit. The outcomes of 127 COPD patients were analyzed. CAT scores (19.6±12.5 vs. 15.1±12.3) improved significantly after this program (pmanagement and the correct technique for using inhalers than those who did not have improved CAT scores (peducation program including inhaler training and COPD management at a primary care setting improved CAT scores and led to patients' better understanding of COPD management. Copyright©2017. The Korean Academy of Tuberculosis and Respiratory Diseases

  6. Specific diagnosis of brain disease with double isotope brain scanning

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J; Lotritsch, K H; Hilbrand, E; Meixner, M; Barolin, G; Scholz, H [Landesunfallkrankenhaus, Feldkirch (Austria). Dept. of Nuclear Medicine; Landesnervenkrankenhaus, Feldkirch (Austria). Dept. of Neurology)

    1976-02-01

    25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double siotope imaging technique using sup(99m)TcO/sub 4/- and sup(99m)Tc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. sup(99m)Tc-EHDP is shown to be the tracer of choice for the imaging of CVA's and sup(99m)TcO/sub 4/- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain.

  7. Improving the Specificity of EEG for Diagnosing Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    François-B. Vialatte

    2011-01-01

    Full Text Available Objective. EEG has great potential as a cost-effective screening tool for Alzheimer's disease (AD. However, the specificity of EEG is not yet sufficient to be used in clinical practice. In an earlier study, we presented preliminary results suggesting improved specificity of EEG to early stages of Alzheimer's disease. The key to this improvement is a new method for extracting sparse oscillatory events from EEG signals in the time-frequency domain. Here we provide a more detailed analysis, demonstrating improved EEG specificity for clinical screening of MCI (mild cognitive impairment patients. Methods. EEG data was recorded of MCI patients and age-matched control subjects, in rest condition with eyes closed. EEG frequency bands of interest were θ (3.5–7.5 Hz, α1 (7.5–9.5 Hz, α2 (9.5–12.5 Hz, and β (12.5–25 Hz. The EEG signals were transformed in the time-frequency domain using complex Morlet wavelets; the resulting time-frequency maps are represented by sparse bump models. Results. Enhanced EEG power in the θ range is more easily detected through sparse bump modeling; this phenomenon explains the improved EEG specificity obtained in our previous studies. Conclusions. Sparse bump modeling yields informative features in EEG signal. These features increase the specificity of EEG for diagnosing AD.

  8. Cause-Specific Mortality Among Spouses of Parkinson Disease Patients

    DEFF Research Database (Denmark)

    Nielsen, Malene; Hansen, Jonni; Ritz, Beate

    2014-01-01

    BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson...... disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among...... men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1...

  9. Experiences of Students with Specific Learning Disorder (Including ADHD) in Online College Degree Programs: A Phenomenological Study

    Science.gov (United States)

    Bunch, Seleta LeAnn

    2016-01-01

    Enrollment in online degree programs is rapidly expanding due to the convenience and affordability offered to students and improvements in technology. The purpose of this hermeneutical phenomenological study was to understand the shared experiences of students with documented specific learning disorders (including Attention-Deficit/Hyperactivity…

  10. ALLERGEN-SPECIFIC IMMUNOTHERAPY: VACCINES FOR ALLERGIC DISEASES

    Directory of Open Access Journals (Sweden)

    A. S. Fedorov

    2015-01-01

    Full Text Available Allergen-specific immunotherapy (ASIT is the most effective method of allergy treatment which consists of exposure to small doses of antigen responsible for development of allergic condition in the particular patient. Therefore, one may achieve desensitization to this antigen. The history of ASIT application lasts for more than 100 years, and, over this time, huge clinical evidence for the usage of the method has been accumulated. Use of ASIT causes reduction of allergy symptoms and treatment needs and, moreover, it has the potential for long-term clinical benefit, by preventing the development of allergy and its symptoms. The treatment affects basic immunological mechanisms responsible for the development of clinical symptoms. ASIT is an antiinflammatory, pathogenetic and prophylactic treatment of allergic airway disease. The review considers the results of major clinical trials of the ASIT applications for treatment of allergic diseases of the respiratory system (allergic rhinitis and bronchial asthma. Various schemes of ASIT are discussed including its different variants (injectable and sublingual ASIT, the issues of preparation choice for ASIT from those currently available on the pharmaceutical market, patient selection criteria, and the issues of modern molecular allergodiagnostic (allergic sensitization mapping of the patient at molecular level, in order to optimize them. Immunological mechanisms of ASIT are also considered, since appropriate views are rather contraversial. The ASIT effect is mediated through the following basic immunological mechanisms: the suppressed increase of the eosinophil concentrations, reduced duration of the delayed hypersensitivity phase, as well as initiation and maintenance of the Th2-to-Th1-like immune response transition. Regulatory T-cells play a major role in implementation of the immunological mechanism in ASIT, they have a significant impact on the Th2 response suppression. Such suppression may proceed

  11. SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

    International Nuclear Information System (INIS)

    Short, Stephen; Malartre, Marianne; Sharpe, Colin

    2005-01-01

    SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box. The profile in mice includes an abundant, novel SMRT isoform that possesses just one CoRNR box. Mouse tissues therefore express SMRT isoforms containing one, two or three CoRNR boxes. In frogs, the SMRT isoform profile is tissue-specific. The mouse also shows distinct profiles generated by differential expression levels of the SMRT transcript isoforms. The formation of multiple SMRT isoforms and their tissue-specific regulation indicates a mechanism, whereby cells can define the repertoire of transcription factors regulated by SMRT

  12. Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific patterns?

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    ) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant...

  13. Clinicopathological review of immunohistochemically defined Kikuchi-Fujimoto disease-including some interesting cases.

    Science.gov (United States)

    Seong, Gil Myeong; Kim, Jo-Heon; Lim, Gil Chai; Kim, Jinseok

    2012-10-01

    Kikuchi-Fujimoto Disease (KFD) is a benign, self-limited disease characterized by tender regional lymphadenopathy with fever. KFD remains a poorly defined disease, and no clear diagnostic criteria are available. Here, we assess the clinical, laboratory, and histopathologic findings of KFD cases and report two unusual cases. Forty KFD patients that underwent lymph node (LN) biopsy and diagnosed by immunohistochemical staining, from January 2003 to November 2010, were enrolled in this retrospective study. The patients had a mean age of 29.3 years, and 29 (72.5 %) were women. Affected LNs were mainly located unilaterally in the cervical area. Mean LN size was 15.3 mm. Twenty-eight (70 %) patients had LN tenderness, and 25 (62.5 %) patients had fever. Leukopenia was observed in 18 of 35 evaluable patients. C-reactive protein and erythrocyte sedimentation rate were elevated in most patients. Anti-nuclear antibody was positive in four of 19 evaluable patients, but all had been diagnosed with concurrent systemic lupus erythematosus. Histologically, the 40 cases were classified into three types, that is, as proliferative (37.5 %), necrotizing (55.0 %), or xanthomatous (7.5 %). Interesting cases: Case 1 was a 35-year-old female with KFD and uveitis, retinal vasculitis, and superior sagittal sinus thrombosis. Case 2 was a 47-year-old male with KFD and bone marrow involvement and presented with severe bicytopenia. Although KFD is an uncommon self-limited benign disorder, it must be included in the differential diagnosis of lymphadenopathy with fever and cytopenia. It is important that the clinical features of KFD be understood to reach a correct diagnosis.

  14. Automated real time constant-specificity surveillance for disease outbreaks.

    Science.gov (United States)

    Wieland, Shannon C; Brownstein, John S; Berger, Bonnie; Mandl, Kenneth D

    2007-06-13

    For real time surveillance, detection of abnormal disease patterns is based on a difference between patterns observed, and those predicted by models of historical data. The usefulness of outbreak detection strategies depends on their specificity; the false alarm rate affects the interpretation of alarms. We evaluate the specificity of five traditional models: autoregressive, Serfling, trimmed seasonal, wavelet-based, and generalized linear. We apply each to 12 years of emergency department visits for respiratory infection syndromes at a pediatric hospital, finding that the specificity of the five models was almost always a non-constant function of the day of the week, month, and year of the study (p accounting for not only the expected number of visits, but also the variance of the number of visits. The expectation-variance model achieves constant specificity on all three time scales, as well as earlier detection and improved sensitivity compared to traditional methods in most circumstances. Modeling the variance of visit patterns enables real-time detection with known, constant specificity at all times. With constant specificity, public health practitioners can better interpret the alarms and better evaluate the cost-effectiveness of surveillance systems.

  15. Hip and pelvis diseases on lumbar AP radiographs including both hip joints

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Soo; Juhng, Seon Kwan; Kim, Eun A; Kim, Jeong Ho; Song, Ha Heon; Shim, Dae Moo [Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2002-12-01

    To determine the frequency of disease, and to evaluate the methods used for lumbar spine radiography in Korea. Sixty university and training hospitals were randomly selected and asked to describe the projections, film size and radiographic techniques employed for routine radiography in patients with suspected disease of the lumbar spine. Plain radiographs of 1215 patients, taken using 14x17 inch film and depicting both hip joints and the lumbar region, were analysed between March 1999 and February 2000. In 15 patients (1.2%), the radiographs revealed hip or pelvic lesion, confirmed as follows: avascular necrosis of the femoral head (n=11, with bilateral lesion in four cases); sustained ankylosing spondylitis (n=2); acetabular dysplasia (n=1); and insufficiency fracture of the pubic rami secondary to osteoporosis (n=1). In 11 or the 20 hospitals which responded, 14{sup x}17{sup f}ilm was being used for lumbar radiography, while in the other nine, film size was smaller. Plain radiography of the lumbar spine including both hip joints, may be a useful way to simultaneously evaluate lesions not only of the lumbar spine but also of the hip and/or pelvis.

  16. Broader prevalence of Wolbachia in insects including potential human disease vectors.

    Science.gov (United States)

    de Oliveira, C D; Gonçalves, D S; Baton, L A; Shimabukuro, P H F; Carvalho, F D; Moreira, L A

    2015-06-01

    Wolbachia are intracellular, maternally transmitted bacteria considered the most abundant endosymbionts found in arthropods. They reproductively manipulate their host in order to increase their chances of being transmitted to the offspring, and currently are being used as a tool to control vector-borne diseases. Studies on distribution of Wolbachia among its arthropod hosts are important both for better understanding why this bacterium is so common, as well as for its potential use as a biological control agent. Here, we studied the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in terms of their sensitivity to detect this bacterium. The overall incidence of Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The most common positive insect orders were Coleoptera, Diptera, Hemiptera and Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia-positive families. They included potential human disease vectors whose infection status has never been reported before. Our study further shows the importance of using quantitative polymerase chain reaction for high-throughput and sensitive Wolbachia screening.

  17. Specific balance training included in an endurance-resistance exercise program improves postural balance in elderly patients undergoing haemodialysis.

    Science.gov (United States)

    Frih, Bechir; Mkacher, Wajdi; Jaafar, Hamdi; Frih, Ameur; Ben Salah, Zohra; El May, Mezry; Hammami, Mohamed

    2018-04-01

    The purpose of this study was to evaluate the effects of 6 months of specific balance training included in endurance-resistance program on postural balance in haemodialysis (HD) patients. Forty-nine male patients undergoing HD were randomly assigned to an intervention group (balance training included in an endurance-resistance training, n = 26) or a control group (resistance-endurance training only, n = 23). Postural control was assessed using six clinical tests; Timed Up and Go test, Tinetti Mobility Test, Berg Balance Scale, Unipodal Stance test, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scale. All balance measures increased significantly after the period of rehabilitation training in the intervention group. Only the Timed Up and Go, Berg Balance Scale, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scores were improved in the control group. The ranges of change in these tests were greater in the balance training group. In HD patients, specific balance training included in a usual endurance-resistance training program improves static and dynamic balance better than endurance-resistance training only. Implications for rehabilitation Rehabilitation using exercise in haemodialysis patients improved global mobility and functional abilities. Specific balance training included in usual endurance resistance training program could lead to improved static and dynamic balance.

  18. Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A Multicenter Cohort Study

    Directory of Open Access Journals (Sweden)

    Min Ji Jeon

    2017-11-01

    Full Text Available BackgroundLittle is known regarding disease-specific mortality of differentiated thyroid cancer (DTC patients and its risk factors in Korea.MethodsWe retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005.ResultsMean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97% and underwent total thyroidectomy (85%. Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9% occurred; the 10-year disease-specific survival (DSS rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%. Older age (≥45 years at diagnosis, male, follicular thyroid cancer (FTC versus PTC, larger tumor size (>2 cm, presence of extrathyroidal extension (ETE, lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM stage were independent risk factors of disease-specific mortality of DTC patients.ConclusionThe rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients.

  19. Enteroclysis in adult celiac disease: diagnostic value of specific radiographic features

    International Nuclear Information System (INIS)

    Lomoschitz, F.; Schima, W.; Schober, E.; Turetschek, K.; Kaider, A.; Vogelsang, H.

    2003-01-01

    The purpose of this study was to compare the diagnostic accuracy of various radiographic findings at enteroclysis in adult patients with untreated celiac disease. Twenty-seven adult patients underwent enteroclysis because of unspecific intestinal symptoms before definitive biopsy proof of celiac disease. Enteroclysis of 123 subjects with similar clinical presentation, including abdominal pain, diarrhea, occult intestinal bleeding, and weight loss, who had a definitive diagnosis other than celiac disease, served as controls. The radiographic features previously described in the literature as indicative of adult celiac disease (i.e., fold thickening, decrease of jejunal folds, increase of ileal folds, small bowel dilatation, flocculation) were evaluated in blinded fashion in all studies and the subjective likelihood of diagnosis of celiac disease was assessed. Assessing every finding separately, each feature proved to have a high specificity (78-100%) but low sensitivity (19-59%) for celiac disease. Reversal of jejunoileal fold pattern was the single best feature (specificity 100%, 95% CI 97-100%; sensitivity 59%, 95% CI 40-78%); however, combination of criteria enables establishment of the diagnosis of celiac disease quite accurately (specificity 100%, 95% CI 98-100%; sensitivity 78%, 95% CI 58-91%). Reversal of jejunoileal fold pattern as a single finding as well as combination at least three of the following features, i.e., fold thickening, decrease of jejunal folds (''colonization''), increase of ileal folds (''jejunization''), dilatation, and flocculation, make enteroclysis an accurate tool for diagnosis of celiac disease in adult patients with suspected intestinal disease. (orig.)

  20. Efficacy of a Multimodal Cognitive Rehabilitation Including Psychomotor and Endurance Training in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    I. Reuter

    2012-01-01

    Full Text Available Mild cognitive impairment, especially executive dysfunction might occur early in the course of Parkinson's disease. Cognitive training is thought to improve cognitive performance. However, transfer of improvements achieved in paper and pencil tests into daily life has been difficult. The aim of the current study was to investigate whether a multimodal cognitive rehabilitation programme including physical exercises might be more successful than cognitive training programmes without motor training. 240 PD-patients were included in the study and randomly allocated to three treatment arms, group A cognitive training, group B cognitive training and transfer training and group C cognitive training, transfer training and psychomotor and endurance training. The primary outcome measure was the ADAS-Cog. The secondary outcome measure was the SCOPA-Cog. Training was conducted for 4 weeks on a rehabilitation unit, followed by 6 months training at home. Caregivers received an education programme. The combination of cognitive training using paper and pencil and the computer, transfer training and physical training seems to have the greatest effect on cognitive function. Thus, patients of group C showed the greatest improvement on the ADAS-Cog and SCOPA-COG and were more likely to continue with the training programme after the study.

  1. Tract specific analysis in patients with sickle cell disease

    Science.gov (United States)

    Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

    2015-12-01

    Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

  2. Future arrangements for Great Britain's gas quality specifications. Government Response (including Summary of Responses) to consultation on future arrangements for Great Britain's gas quality specifications

    International Nuclear Information System (INIS)

    2007-01-01

    Last year the Government consulted on GB's future gas quality specifications. The background is that some streams of imported gases have an energy content that exceeds the upper limit specified in GB's current gas quality regulations. The policy issue was whether to stick with the current regulated specifications, but at the cost of having to process imported gas to bring it within those specifications; or, at some time after 2020, to adjust those specifications, but at the cost of having to check (and potentially change) approximately 45m domestic gas appliances in 22m households, to ensure that they are capable of burning the high energy gas safely (and with a residual safety risk that some appliances are missed). The Consultation Document sought views on the proposal (backed up by the Partial Regulatory Impact Assessment) to adopt the 'no change' option. In the light of the responses, this is what the Government now proposes. The associated Impact Assessment estimates the total net benefit of the 'no change' option at UK Pounds 1.5bn - 14bn, with a best estimate of UK Pounds 8bn (NPV, 2005). The risks for gas prices and security of supply (included in the Impact Assessment) are judged to be small. The Government proposes a 'forward plan', consisting of support for Ofgem's work on maximising the commercial flexibilities for the GB gas market to handle gases of different specifications, whilst continuing to engage in EU discussions on the gas quality issue. (Author)

  3. A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Seonmi Park

    2017-04-01

    Full Text Available Summary: Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes, and fetal hemoglobin (HbF levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS mutation. : In this resource article, Mostoslavsky, Murphy, and colleagues of the NextGen consortium describe a diverse, comprehensive, and characterized library of sickle cell disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes and fetal hemoglobin (HbF levels. This bank is readily available and accessible to all investigators. Keywords: induced pluripotent stem cells, iPSCs, sickle cell disease, disease modeling, directed differentiation, gene correction

  4. Cost of tobacco-related diseases, including passive smoking, in Hong Kong.

    Science.gov (United States)

    McGhee, S M; Ho, L M; Lapsley, H M; Chau, J; Cheung, W L; Ho, S Y; Pow, M; Lam, T H; Hedley, A J

    2006-04-01

    Costs of tobacco-related disease can be useful evidence to support tobacco control. In Hong Kong we now have locally derived data on the risks of smoking, including passive smoking. To estimate the health-related costs of tobacco from both active and passive smoking. Using local data, we estimated active and passive smoking-attributable mortality, hospital admissions, outpatient, emergency and general practitioner visits for adults and children, use of nursing homes and domestic help, time lost from work due to illness and premature mortality in the productive years. Morbidity risk data were used where possible but otherwise estimates based on mortality risks were used. Utilisation was valued at unit costs or from survey data. Work time lost was valued at the median wage and an additional costing included a value of USD 1.3 million for a life lost. In the Hong Kong population of 6.5 million in 1998, the annual value of direct medical costs, long term care and productivity loss was USD 532 million for active smoking and USD 156 million for passive smoking; passive smoking accounted for 23% of the total costs. Adding the value of attributable lives lost brought the annual cost to USD 9.4 billion. The health costs of tobacco use are high and represent a net loss to society. Passive smoking increases these costs by at least a quarter. This quantification of the costs of tobacco provides strong motivation for legislative action on smoke-free areas in the Asia Pacific Region and elsewhere.

  5. Including refugees in disease elimination: challenges observed from a sleeping sickness programme in Uganda.

    Science.gov (United States)

    Palmer, Jennifer J; Robert, Okello; Kansiime, Freddie

    2017-01-01

    Ensuring equity between forcibly-displaced and host area populations is a key challenge for global elimination programmes. We studied Uganda's response to the recent refugee influx from South Sudan to identify key governance and operational lessons for national sleeping sickness programmes working with displaced populations today. A refugee policy which favours integration of primary healthcare services for refugee and host populations and the availability of rapid diagnostic tests (RDTs) to detect sleeping sickness at this health system level makes Uganda well-placed to include refugees in sleeping sickness surveillance. Using ethnographic observations of coordination meetings, review of programme data, interviews with sleeping sickness and refugee authorities and group discussions with health staff and refugees (2013-2016), we nevertheless identified some key challenges to equitably integrating refugees into government sleeping sickness surveillance. Despite fears that refugees were at risk of disease and posed a threat to elimination, six months into the response, programme coordinators progressed to a sentinel surveillance strategy in districts hosting the highest concentrations of refugees. This meant that RDTs, the programme's primary surveillance tool, were removed from most refugee-serving facilities, exacerbating existing inequitable access to surveillance and leading refugees to claim that their access to sleeping sickness tests had been better in South Sudan. This was not intentionally done to exclude refugees from care, rather, four key governance challenges made it difficult for the programme to recognise and correct inequities affecting refugees: (a) perceived donor pressure to reduce the sleeping sickness programme's scope without clear international elimination guidance on surveillance quality; (b) a problematic history of programme relations with refugee-hosting districts which strained supervision of surveillance quality; (c) difficulties that

  6. Newcastle disease: An in-depth review including epidemiology and molecular diagnostics

    Science.gov (United States)

    Infections of birds with strains of avian paramyxovirus serotype 1 (APMV-1), (synonyms: Newcastle disease virus (NDV), pigeon PMV-1 (PPMV-1)) are associated with two clinical outcomes: 1) Newcastle disease (ND) results from infections with virulent APMV-1, and is also called Exotic ND (END) in U. S...

  7. Assessment of disease-specific knowledge in Australian children with inflammatory bowel disease and their parents.

    Science.gov (United States)

    Day, Andrew S; Mylvaganam, Gaithri; Shalloo, Nollaig; Clarkson, Cathy; Leach, Steven T; Lemberg, Daniel A

    2017-08-01

    Disease-specific knowledge may influence disease outcome and quality of life in children with inflammatory bowel disease (IBD). This prospective study aimed to define IBD-related knowledge in a group of Australian children with IBD and their parents using a validated measure of disease-specific knowledge, the Inflammatory Bowel Disease Knowledge Inventory Device (IBD-KID). Children (less than 18 years) diagnosed with IBD who were members of the Australian patient support organisation were identified. Each family was sent copies of the IBD-KID. Children aged 10-18 years and all parents were asked to complete the IBD-KID and to also provide demographic details and disease characteristics. Replies were received from 196 families: 262 parents and 128 children completed questionnaires. Most children had a diagnosis of Crohn disease (65%) and 51% were male. Children diagnosed in the preceding 6 years scored higher than those with longer time since diagnosis. Parents had better scores in the IBD-KID than the children (P parents and children had poor understanding of key management issues for IBD (such as side effects of steroids), important outcomes (e.g. growth) and the use of complementary therapies. Consistent patterns of IBD-related knowledge were noted in this large group of Australian children with IBD and their parents. Measurement of disease-related knowledge with the IBD-KID can identify gaps in understanding, thereby permitting focused educational activities. Although these knowledge gaps may impact upon outcomes, further prospective studies are now required to elucidate the relationships between enhanced knowledge and specific outcomes. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  8. The impact of strain-specific immunity on Lyme disease incidence is spatially heterogeneous.

    Science.gov (United States)

    Khatchikian, Camilo E; Nadelman, Robert B; Nowakowski, John; Schwartz, Ira; Wormser, Gary P; Brisson, Dustin

    2017-12-01

    Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne infection in the US. Recent studies have demonstrated that the incidence of human Lyme disease would have been even greater were it not for the presence of strain-specific immunity, which protects previously infected patients against subsequent infections by the same B. burgdorferi strain. Here, spatial heterogeneity is incorporated into epidemiological models to accurately estimate the impact of strain-specific immunity on human Lyme disease incidence. The estimated reduction in the number of Lyme disease cases is greater in epidemiologic models that explicitly include the spatial distribution of Lyme disease cases reported at the county level than those that utilize nationwide data. strain-specific immunity has the greatest epidemiologic impact in geographic areas with the highest Lyme disease incidence due to the greater proportion of people that have been previously infected and have developed strain-specific immunity. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Capturing structured, pulmonary disease-specific data elements in electronic health records.

    Science.gov (United States)

    Gronkiewicz, Cynthia; Diamond, Edward J; French, Kim D; Christodouleas, John; Gabriel, Peter E

    2015-04-01

    Electronic health records (EHRs) have the potential to improve health-care quality by allowing providers to make better decisions at the point of care based on electronically aggregated data and by facilitating clinical research. These goals are easier to achieve when key, disease-specific clinical information is documented as structured data elements (SDEs) that computers can understand and process, rather than as free-text/natural-language narrative. This article reviews the benefits of capturing disease-specific SDEs. It highlights several design and implementation considerations, including the impact on efficiency and expressivity of clinical documentation and the importance of adhering to data standards when available. Pulmonary disease-specific examples of collection instruments are provided from two commonly used commercial EHRs. Future developments that can leverage SDEs to improve clinical quality and research are discussed.

  10. Disease-specific health status as a predictor of mortality in patients with heart failure

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H; Versteeg, Henneke; Zijlstra, Wobbe P

    2014-01-01

    AIMS: Some, but not all, studies have shown that patient-reported health status, including symptoms, functioning, and health-related quality of life, provides additional information to traditional clinical factors in predicting prognosis in heart failure patients. To evaluate the overall evidence......, the association of disease-specific health status on mortality in heart failure was examined through a systematic review and meta-analysis. METHODS AND RESULTS: Prospective cohort studies that assessed the independent association of disease-specific health status with mortality in heart failure were selected....... Searching PubMed (until March 2013) resulted in 17 articles in the systematic review and 17 studies in the meta-analysis. About half of the studies reported a significant relationship between disease-specific health status and mortality in heart failure, while the remainder found no association. A larger...

  11. Specific schistosomiasis treatment as a strategy for disease control

    Directory of Open Access Journals (Sweden)

    José Rodrigues Coura

    2010-07-01

    Full Text Available The great hope for schistosomiasis treatment began with the development of oxamniquine and praziquantel. These drugs can be administered orally in a single dose and have a high curative power with minor side effects. In this study, we carried out a field experiment involving a population of 3,782 people. The population was examined at four localities in Minas Gerais within the valleys of the Doce and Jequitinhonha Rivers. In this cohort, there were 1,790 patients infected with Schistosoma mansoni (47.3% and we showed that only 1,403 (78.4% could be treated with oxamniquine in a single dose of 12.5-20 mg/kg orally. The other 387 (21.6% were not treated during the first stage because of contraindications (pregnancy or impeditive diseases, absences or refusals. It was observed that, on average, 8.8-17% of the infected patients continued to excrete S. mansoni eggs at the end of the 2nd month after treatment and 30-32% of the cohort was infected by the end of the 24th month. In one of the areas that we followed-up for a total of 30 years, the prevalence of the infection with S. mansoni fell from 60.8-19.3% and the hepatosplenic form of the disease dropped from 5.8-1.3%. We conclude that specific treatment of schistosomiasis reduces the prevalence of infection in the short-term and the morbidity due to schistosomiasis in medium to long-term time frames, but does not help to control disease transmission.

  12. ADO: a disease ontology representing the domain knowledge specific to Alzheimer's disease.

    Science.gov (United States)

    Malhotra, Ashutosh; Younesi, Erfan; Gündel, Michaela; Müller, Bernd; Heneka, Michael T; Hofmann-Apitius, Martin

    2014-03-01

    Biomedical ontologies offer the capability to structure and represent domain-specific knowledge semantically. Disease-specific ontologies can facilitate knowledge exchange across multiple disciplines, and ontology-driven mining approaches can generate great value for modeling disease mechanisms. However, in the case of neurodegenerative diseases such as Alzheimer's disease, there is a lack of formal representation of the relevant knowledge domain. Alzheimer's disease ontology (ADO) is constructed in accordance to the ontology building life cycle. The Protégé OWL editor was used as a tool for building ADO in Ontology Web Language format. ADO was developed with the purpose of containing information relevant to four main biological views-preclinical, clinical, etiological, and molecular/cellular mechanisms-and was enriched by adding synonyms and references. Validation of the lexicalized ontology by means of named entity recognition-based methods showed a satisfactory performance (F score = 72%). In addition to structural and functional evaluation, a clinical expert in the field performed a manual evaluation and curation of ADO. Through integration of ADO into an information retrieval environment, we show that the ontology supports semantic search in scientific text. The usefulness of ADO is authenticated by dedicated use case scenarios. Development of ADO as an open ADO is a first attempt to organize information related to Alzheimer's disease in a formalized, structured manner. We demonstrate that ADO is able to capture both established and scattered knowledge existing in scientific text. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  13. Variation of a test’s sensitivity and specificity with disease prevalence

    Science.gov (United States)

    Leeflang, Mariska M.G.; Rutjes, Anne W.S.; Reitsma, Johannes B.; Hooft, Lotty; Bossuyt, Patrick M.M.

    2013-01-01

    Background: Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. Methods: We used data from 23 meta-analyses, each of which included 10–39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Results: Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p disease prevalence; there was no such systematic effect for sensitivity. Interpretation: The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation. PMID:23798453

  14. A 2-d classification of diseases based on age-specific death rates

    Science.gov (United States)

    Richmond, Peter; Roehner, Bertrand M.

    2018-02-01

    Age specific mortality curves exhibit an age tc (about 10 years) which plays a crucial role in that the mortality curve decreases hyperbolically in the age interval A before tc and increases exponentially in the interval B following tc. For those familiar with reliability theory, region A is called the "burn in" phase and B is the "wear out" phase. Using the exponents of the hyperbolic and exponential phases, we introduce a new 2 dimensional map of diseases. This permits the classification of diseases into three broad classes: AS1, AS2 and S. Class AS1 includes all diseases arising from congenital malformations which dominate infant and child mortality; class AS2 includes degenerative diseases such as dementia and Alzheimer's which dominate old age mortality. In class S, which includes most infectious and metabolic diseases, the exponents from both aging phases contribute to positions on the map. Cancer is one of these mixed cases but is closer to class AS2 than AS1. A second line classification is needed to resolve S cases and to this end we introduce a 3rd dimension, namely (calendar) time. Using historical data we show that in their response to treatment (particularly vaccination), S diseases fall into three sub-classes. (i) Class E diseases (e.g. measles or meningococcal disease) which have been almost eliminated at all ages (ii) class C diseases (e.g. tuberculosis) which can be cured but whose cure becomes less effective at old age. (iii) Class U diseases for which radical cures are still unknown. Regarding the future, the fact that the wear-out process of numerous diseases already starts around the age of 25 means that a major extension of the human lifespan beyond 120 certainly also requires to uncover the secret of the "elixir of eternal youth" which has driven timeless human efforts and still seems unlikely in the foreseeable future.

  15. Extensions of the Rosner-Colditz breast cancer prediction model to include older women and type-specific predicted risk.

    Science.gov (United States)

    Glynn, Robert J; Colditz, Graham A; Tamimi, Rulla M; Chen, Wendy Y; Hankinson, Susan E; Willett, Walter W; Rosner, Bernard

    2017-08-01

    A breast cancer risk prediction rule previously developed by Rosner and Colditz has reasonable predictive ability. We developed a re-fitted version of this model, based on more than twice as many cases now including women up to age 85, and further extended it to a model that distinguished risk factor prediction of tumors with different estrogen/progesterone receptor status. We compared the calibration and discriminatory ability of the original, the re-fitted, and the type-specific models. Evaluation used data from the Nurses' Health Study during the period 1980-2008, when 4384 incident invasive breast cancers occurred over 1.5 million person-years. Model development used two-thirds of study subjects and validation used one-third. Predicted risks in the validation sample from the original and re-fitted models were highly correlated (ρ = 0.93), but several parameters, notably those related to use of menopausal hormone therapy and age, had different estimates. The re-fitted model was well-calibrated and had an overall C-statistic of 0.65. The extended, type-specific model identified several risk factors with varying associations with occurrence of tumors of different receptor status. However, this extended model relative to the prediction of any breast cancer did not meaningfully reclassify women who developed breast cancer to higher risk categories, nor women remaining cancer free to lower risk categories. The re-fitted Rosner-Colditz model has applicability to risk prediction in women up to age 85, and its discrimination is not improved by consideration of varying associations across tumor subtypes.

  16. Enteroclysis in adult celiac disease: diagnostic value of specific radiographic features

    Energy Technology Data Exchange (ETDEWEB)

    Lomoschitz, F.; Schima, W.; Schober, E.; Turetschek, K. [Department of Radiology and Ludwig Boltzmann Institute for Clinical and Experimental Radiologic Research, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Kaider, A. [Department of Medical Computer Sciences, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Vogelsang, H. [Department of Internal Medicine IV, Division of Gastroenterology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2003-04-01

    The purpose of this study was to compare the diagnostic accuracy of various radiographic findings at enteroclysis in adult patients with untreated celiac disease. Twenty-seven adult patients underwent enteroclysis because of unspecific intestinal symptoms before definitive biopsy proof of celiac disease. Enteroclysis of 123 subjects with similar clinical presentation, including abdominal pain, diarrhea, occult intestinal bleeding, and weight loss, who had a definitive diagnosis other than celiac disease, served as controls. The radiographic features previously described in the literature as indicative of adult celiac disease (i.e., fold thickening, decrease of jejunal folds, increase of ileal folds, small bowel dilatation, flocculation) were evaluated in blinded fashion in all studies and the subjective likelihood of diagnosis of celiac disease was assessed. Assessing every finding separately, each feature proved to have a high specificity (78-100%) but low sensitivity (19-59%) for celiac disease. Reversal of jejunoileal fold pattern was the single best feature (specificity 100%, 95% CI 97-100%; sensitivity 59%, 95% CI 40-78%); however, combination of criteria enables establishment of the diagnosis of celiac disease quite accurately (specificity 100%, 95% CI 98-100%; sensitivity 78%, 95% CI 58-91%). Reversal of jejunoileal fold pattern as a single finding as well as combination at least three of the following features, i.e., fold thickening, decrease of jejunal folds (''colonization''), increase of ileal folds (''jejunization''), dilatation, and flocculation, make enteroclysis an accurate tool for diagnosis of celiac disease in adult patients with suspected intestinal disease. (orig.)

  17. Preferred SH3 domain partners of ADAM metalloproteases include shared and ADAM-specific SH3 interactions.

    Directory of Open Access Journals (Sweden)

    Iivari Kleino

    Full Text Available A disintegrin and metalloproteinases (ADAMs constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3 domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior.

  18. Development of a disease-specific quality of life questionnaire in Addison's disease.

    Science.gov (United States)

    Løvås, Kristian; Curran, Suzanne; Oksnes, Marianne; Husebye, Eystein S; Huppert, Felicia A; Chatterjee, V Krishna K

    2010-02-01

    Patients with Addison's disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL). We sought to develop an Addison's disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects. Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addison's disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addison's outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbach's alpha and Rasch analysis. Published studies of HRQoL in Addison's disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbach's alpha 0.95 and Person Separation Index 0.94 (Rasch analysis). We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addison's disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL).

  19. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

    Directory of Open Access Journals (Sweden)

    Xia Wang

    Full Text Available When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42 of the unsolved cases.Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

  20. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

    Directory of Open Access Journals (Sweden)

    David C Geary

    2016-04-01

    Full Text Available Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play and cognitive (e.g., language fluency traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments.

  1. Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases.

    Science.gov (United States)

    Fridkis-Hareli, Masha

    2008-02-15

    Organ-specific autoimmune diseases affect particular targets in the body, whereas systemic diseases engage multiple organs. Both types of autoimmune diseases may coexist in the same patient, either sequentially or concurrently, sustained by the presence of autoantibodies directed against the corresponding autoantigens. Multiple factors, including those of immunological, genetic, endocrine and environmental origin, contribute to the above condition. Due to association of certain autoimmune disorders with HLA alleles, it has been intriguing to examine the immunogenetic basis for autoantigen presentation leading to the production of two or more autoantibodies, each distinctive of an organ-specific or systemic disease. This communication offers the explanation for shared autoimmunity as illustrated by organ-specific blistering diseases and the connective tissue disorders of systemic nature. Several hypothetical mechanisms implicating HLA determinants, autoantigenic peptides, T cells, and B cells have been proposed to elucidate the process by which two autoimmune diseases are induced in the same individual. One of these scenarios, based on the assumption that the patient carries two disease-susceptible HLA genes, arises when a single T cell epitope of each autoantigen recognizes its HLA protein, leading to the generation of two types of autoreactive B cells, which produce autoantibodies. Another mechanism functioning whilst an epitope derived from either autoantigen binds each of the HLA determinants, resulting in the induction of both diseases by cross-presentation. Finally, two discrete epitopes originating from the same autoantigen may interact with each of the HLA specificities, eliciting the production of both types of autoantibodies. Despite the lack of immediate or unequivocal experimental evidence supporting the present hypothesis, several approaches may secure a better understanding of shared autoimmunity. Among these are animal models expressing the transgenes

  2. Quality of life in patients with anorectal malformation or Hirschsprung's disease: development of a disease-specific questionnaire

    NARCIS (Netherlands)

    Hanneman, M. J.; Sprangers, M. A.; de Mik, E. L.; Ernest van Heurn, L. W.; de Langen, Z. J.; Looyaard, N.; Madern, G. C.; Rieu, P. N.; van der Zee, D. C.; van Silfhout, M.; Aronson, D. C.

    2001-01-01

    PURPOSE: Hirschsprung's disease and anorectal malformation are congenital diseases of the digestive tract with sequelae into adulthood. The quality of life of patients with these diseases is largely unknown. The aim of the study was 1) to construct a self-report disease-specific instrument to assess

  3. 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...

  4. 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...

  5. Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and behaviour in younger patients with Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Bogdanos Dimitrios P

    2012-08-01

    Full Text Available Abstract Background Glycoprotein 2 (GP2 was discovered as the major autoantigen of Crohn’s disease (CD-specific pancreatic autoantibodies (PAB. We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes. Methods Anti-GP2 and anti-Saccharomyces cerevisiae (ASCA IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF in 271 sera, 169 with CD and 102 with ulcerative colitis (UC. As healthy controls 160 adult blood donors and 65 children were included. Results Anti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2% than in UC (9/102, 8.9% patients and in controls (9/225, 4% (p  Conclusions Anti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.

  6. The Impact of Chronic Skin Disease on Daily Life (ISDL): a generic and dermatology-specific health instrument.

    NARCIS (Netherlands)

    Evers, A.W.M.; Duller, P.; Kerkhof, P.C.M. van de; Valk, P.G.M. van der; Jong, E.M.G.J. de; Gerritsen, M.J.P.; Otero, E.; Verhoeven, E.W.M.; Verhaak, C.M.; Kraaimaat, F.W.

    2008-01-01

    BACKGROUND: In dermatological research and clinical practice, there is a need for comprehensive self-report instruments that assess a broad spectrum of health implications of chronic skin diseases, including generic and skin-specific aspects of disease-related quality of life. The advantages of

  7. Exploring the potential relevance of human-specific genes to complex disease

    Directory of Open Access Journals (Sweden)

    Cooper David N

    2011-01-01

    Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

  8. Are NOD2 polymorphisms linked to a specific disease endophenotype of Crohn's disease?

    DEFF Research Database (Denmark)

    Jensen, Stina Rikke; Nielsen, Ole Haagen; Pedersen, Susanne Brix

    2011-01-01

    is not yet clarified. The enhanced number of pathogenic E. coli in the ileal mucosa of CD as compared to healthy controls may result from a genetically based failure in one of the intestinal bacteria sensing systems, like NOD2, making the ileal epithelium more prone to colonization with microbes harboring...... specific properties such as AIEC. Increasing the focus on defining subgroups of patients with similar disease initiations, mechanisms of action, and manifestations in CD may be pivotal for the development and implementation of future individualized treatment strategies of benefit for the single patient...

  9. A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Park, Seonmi; Gianotti-Sommer, Andreia; Molina-Estevez, Francisco Javier; Vanuytsel, Kim; Skvir, Nick; Leung, Amy; Rozelle, Sarah S; Shaikho, Elmutaz Mohammed; Weir, Isabelle; Jiang, Zhihua; Luo, Hong-Yuan; Chui, David H K; Figueiredo, Maria Stella; Alsultan, Abdulraham; Al-Ali, Amein; Sebastiani, Paola; Steinberg, Martin H; Mostoslavsky, Gustavo; Murphy, George J

    2017-04-11

    Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide

    Science.gov (United States)

    Hajipour, Mohammad Javad; Raheb, Jamshid; Akhavan, Omid; Arjmand, Sareh; Mashinchian, Omid; Rahman, Masoud; Abdolahad, Mohammad; Serpooshan, Vahid; Laurent, Sophie; Mahmoudi, Morteza

    2015-05-01

    The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred to as the `personalized protein corona'). In this study, we demonstrate that graphene oxide (GO) sheets can trigger different biological responses in the presence of coronas obtained from various types of diseases. GO sheets were incubated with plasma from human subjects with different diseases/conditions, including hypofibrinogenemia, blood cancer, thalassemia major, thalassemia minor, rheumatism, fauvism, hypercholesterolemia, diabetes, and pregnancy. Identical sheets coated with varying protein corona decorations exhibited significantly different cellular toxicity, apoptosis, and uptake, reactive oxygen species production, lipid peroxidation and nitrogen oxide levels. The results of this report will help researchers design efficient and safe, patient-specific nano biomaterials in a disease type-specific manner for clinical and biological applications.The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred

  11. Clinical validity of a disease-specific health status questionnaire: the peripheral artery questionnaire.

    Science.gov (United States)

    Hoeks, Sanne E; Smolderen, Kim G; Scholte Op Reimer, Wilma J M; Verhagen, Hence J M; Spertus, John A; Poldermans, Don

    2009-02-01

    Measuring patient-centered outcomes is becoming increasingly important in patients with peripheral arterial disease (PAD), both as a means of determining the benefits of treatment and as an aid for disease management. In order to monitor health status in a reliable and sensitive way, the disease-specific measure Peripheral Artery Questionnaire (PAQ) was developed. However, to date, its correlation with traditional clinical indices is unknown. The primary aim of this study was to better establish the clinical validity of the PAQ by examining its association with functional indices related to PAD. Furthermore, we hypothesized that the clinical validity of this disease-specific measure is better as compared with the EuroQol-5-dimensional (EQ-5D), a standardized generic instrument. Data on 711 consecutive PAD patients undergoing surgery were collected from 11 Dutch hospitals in 2004. At 3-year follow-up, questionnaires including the PAQ, EQ-5D, and EuroQol-Visual Analogue Scale (EQ VAS) were completed in 84% of survivors. The PAQ was analyzed according to three domains, as established by a factor analyses in the Dutch population, and the summary score. Baseline clinical indices included the presence and severity of claudication intermittent (CI) and the Lee Cardiac Risk Index. All three PAQ domains (Physical Function, Perceived Disability, and Treatment Satisfaction) were significantly associated with CI symptoms (P values PAQ summary scores as compared with asymptomatic patients (58.6 +/- 27.8 vs 68.6 +/- 27.8, P = PAQ summary score and the subscale scores for Physical Functioning and Perceived Disability demonstrated a clear dose-response relation for walking distance and the Lee Risk Index (P values PAQ proved to be good as the PAQ subscales discriminated well between patients with or without symptomatic PAD and its severity as defined by walking distance. Furthermore, the PAQ subscales were directly proportional to the presence and number of risk factors relevant

  12. The stress of being chronically ill: from disease-specific to task-specific aspects.

    NARCIS (Netherlands)

    Heijmans, M.; Rijken, M.; Foets, M.; Ridder, D. de; Schreurs, K.; Bensing, J.

    2004-01-01

    The assumption that disease-related stressors are exclusive for particular diagnoses characterizes many studies of chronically ill patients. In this study the perceptions of 1305 patients from 10 different chronic disease categories were compared with respect to a number of important stressors.

  13. The stress of being chronically ill: from disease-specific to task-specific aspects

    NARCIS (Netherlands)

    Heijmans, M.; Rijken, M.; Foets, M.; Ridder, D.T.D. de; Schreurs, K.; Bensing, J.

    The assumption that disease-related stressors are exclusive for particular diagnoses characterizes many studies of chronically ill patients. In this study the perceptions of 1305 patients from 10 different chronic disease categories were compared with respect to a number of important stressors.

  14. Global stability for infectious disease models that include immigration of infected individuals and delay in the incidence

    Directory of Open Access Journals (Sweden)

    Chelsea Uggenti

    2018-03-01

    Full Text Available We begin with a detailed study of a delayed SI model of disease transmission with immigration into both classes. The incidence function allows for a nonlinear dependence on the infected population, including mass action and saturating incidence as special cases. Due to the immigration of infectives, there is no disease-free equilibrium and hence no basic reproduction number. We show there is a unique endemic equilibrium and that this equilibrium is globally asymptotically stable for all parameter values. The results include vector-style delay and latency-style delay. Next, we show that previous global stability results for an SEI model and an SVI model that include immigration of infectives and non-linear incidence but not delay can be extended to systems with vector-style delay and latency-style delay.

  15. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

    Science.gov (United States)

    Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T; Texier, Yves; van Beersum, Sylvia E C; Horn, Nicola; Willer, Jason R; Mans, Dorus A; Dougherty, Gerard; Lamers, Ideke J C; Coene, Karlien L M; Arts, Heleen H; Betts, Matthew J; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J F; Marcelis, Carlo L; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A; Toedt, Grischa; van Dam, Teunis J P; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L; Blacque, Oliver E; Gibson, Toby J; Huynen, Martijn A; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E; Franco, Brunella; Giles, Rachel H; Ueffing, Marius; Russell, Robert B; Roepman, Ronald

    2016-05-13

    Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.

  16. Cardiorenal metabolic syndrome in the African diaspora: rationale for including chronic kidney disease in the metabolic syndrome definition.

    Science.gov (United States)

    Lea, Janice P; Greene, Eddie L; Nicholas, Susanne B; Agodoa, Lawrence; Norris, Keith C

    2009-01-01

    Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."

  17. Validation of a New Questionnaire with Generic and Disease-Specific Qualities: The Mcgill Copd Quality of Life Questionnaire

    Directory of Open Access Journals (Sweden)

    Smita Pakhale

    2012-01-01

    Full Text Available BACKGROUND: A validated health-related quality of life questionnaire in chronic obstructive pulmonary disease (COPD with advantages of both generic- and disease-specific questionnaires is needed to capture patients’ perspectives of severity and impact of the disease. The McGill COPD questionnaire was created to include these advantages in English and French. It assesses three domains: symptoms, physical function and feelings with 29 items (12 from the 36-item Short-Form Health Survey with 17 from the previously developed COPD-specific module.

  18. Epstein-Barr virus strains and variations: Geographic or disease-specific variants?

    Science.gov (United States)

    Neves, Marco; Marinho-Dias, Joana; Ribeiro, Joana; Sousa, Hugo

    2017-03-01

    The Epstein-Barr Virus (EBV) is associated with the development of several diseases, including infectious mononucleosis (IM), Burkitt's Lymphoma (BL), Nasopharyngeal Carcinoma, and other neoplasias. The publication of EBV genome 1984 led to several studies regarding the identification of different viral strains. Currently, EBV is divided into EBV type 1 (B95-8 strain) and EBV type 2 (AG876 strain), also known as type A and type B, which have been distinguished based upon genetic differences in the Epstein-Barr nuclear antigens (EBNAs) sequence. Several other EBV strains have been described in the past 10 years considering variations on EBV genome, and many have attempted to clarify if these variations are ethnic or geographically correlated, or if they are disease related. Indeed, there is an increasing interest to describe possible specific disease associations, with emphasis on different malignancies. These studies aim to clarify if these variations are ethnic or geographically correlated, or if they are disease related, thus being important to characterize the epidemiologic genetic distribution of EBV strains on our population. Here, we review the current knowledge on the different EBV strains and variants and its association with different diseases. J. Med. Virol. 89:373-387, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Lenferink, Anke; Brusse-Keizer, Marjolein; van der Valk, Paul Dlpm; Frith, Peter A; Zwerink, Marlies; Monninkhof, Evelyn M; van der Palen, Job; Effing, Tanja W

    2017-08-04

    Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease. Exacerbation action plans are considered to be a key component of COPD self-management interventions. Studies assessing these interventions show contradictory results. In this Cochrane Review, we compared the effectiveness of COPD self-management interventions that include action plans for acute exacerbations of COPD (AECOPD) with usual care. To evaluate the efficacy of COPD-specific self-management interventions that include an action plan for exacerbations of COPD compared with usual care in terms of health-related quality of life, respiratory-related hospital admissions and other health outcomes. We searched the Cochrane Airways Group Specialised Register of trials, trials registries, and the reference lists of included studies to May 2016. We included randomised controlled trials evaluating a self-management intervention for people with COPD published since 1995. To be eligible for inclusion, the self-management intervention included a written action plan for AECOPD and an iterative process between participant and healthcare provider(s) in which feedback was provided. We excluded disease management programmes classified as pulmonary rehabilitation or exercise classes offered in a hospital, at a rehabilitation centre, or in a community-based setting to avoid overlap with pulmonary rehabilitation as much as possible. Two review authors independently assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. Study authors were contacted to obtain additional information and missing outcome data where possible. When appropriate, study results were pooled using a random-effects modelling meta-analysis. The primary

  20. Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

    Science.gov (United States)

    Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

    2018-01-01

    Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around

  1. Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

    Science.gov (United States)

    Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

    2018-01-01

    Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD

  2. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

    Directory of Open Access Journals (Sweden)

    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  3. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS.

    Directory of Open Access Journals (Sweden)

    Soo Jin Park

    Full Text Available Central nervous system (CNS inflammatory demyelinating diseases (IDDs are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS, neuromyelitis optica spectrum disorder (NMOSD, and idiopathic transverse myelitis (ITM. Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls. Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.

  4. A validated disease specific prediction equation for resting metabolic rate in underweight patients with COPD

    Directory of Open Access Journals (Sweden)

    Anita Nordenson

    2010-09-01

    Full Text Available Anita Nordenson2, Anne Marie Grönberg1,2, Lena Hulthén1, Sven Larsson2, Frode Slinde11Department of Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden; 2Department of Internal Medicine/Respiratory Medicine and Allergology, Sahlgrenska Academy at University of Gothenburg, SwedenAbstract: Malnutrition is a serious condition in chronic obstructive pulmonary disease (COPD. Successful dietary intervention calls for calculations of resting metabolic rate (RMR. One disease-specific prediction equation for RMR exists based on mainly male patients. To construct a disease-specific equation for RMR based on measurements in underweight or weight-losing women and men with COPD, RMR was measured by indirect calorimetry in 30 women and 11 men with a diagnosis of COPD and body mass index <21 kg/m2. The following variables, possibly influencing RMR were measured: length, weight, middle upper arm circumference, triceps skinfold, body composition by dual energy x-ray absorptiometry and bioelectrical impedance, lung function, and markers of inflammation. Relations between RMR and measured variables were studied using univariate analysis according to Pearson. Gender and variables that were associated with RMR with a P value <0.15 were included in a forward multiple regression analysis. The best-fit multiple regression equation included only fat-free mass (FFM: RMR (kJ/day = 1856 + 76.0 FFM (kg. To conclude, FFM is the dominating factor influencing RMR. The developed equation can be used for prediction of RMR in underweight COPD patients.Keywords: pulmonary disease, chronic obstructive, basal metabolic rate, malnutrition, body composition

  5. Pulmonary granulomatous diseases and pulmonary manifestations of systemic granulomatous disease. Including tuberculosis and nontuberculous mycobacteriosis; Pulmonale granulomatoese Erkrankungen und pulmonale Manifestationen systemischer Granulomatosen. Inklusive Tuberkulose und nichttuberkuloese Mykobakteriosen

    Energy Technology Data Exchange (ETDEWEB)

    Piel, S. [Universitaet Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Heidelberg (Germany); Kreuter, M.; Herth, F. [Universitaet Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kauczor, H.U. [Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Heussel, C.P. [Universitaet Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Thoraxklinik, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany)

    2016-10-15

    Granulomas as signs of specific inflammation of the lungs are found in various diseases with pulmonary manifestations and represent an important imaging finding. The standard imaging modality for the work-up of granulomatous diseases of the lungs is most often thin-slice computed tomography (CT). There are a few instances, e. g. tuberculosis, sarcoidosis and silicosis, where a chest radiograph still plays an important role. Further radiological modalities are usually not needed in the routine work-up of granulomatous diseases of the chest. In special cases magnetic resonance imaging (MRI) and positron emission tomography (PET)-CT scans play an important role, e. g. detecting cardiac sarcoidosis by cardiac MRI or choline C-11 PET-CT in diagnosing lung carcinoma in scar tissue after tuberculosis. The accuracy of thin-slice CT is very high for granulomatous diseases. In cases of chronic disease and fibrotic interstitial lung disease it is important to perform thin-slice CT in order to diagnose a specific disease pattern. Thin-slice CT is also highly sensitive in detecting disease complications and comorbidities, such as malignancies. Given these indications thin-slice CT is generally accepted in the routine daily practice. A thin-slice CT and an interdisciplinary discussion are recommended in many cases with a suspected diagnosis of pulmonary granulomatous disease due to clinical or radiographic findings. (orig.) [German] Granulome als Zeichen der spezifischen Entzuendung im Lungengewebe treten bei zahlreichen Erkrankungen mit pulmonaler Manifestation auf und stellen einen wichtigen Befund in der Bildgebung dar. Das radiologische Standardverfahren bei pulmonalen Granulomatosen ist meistens die Duennschichtcomputertomographie, in wenigen Faellen, wie z. B. bei Tuberkulose, Sarkoidose und Silikose, spielt die Roentgenthoraxuebersicht immer noch eine wichtige Rolle. Bei der Standardabklaerung der meisten Granulomatosen ist die Hinzunahme weiterer Verfahren nicht

  6. Mushroom Lectins: Specificity, Structure and Bioactivity Relevant to Human Disease

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Abol Hassan

    2015-04-01

    Full Text Available Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of mushroom species are known and have been taxonomically classified, mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date summary on the biochemical, molecular and structural properties of mushroom lectins, as well as their versatile applications specifically focusing on mushroom lectin bioactivity.

  7. Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers.

    Science.gov (United States)

    Lewis, James S; Scantlebury, Juliette B; Luo, Jingqin; Thorstad, Wade L

    2012-07-01

    Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (Panaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (Panaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.

  8. Combined scintigraphic and radiographic diagnosis of bone and joint diseases. Including gamma correction interpretation. 4. rev. and enl. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Yong-Whee [Sung Ae General Hospital, Seoul (Korea, Republic of). Dept. of Nuclear Medicine and Radiology

    2013-07-01

    In this fourth edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases, the text has been thoroughly amended, updated, and partially rearranged to reflect the latest advances. In addition to discussing the role of pinhole imaging in the range of disorders previously covered, the new edition pays detailed attention to the novel diagnostic use of gamma correction pinhole bone scan in a broad spectrum of skeletal disorders, including physical, traumatic, and sports injuries, infectious and non-infectious bone diseases, benign and malignant bone tumors, and soft tissue diseases. A large number of state of the art pinhole scans and corroborative CT, MRI, and/or ultrasound images are presented side by side. The book has been enlarged to encompass various new topics, including occult fractures; cervical sprain and whiplash trauma; bone marrow edema; microfractures of trabeculae; evident, gaping, and stress fractures; and differential diagnosis. This new edition will be essential reading for practitioners and researchers in not only nuclear medicine but also radiology, orthopedic surgery, and pathology.

  9. Combined scintigraphic and radiographic diagnosis of bone and joint diseases. Including gamma correction interpretation. 4. rev. and enl. ed.

    International Nuclear Information System (INIS)

    Bahk, Yong-Whee

    2013-01-01

    In this fourth edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases, the text has been thoroughly amended, updated, and partially rearranged to reflect the latest advances. In addition to discussing the role of pinhole imaging in the range of disorders previously covered, the new edition pays detailed attention to the novel diagnostic use of gamma correction pinhole bone scan in a broad spectrum of skeletal disorders, including physical, traumatic, and sports injuries, infectious and non-infectious bone diseases, benign and malignant bone tumors, and soft tissue diseases. A large number of state of the art pinhole scans and corroborative CT, MRI, and/or ultrasound images are presented side by side. The book has been enlarged to encompass various new topics, including occult fractures; cervical sprain and whiplash trauma; bone marrow edema; microfractures of trabeculae; evident, gaping, and stress fractures; and differential diagnosis. This new edition will be essential reading for practitioners and researchers in not only nuclear medicine but also radiology, orthopedic surgery, and pathology.

  10. Non-specific Inflammatory Disease Showed Abnormal FDG Uptake in Lower Extremities

    International Nuclear Information System (INIS)

    Chun, Kyung Ah; Kong, Eun Jung; Cho, Ihn Ho; Hong, Young Hoon; Lee, Choong Ki

    2008-01-01

    Including malignancy, various disease can show abnormal uptake in bone marrow. 1,2) We report a case of non-specific inflammatory FDG uptake in bone marrow mimicking malignancy. A 35-year old woman with fever of unknown origin (FUO) underwent 18 F-FDG PET/CT to find out fever focus and unknown malignancy. 18 F-FDG was injected and imaged 1hr after injection with Discovery ST (GE, USA). 18 F-FDG PET/CT whole body image showed abnormal uptake in lower extremities. MRI and biopsy was also done in the sites of abnormal uptake. PET and MRI suspect malignancy, but biopsy result was non-specific inflammatory process. The patient was improved her clinical condition after antibiotics therapy

  11. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature.

    Science.gov (United States)

    Haberman, Yael; Tickle, Timothy L; Dexheimer, Phillip J; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N; Noe, Joshua D; Rosh, Joel; Markowitz, James; Heyman, Melvin B; Griffiths, Anne M; Crandall, Wallace V; Mack, David R; Baker, Susan S; Huttenhower, Curtis; Keljo, David J; Hyams, Jeffrey S; Kugathasan, Subra; Walters, Thomas D; Aronow, Bruce; Xavier, Ramnik J; Gevers, Dirk; Denson, Lee A

    2014-08-01

    Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

  12. Profiles of microbial fatty acids in the human metabolome are disease-specific

    Directory of Open Access Journals (Sweden)

    Zhanna A Ktsoyan

    2011-01-01

    Full Text Available The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host-microbe co-evolution and co-adaptation. This tight integration creates intense crosstalk and signalling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication. Consequently, the composition of the human metabolome, which includes the gut metabolome, may be different in health and disease states in terms of microbial products and metabolites entering systemic circulation. To test this hypothesis, we measured the level of hydroxy, branched, cyclopropyl and unsaturated fatty acids, aldehydes, and phenyl derivatives in blood of patients with a hereditary autoinflammatory disorder, familial Mediterranean fever (FMF, and in patients with peptic ulceration (PU resulting from Helicobacter pylori infection. Discriminant function analysis of a data matrix consisting of 94 cases as statistical units (37 FMF patients, 14 PU patients, and 43 healthy controls and the concentration of 35 microbial products in the blood as statistical variables revealed a high accuracy of the proposed model (all cases were correctly classified. This suggests that the profile of microbial products and metabolites in the human metabolome is specific for a given disease and may potentially serve as a biomarker for disease.

  13. [Geographical differences in clinical characteristics and management of stable outpatients with coronary artery disease: comparison between the Italian and international population included in the Worldwide CLARIFY registry].

    Science.gov (United States)

    Pozzoli, Massimo; Tavazzi, Luigi

    2014-04-01

    Limited data are available regarding specific differences among countries in demographic and clinical characteristics and treatment of patients with stable coronary artery disease. CLARIFY is an international, prospective and longitudinal registry including more than 33 000 patients with stable coronary artery disease enrolled in 45 countries worldwide. Data were used to compare the characteristics of patients enrolled in Italy with those enrolled in Europe and in the rest of the world. Baseline data were available for 33 283 patients, 2112 of whom from Italy and 12 614 from the remaining western European countries. Italian patients were found to be older, more frequently smoker, hypertensive and with sedentary habits. In addition, they presented more frequently a history of myocardial infarction, carotid arterial disease and chronic obstructive pulmonary disease. In addition, when compared with patients of both European and international cohorts, more Italian patients had undergone coronary angiography and angioplasty. As far as treatment was concerned, a greater number of Italian patients were taking ivabradine, angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, nitrates, thienopyridines, while those taking beta-blockers, calcium antagonists and other antianginal medications were fewer. Among ambulatory patients with stable coronary artery disease, there are important geographic differences in terms of risk factors, clinical characteristics, surgical and pharmacological treatment.

  14. CDDUX: A disease-specific health-related quality-of-life questionnaire for children with celiac disease

    NARCIS (Netherlands)

    van Doorn, Roesja K.; Winkler, Lex M. F.; Zwinderman, Koos H.; Mearin, M. Luisa; Koopman, Hendrik M.

    2008-01-01

    Objective: The development of a disease-specific, health-related, quality-of-life questionnaire for children ages 8 to 18 with celiac disease (CD), together with a parent-as-proxy version. Materials and Methods: We used a focus-group method (bottom-up approach) to investigate the impact of CD on

  15. Quality of life in paediatric inflammatory bowel disease measured by a generic and a disease-specific questionnaire

    NARCIS (Netherlands)

    Loonen, H. J.; Grootenhuis, M. A.; Last, B. F.; Koopman, H. M.; Derkx, H. H. F.

    2002-01-01

    This study assessed the impact of inflammatory bowel disease (IBD) on the health-related quality of life (HRQoL) of children and adolescents. using both a generic and a disease-specific instrument. Three questionnaires were sent to all patients (8-18 y old) from the database of two large

  16. Socioeconomic inequalities in cause-specific mortality after disability retirement due to different diseases.

    Science.gov (United States)

    Polvinen, A; Laaksonen, M; Gould, R; Lahelma, E; Leinonen, T; Martikainen, P

    2015-03-01

    Socioeconomic inequalities in both disability retirement and mortality are large. The aim of this study was to examine socioeconomic differences in cause-specific mortality after disability retirement due to different diseases. We used administrative register data from various sources linked together by Statistics Finland and included an 11% sample of the Finnish population between the years 1987 and 2007. The data also include an 80% oversample of the deceased during the follow-up. The study included men and women aged 30-64 years at baseline and those who turned 30 during the follow-up. We used Cox regression analysis to examine socioeconomic differences in mortality after disability retirement. Socioeconomic differences in mortality after disability retirement were smaller than in the population in general. However, manual workers had a higher risk of mortality than upper non-manual employees after disability retirement due to mental disorders and cardiovascular diseases, and among men also diseases of the nervous system. After all-cause disability retirement, manual workers ran a higher risk of cardiovascular and alcohol-related death. However, among men who retired due to mental disorders or cardiovascular diseases, differences in social class were found for all causes of death examined. For women, an opposite socioeconomic gradient in mortality after disability retirement from neoplasms was found. Conclusions: The disability retirement process leads to smaller socioeconomic differences in mortality compared with those generally found in the population. This suggests that the disability retirement system is likely to accurately identify chronic health problems with regard to socioeconomic status. © 2014 the Nordic Societies of Public Health.

  17. Changes in endocrine thymus function in patients with breast cancer under the action of combined treatment including non-specific active immunotherapy

    International Nuclear Information System (INIS)

    Bendyug, G.D.

    1988-01-01

    The state of endocrine thymus function in patients with breast cancer of the 1st-4th stage and in 31 patients with precancerous diseases is studied. It is established that considerable decrease of thymus serous factor (TSF) content in all patients is observed. Radiation- and polychemotherapy carried out decreases the endocrine thymus function. Inclusions of non-specific active immunotherapy in patients' treatment promote the increase of TSF content, that increases treatment efficiency

  18. Effect of changes in human ecology and behavior on patterns of sexually transmitted diseases, including human immunodeficiency virus infection.

    Science.gov (United States)

    Wasserheit, J N

    1994-01-01

    The last 20 years have witnessed six striking changes in patterns of sexually transmitted diseases (STDs): emergence of new STD organisms and etiologies, reemergence of old STDs, shifts in the populations in which STDs are concentrated, shifts in the etiological spectra of STD syndromes, alterations in the incidence of STD complications, and increases in antimicrobial resistance. For example, human immunodeficiency virus (HIV) emerged to devastate the United States with a fatal pandemic involving at least 1 million people. The incidence of syphilis rose progressively after 1956 to reach a 40-year peak by 1990. In both cases, disease patterns shifted from homosexual men to include minority heterosexuals. Over the last decade, gonorrhea became increasingly concentrated among adolescents, and several new types of antimicrobial resistance appeared. Three interrelated types of environments affect STD patterns. The microbiologic, hormonal, and immunologic microenvironments most directly influence susceptibility, infectiousness, and development of sequelae. These microenvironments are shaped, in part, by the personal environments created by an individual's sexual, substance-use, and health-related behaviors. The personal environments are also important determinants of acquisition of infection and development of sequelae but, in addition, they mediate risk of exposure to infection. These are, therefore, the environments that most directly affect changing disease patterns. Finally, individuals' personal environments are, in turn, molded by powerful macroenvironmental forces, including socioeconomic, demographic, geographic, political, epidemiologic, and technological factors. Over the past 20 years, the profound changes that have occurred in many aspects of the personal environment and the macroenvironment have been reflected in new STD patterns. PMID:8146135

  19. Specificity of anti-tau antibodies when analyzing mice models of Alzheimer's disease: problems and solutions.

    Directory of Open Access Journals (Sweden)

    Franck R Petry

    Full Text Available Aggregates of hyperphosphorylated tau protein are found in a group of diseases called tauopathies, which includes Alzheimer's disease. The causes and consequences of tau hyperphosphorylation are routinely investigated in laboratory animals. Mice are the models of choice as they are easily amenable to transgenic technology; consequently, their tau phosphorylation levels are frequently monitored by Western blotting using a panel of monoclonal/polyclonal anti-tau antibodies. Given that mouse secondary antibodies can recognize endogenous mouse immunoglobulins (Igs and the possible lack of specificity with some polyclonal antibodies, non-specific signals are commonly observed. Here, we characterized the profiles of commonly used anti-tau antibodies in four different mouse models: non-transgenic mice, tau knock-out (TKO mice, 3xTg-AD mice, and hypothermic mice, the latter a positive control for tau hyperphosphorylation. We identified 3 tau monoclonal antibody categories: type 1, characterized by high non-specificity (AT8, AT180, MC1, MC6, TG-3, type 2, demonstrating low non-specificity (AT270, CP13, CP27, Tau12, TG5, and type 3, with no non-specific signal (DA9, PHF-1, Tau1, Tau46. For polyclonal anti-tau antibodies, some displayed non-specificity (pS262, pS409 while others did not (pS199, pT205, pS396, pS404, pS422, A0024. With monoclonal antibodies, most of the interfering signal was due to endogenous Igs and could be eliminated by different techniques: i using secondary antibodies designed to bind only non-denatured Igs, ii preparation of a heat-stable fraction, iii clearing Igs from the homogenates, and iv using secondary antibodies that only bind the light chain of Igs. All of these techniques removed the non-specific signal; however, the first and the last methods were easier and more reliable. Overall, our study demonstrates a high risk of artefactual signal when performing Western blotting with routinely used anti-tau antibodies, and proposes

  20. Longitudinal patterns of predominant asthma disease activity in pediatric patients enrolled in an asthma-specific disease management program.

    Science.gov (United States)

    Scott, Lyne; Nichols, Breck; Choi Kwong, Kenny Yat; Morphew, Tricia; Jones, Craig A

    2008-08-01

    To determine if patterns of predominant asthma disease activity are more closely related than baseline asthma severity to measures of morbidity (acute asthma attack, emergency room visit/hospitalization, missed school days, and/or steroid burst). Retrospective analysis was performed for inner-city Los Angeles asthmatic children (3 to 18 years of age) during their first year of enrollment in an asthma-specific disease management program. All measures of morbidity were more closely related to patterns of predominant disease activity than baseline severity. We conclude that patterns of predominant disease activity are a more significant predictor of asthma morbidity than is baseline severity.

  1. Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

    DEFF Research Database (Denmark)

    Dydensborg Sander, Stine; Størdal, Ketil; Plato Hansen, Tine

    2016-01-01

    PURPOSE: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease......-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records. PATIENTS AND METHODS: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports...... on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes. RESULTS: We identified 2,247 children who were...

  2. Associations of specific psychiatric disorders with isolated focal dystonia, and monogenic and idiopathic Parkinson's disease.

    Science.gov (United States)

    Steinlechner, Susanne; Hagenah, Johann; Rumpf, Hans-Jürgen; Meyer, Christian; John, Ulrich; Bäumer, Tobias; Brüggemann, Norbert; Kasten, Meike; Münchau, Alexander; Klein, Christine; Lencer, Rebekka

    2017-06-01

    Comorbidity of psychiatric disorders in patients with movement disorders is common. Often, psychiatric symptoms manifest before the onset of the movement disorder, thus not representing a mere reaction to its burden. How the disease mechanisms of psychiatric and movement disorders are related is still poorly understood. The aim of the present study was to compare prevalence rates of specific psychiatric disorders between different movement disorders including isolated focal dystonia (IFD, N = 91), monogenic Parkinson's disease (PD, N = 41), idiopathic PD (N = 45), and a sample from a Northern Germany general population (TACOS Study; N = 4075). Our results indicate an odds ratio (OR) of 2.6 [confidence interval (CI) 1.7-4.0] for general axis I disorders in IFD, an OR of 2.5 (CI 1.4-4.7) in monogenic PD, and an OR of 1.4 (CI 0.8-2.6) in idiopathic PD. More specifically, the monogenic PD group showed the highest ORs for affective disorders including depression (OR = 4.9), bipolar disorder (OR = 17.4), and hypomanic episodes (OR = 17.0), whereas IFD expressed the highest rates of anxiety disorders (OR = 3.3). Psychotic symptoms were only observed in the PD groups but not in IFD. Our findings underline the notion that psychiatric disorders are part of the phenotypic spectrum of movement disorders. Moreover, they suggest that IFD, monogenic PD, and idiopathic PD are associated with specific psychiatric disorders indicating disturbances in a different neural circuitry for sensorimotor control.

  3. Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy

    Institute of Scientific and Technical Information of China (English)

    Zhi-Bo Wang; Xiaoqing Zhang; Xue-Jun Li

    2013-01-01

    Establishing human cell models of spinal muscular atrophy (SMA) to mimic motor neuron-specific phenotypes holds the key to understanding the pathogenesis of this devastating disease.Here,we developed a closely representative cell model of SMA by knocking down the disease-determining gene,survival motor neuron (SMN),in human embryonic stem cells (hESCs).Our study with this cell model demonstrated that knocking down of SMN does not interfere with neural induction or the initial specification of spinal motor neurons.Notably,the axonal outgrowth of spinal motor neurons was significantly impaired and these disease-mimicking neurons subsequently degenerated.Furthermore,these disease phenotypes were caused by SMN-full length (SMN-FL) but not SMN-A7 (lacking exon 7)knockdown,and were specific to spinal motor neurons.Restoring the expression of SMN-FL completely ameliorated all of the disease phenotypes,including specific axonal defects and motor neuron loss.Finally,knockdown of SMNFL led to excessive mitochondrial oxidative stress in human motor neuron progenitors.The involvement of oxidative stress in the degeneration of spinal motor neurons in the SMA cell model was further confirmed by the administration of N-acetylcysteine,a potent antioxidant,which prevented disease-related apoptosis and subsequent motor neuron death.Thus,we report here the successful establishment of an hESC-based SMA model,which exhibits disease gene isoform specificity,cell type specificity,and phenotype reversibility.Our model provides a unique paradigm for studying how motor neurons specifically degenerate and highlights the potential importance of antioxidants for the treatment of SMA.

  4. Prospective assessment of disease-specific quality of life in adults with eosinophilic esophagitis.

    Science.gov (United States)

    Stern, E; Taft, T; Zalewski, A; Gonsalves, N; Hirano, I

    2017-10-27

    Eosinophilic esophagitis (EoE) is an important cause of upper gastrointestinal dysfunction in children and adults. The EoE-quality of life (QOL)-A was validated as a disease-specific measure of quality of life in EoE. This study characterized the extent of QOL concerns in a cohort of adult EoE patients and delineated the relationships between QOL and other disease activity measures. One hundred sixty-seven patients enrolled in this prospective cohort study. Patients with established and suspected EoE undergoing endoscopy at a single university-based medical center were recruited. EoE was diagnosed on the basis of the clinical criteria and histologic demonstration of ≥15 eos/hpf while on proton pump inhibition therapy. Sixty five patients undergoing repeat endoscopy during the enrollment period participated twice. Patients provided demographic information and completed symptom assessments and the EoE-QOL-A. Analyses included comparisons with overall QOL as well as QOL subscales. Outcome measures included endoscopic activity using a validated instrument, the EoE Endoscopic Reference Score, and histology. Overall QOL was significantly correlated with dysphagia frequency, intensity, and severity (P food impaction in the last 30 days had significantly worse overall QOL (P = 0.009). There was no correlation between overall QOL and years since diagnosis, symptom duration, endoscopic features, or histologic findings. Patient symptoms correlated with endoscopic features of edema, rings, and stricture severity. Histologic activity was highly correlated with severity of endoscopic features. Patients who underwent repeat endoscopy with histologic response demonstrated improved eating and social QOL; however, overall QOL was unchanged. In adults with EoE, patient reported QOL is associated with symptom severity but not endoscopic or histologic features. Disease-specific QOL may complement parameters of biologic activity in the assessment of overall disease burden in EoE.

  5. Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Koji Hase

    Full Text Available Activation-induced cytidine deaminase (AID expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM and class switch recombination (CSR. Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2 associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.

  6. Disease-specific direct-to-consumer advertising for reminding consumers to take medications.

    Science.gov (United States)

    Bhutada, Nilesh S; Rollins, Brent L

    2015-01-01

    To assess the relationship between disease-specific direct-to-consumer (DTC) advertising, via traditional advertising effectiveness measures, and consumers' self-reported medication-taking behavior. Data were gathered for 514 respondents (age 18 and above) using an online survey panel. Participants were exposed to a disease-specific (i.e., nonbranded) DTC advertising for depression. The advertising stimulus created for the study was based on the Food and Drug Administration guidelines for disease-specific DTC advertising and modeled after current print disease-specific DTC advertising. Participants reviewed the advertising stimulus through the online program and then responded to a questionnaire containing closed-ended questions assessing the constructs. Data were analyzed using chi-square tests. All tests were interpreted at an a priori alpha of 0.05. Significantly more respondents who were highly involved, paid more attention to the advertisement, and were responsive to DTC advertisements in the past indicated that the disease-specific DTC advertising stimulus reminded them to take their depression and other medications. These exploratory results show disease-specific DTC advertising can help people remember to take their prescription medication when viewed, which may lead to more positive medication-taking behavior and increased medication adherence. Additionally, given the fair balance and legal issues surrounding product-specific DTC advertising, disease-specific DTC advertising can serve as an effective component of the marketing mix for pharmaceutical manufacturers. Future research should attempt to study the impact of disease-specific DTC advertising on consumers' actual medication adherence using standardized adherence measures such as prescription records.

  7. Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

    Directory of Open Access Journals (Sweden)

    Denis Bernardi Bichuetti

    2013-05-01

    Full Text Available Although neuromyelitis optica (NMO is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS, few studies comparing both conditions in a single center have been done. Methods: Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007. Results: Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062 with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013 and progression index (0.9 versus 0.6, p≪0.0001, with more patients reaching expanded disability status scale (EDSS 6.0 (39 versus 17%, p=0.0036. The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15. Conclusion: Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

  8. Model Selection and Evaluation Based on Emerging Infectious Disease Data Sets including A/H1N1 and Ebola

    Directory of Open Access Journals (Sweden)

    Wendi Liu

    2015-01-01

    Full Text Available The aim of the present study is to apply simple ODE models in the area of modeling the spread of emerging infectious diseases and show the importance of model selection in estimating parameters, the basic reproduction number, turning point, and final size. To quantify the plausibility of each model, given the data and the set of four models including Logistic, Gompertz, Rosenzweg, and Richards models, the Bayes factors are calculated and the precise estimates of the best fitted model parameters and key epidemic characteristics have been obtained. In particular, for Ebola the basic reproduction numbers are 1.3522 (95% CI (1.3506, 1.3537, 1.2101 (95% CI (1.2084, 1.2119, 3.0234 (95% CI (2.6063, 3.4881, and 1.9018 (95% CI (1.8565, 1.9478, the turning points are November 7,November 17, October 2, and November 3, 2014, and the final sizes until December 2015 are 25794 (95% CI (25630, 25958, 3916 (95% CI (3865, 3967, 9886 (95% CI (9740, 10031, and 12633 (95% CI (12515, 12750 for West Africa, Guinea, Liberia, and Sierra Leone, respectively. The main results confirm that model selection is crucial in evaluating and predicting the important quantities describing the emerging infectious diseases, and arbitrarily picking a model without any consideration of alternatives is problematic.

  9. Multisystem Disease, Including Eosinophilia and Progressive Hyper-Creatine-Kinase-emia over 10 Years, Suggests Mitochondrial Disorder

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2017-04-01

    Full Text Available Background: Eosinophilia has not been reported as a manifestation of a mitochondrial disorder (MID. Here, we report a patient with clinical features suggesting a MID and permanent eosinophilia, multisystem disease, and progressive hyper-creatine-kinase (CK-emia for at least 10 years. Materials and Methods: Methods applied included a clinical exam, blood chemical investigations, electrophysiological investigations, imaging, and invasive cardiological investigations. The patient was repeatedly followed up over several years. He required replacement cardiac surgery. Results: In a 57-year-old male, eosinophilia was first detected at the age of 44 years and has remained almost constantly present until today. In addition to eosinophilia, he developed progressive hyper-CK-emia at the age of 47 years. His history was further positive for hepatopathy, hyperlipidemia, hypothyroidism, renal insufficiency, spontaneous Achilles tendon rupture, double vision, exercise intolerance, muscle aching, mild hypoacusis, sensory neuropathy, seizures, and mitral insufficiency/stenosis requiring valve replacement therapy, oral anticoagulation, and pacemaker implantation. Based on the multisystem nature of his abnormalities and permanent hyper-CK-emia, a MID was suspected. Conclusion: Eosinophilia can be associated with a MID with myopathy, possibly as a reaction to myofiber necrosis. If eosinophilia is associated with progressive hyper-CK-emia and multisystem disease, a MID should be suspected.

  10. A non-specific biomarker of disease activity in HIV/AIDS patients ...

    African Journals Online (AJOL)

    Background: A general non-specific marker of disease activity that could alert the clinician and prompt further investiga- tion would be of ... laration of Helsinki, the National Health Act and the ..... CD8+ lymphocytes and neopterin are related to.

  11. Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries. METHODS: The data from 57 Chinese sCJD patients were retrospectively analyzed, including demographic data, clinical manifestations, laboratory examinations, electroencephalograms (EEGs, diffusion-weighted imaging (DWI scans, positron emission tomography (PET scans, and pathological results. RESULT: The disease was pathologically confirmed in 11 patients. 39 cases were diagnosed as probable sCJD, and 7 were possible. Of the total cases, 33 were male, and 24 were female. The onset age ranged from 36 to 75 years (mean: 55.5, median: 57. Disease onset before the age of 60 occurred in 57.9% of patients. The disease duration from onset to death ranged 5-22 months (mean: 11.6, median: 11, and 51.9% of patients died 7 to 12 months after disease onset. The majority of patients presented with sub-acute onset with progressive dementia. 3 of the 9 patients who took 14-3-3 protein analysis had positive results (33.3%. The sensitivity of EEG was 79.6% (43/54. For DWI and PET examinations, the sensitivities were 94% (47/50 and 94.1% (16/17, respectively. In seven patients who did not show typical hyper-intensities on the first DWI examination, abnormalities of hypo-metabolism in the cerebral cortex were clearly detected by PET. In 13 out of the 17 patients, PET detected extra abnormal regions in addition to the hyper-intense areas observed in DWI. CONCLUSION: This is the first study to indicate that Chinese sCJD patients have a much earlier onset age and a longer disease duration than other populations, which is most likely related to racial differences. The longer disease duration may also be a probable characteristic of Asian populations. PET had high sensitivity for the

  12. Sensibility and specificity of the stress echocardiography with Dobutamine for the detection of coronary disease

    International Nuclear Information System (INIS)

    Senior, Juan Manuel; Escobar, Carlos Ignacio; Jaramillo, Mario and others

    2001-01-01

    Dobutamine stress echocardiography has become a useful method for detecting coronary artery disease in the high prevalence population. The reported sensitivity varies between 76-90% and the specificity between 60-95%. 60-95% there have been few reports regarding sensitivity and specificity among our population. The aim of this study was to evaluate the sensitivity of dopamine stress echocardiography in a population with a high probability of coronary disease. This was a randomized retrospective-prospective study. Between February 1 of 1998 and February 1 of 1999. 409 patients underwent dopamine stress echocardiography and were analyzed according to established protocol. The Dobutamine stress echocardiography as well as the angiography was checked in a blind form by one of the participating researchers trained in those procedures. The diagnostic concordance was found to be greater than 90%. Significant coronary disease was considered to be present in those cases in which there was severe stenosis greater than 50% in a major epicardial artery or greater than 40 % in the left main artery. Coronary arteriography was performed within three months of Dobutamine stress echocardiography imaging. A sixteen-segment model was used as the index for the evaluation of systolic wall thickening and the results were classified as follows: normal (l), ischemia (ll), fixed abnormality (lll) and mixed (lV). 409 patients with an average age of 62.8 +/- 12) were included in the study at random. Six patients with mediocre technical examinations were excluded. 47 % were male. 29% had a history of myocardial infarction, 35 % had a history of arterial hypertension and 10% had diabetes mellitus. The average ejection fraction was 54 +/- 13%. The examination was prescribed in order to detect the presence of ischemia in 95.8% of the cases and as part of preoperative evaluation in 4.2 %. There were adverse effects in 40% of the cases; 15% of these were systemic and 25 % cardiac. The test was

  13. 22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

    Science.gov (United States)

    Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

    2017-04-01

    Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH. © 2017 Wiley Periodicals, Inc.

  14. Assessing Disease Class-Specific Diagnostic Ability: A Practical Adaptive Test Approach.

    Science.gov (United States)

    Papa, Frank J.; Schumacker, Randall E.

    Measures of the robustness of disease class-specific diagnostic concepts could play a central role in training programs designed to assure the development of diagnostic competence. In the pilot study, the authors used disease/sign-symptom conditional probability estimates, Monte Carlo procedures, and artificial intelligence (AI) tools to create…

  15. Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination

    DEFF Research Database (Denmark)

    Patch, J.R.; Pedersen, Lasse Eggers; Toka, F.N.

    2011-01-01

    Foot-and-mouth disease (FMD) continues to be a significant threat to the health and economic value of livestock species. This acute infection is caused by the highly contagious FMD virus (FMDV), which infects cloven-hoofed animals including large and small ruminants and swine. Current vaccine...... cytopathic virus. Here, we have used recombinant human adenovirus vectors as a means of delivering FMDV antigens in a T cell-directed vaccine in pigs. We tested the hypothesis that impaired processing of the FMDV capsid would enhance cytolytic activity, presumably by targeting all proteins for degradation...... and effectively increasing the class I MHC/FMDV peptide concentration for stimulation of a CTL response. We compared such a T cell targeting vaccine with the parental vaccine, previously shown to effectively induce a neutralizing antibody response. Our results show induction of FMDV-specific CD8(+) CTL killing...

  16. Including pathogen risk in life cycle assessment of wastewater management. 1. Estimating the burden of disease associated with pathogens.

    Science.gov (United States)

    Harder, Robin; Heimersson, Sara; Svanström, Magdalena; Peters, Gregory M

    2014-08-19

    The environmental performance of wastewater and sewage sludge management is commonly assessed using life cycle assessment (LCA), whereas pathogen risk is evaluated with quantitative microbial risk assessment (QMRA). This study explored the application of QMRA methodology with intent to include pathogen risk in LCA and facilitate a comparison with other potential impacts on human health considered in LCA. Pathogen risk was estimated for a model wastewater treatment system (WWTS) located in an industrialized country and consisting of primary, secondary, and tertiary wastewater treatment, anaerobic sludge digestion, and land application of sewage sludge. The estimation was based on eight previous QMRA studies as well as parameter values taken from the literature. A total pathogen risk (expressed as burden of disease) on the order of 0.2-9 disability-adjusted life years (DALY) per year of operation was estimated for the model WWTS serving 28,600 persons and for the pathogens and exposure pathways included in this study. The comparison of pathogen risk with other potential impacts on human health considered in LCA is detailed in part 2 of this article series.

  17. Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF.

    Science.gov (United States)

    Rotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafà, Roberta; Gaboriaud, Pauline; Touzé, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, Mauro

    2017-07-15

    Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs. Experimental Design: Serum samples from patients with MCC were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins large T (LT) and small T (ST) antigens and the viral capsid protein-1 were analyzed by indirect ELISA. Viral antigens were recombinant LT/ST and virus-like particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein. Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain. PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1 to 30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen-positive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control. Conclusions: We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause-effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity. Clin Cancer Res; 23(14); 3929-34. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Systematic review with meta-analysis: online psychological interventions for mental and physical health outcomes in gastrointestinal disorders including irritable bowel syndrome and inflammatory bowel disease.

    Science.gov (United States)

    Hanlon, I; Hewitt, C; Bell, K; Phillips, A; Mikocka-Walus, A

    2018-06-14

    Online psychotherapy has been successfully used as supportive treatment in many chronic illnesses. However, there is a lack of evidence on its role in the management of gastrointestinal (GI) diseases. To examine whether online psychological interventions improve mental and physical outcomes in gastrointestinal diseases. We searched CINAHL Plus, MEDLINE, EMBASE, Health Management Information Consortium, PsycINFO, British Nursing Index, Cochrane Library, a specialised register of the IBD/FBD Cochrane Group, MEDLINE (PubMed) WHO International Clinical Trial Registry, ClinicalTrials.gov, and reference lists of all papers included in the review. The Cochrane Risk of Bias Tool was used to assess internal validity. Where possible, data were pooled using random-effects meta-analysis. We identified 11 publications (encompassing nine studies) meeting inclusion criteria. One study had a high risk of selection bias (allocation concealment), all studies had a high risk of performance and detection bias. Eight studies were included in the meta-analyses (6 on irritable bowel syndrome [IBS] and two on inflammatory bowel disease [IBD]). Online cognitive behavioural therapy (CBT) was shown to significantly improve gastrointestinal symptom-specific anxiety (MD: -8.51, 95% CI -12.99 to -4.04, P = 0.0002) and lessen symptom-induced disability (MD: -2.78, 95% CI -5.43 to -0.12, P = 0.04) in IBS post intervention. There was no significant effect of online CBT on any other outcomes in IBS. No significant effect of online psychotherapy was demonstrated in IBD. There is insufficient evidence to demonstrate the effectiveness of online CBT to manage mental and physical outcomes in gastrointestinal diseases. © 2018 John Wiley & Sons Ltd.

  19. Muscle-Specific Mis-Splicing and Heart Disease Exemplified by RBM20.

    Science.gov (United States)

    Rexiati, Maimaiti; Sun, Mingming; Guo, Wei

    2018-01-05

    Alternative splicing is an essential post-transcriptional process to generate multiple functional RNAs or proteins from a single transcript. Progress in RNA biology has led to a better understanding of muscle-specific RNA splicing in heart disease. The recent discovery of the muscle-specific splicing factor RNA-binding motif 20 (RBM20) not only provided great insights into the general alternative splicing mechanism but also demonstrated molecular mechanism of how this splicing factor is associated with dilated cardiomyopathy. Here, we review our current knowledge of muscle-specific splicing factors and heart disease, with an emphasis on RBM20 and its targets, RBM20-dependent alternative splicing mechanism, RBM20 disease origin in induced Pluripotent Stem Cells (iPSCs), and RBM20 mutations in dilated cardiomyopathy. In the end, we will discuss the multifunctional role of RBM20 and manipulation of RBM20 as a potential therapeutic target for heart disease.

  20. Disease specific knowledge about cystic fibrosis, patient education and counselling in Poland

    Directory of Open Access Journals (Sweden)

    Sławomir Chomik

    2014-06-01

    Full Text Available introduction and objective. The presented study assesses levels of specific knowledge of the disease among cystic fibrosis (CF patients and their families, and evaluates the effectiveness of a targeted, disease specific education programme. materials and methods. A cross-sectional survey among 462 families with a CF child evaluated their knowledge of the disease. A one year follow up survey among 200 families assessed the effectiveness of an educational programme developed to correct gaps, errors and misconceptions identified in the previously administered survey. Self-administered, comprehensive, 5-domains, 45-item multiple-choice CF Disease Knowledge Questionnaire (CFDKQ was anonymously completed by 462 subjects. results. 228 respondents were male (49%, 234 female (51%. The level of disease-specific knowledge in the age groups 0–6 and 7–10 years, was significantly higher than in 11–14 and 15–18 years of age groups (p<0.005. General medical and Genetics/Reproduction knowledge was low in all patients. Significant predictors of patient and parental knowledge were age and domicile. Patients and parents rely heavily on doctors for information about CF (77%. The follow-up survey (CFDKQ emphasized that special education programmes significantly improved levels of disease specific knowledge (p<0.0001. conclusions. If left uncorrected, the misconceptions, gaps and errors in CF knowledge identified in the presented study could result in inadvertent non-adherence to treatment, and impact on the progression and outcome of the disease. Secondly, the results demonstrate the effectiveness of targeted, disease specific information in improving disease knowledge of CF patients and their families, and highlights the value and need for the development of educational programmes for chronically ill patients and their families.

  1. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  2. Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

    Science.gov (United States)

    Taylor, Kimberly E.; Remmers, Elaine F.; Lee, Annette T.; Ortmann, Ward A.; Plenge, Robert M.; Tian, Chao; Chung, Sharon A.; Nititham, Joanne; Hom, Geoffrey; Kao, Amy H.; Demirci, F. Yesim; Kamboh, M. Ilyas; Petri, Michelle; Manzi, Susan; Kastner, Daniel L.; Seldin, Michael F.; Gregersen, Peter K.; Behrens, Timothy W.; Criswell, Lindsey A.

    2008-01-01

    Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2 = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10−16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10−19), nephritis (MAF = 34.3%, OR = 1.80, p<10−11), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10−13). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10−4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease. PMID

  3. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Kimberly E Taylor

    2008-05-01

    Full Text Available Systemic lupus erythematosus (SLE is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398 and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r(2 = 0.94 to 0.99 were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10(-16. This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19, nephritis (MAF = 34.3%, OR = 1.80, p<10(-11, and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13. An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10(-4 in the homogeneous subset of subjects. In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease.

  4. Tissue-specific functional networks for prioritizing phenotype and disease genes.

    Directory of Open Access Journals (Sweden)

    Yuanfang Guan

    Full Text Available Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

  5. Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

    Science.gov (United States)

    Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

    2010-12-14

    The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.

  6. Specificity and sensibility of 9-Itens Wearing-off Questionnaire in Brazilian Parkinson disease patient sample

    Directory of Open Access Journals (Sweden)

    Jasper Guimarães Santos

    2014-11-01

    Full Text Available Objective (1 To evaluate whether the Nine Items Questionnaire (WOQ-9 for the detection of wearing-off (WO in Parkinson Disease (PD, by means of its screening ability, is a helpful tool to assist neurologists in diagnosing WO; (2 To determine the sensitivity and the specificity of a free Brazilian Portuguese translation of WOQ-9. Method A sample obtained by convenience included 60 patients. The WOQ-9 was answered by the patients themselves before their routine consultations. The detection of the WO by the WOQ-9 was compared with the neurologist assessment. Statistical significance was 5%. Results The WOQ-9 showed sensitivity of 100%, specificity of 10.3%, positive and negative predictive values of 54.4% and 100% respectively. The identification of WO by the WOQ-9 was congruent in 54.5% of cases with neurological evaluation. Conclusion The WOQ-9 is a convenient screening tool to aid physicians to detect WO in PD patients, and it is a quick and easy self-administered questionnaire.

  7. Low specificity and sensitivity of smell identification testing for the diagnosis of Parkinson?s disease

    Directory of Open Access Journals (Sweden)

    Mayela Rodríguez-Violante

    Full Text Available Objective: The aim of this study is to determine if the University of Pennsylvania’s Smell Identification Test (UPSIT is an accurate diagnostic tool for olfactory dysfunction in Parkinson’s disease (PD. Method: We included 138 non-demented PD subjects and 175 control subjects matched by gender. Smell identification was tested using UPSIT. Results: The mean number of UPSIT items correctly identified by controls was 27.52±5.88; the mean score for PD subjects was 19.66±6.08 (p=<0.001. UPSIT sensitivity was 79.7% with a specificity of 68.5% using a cut-off score of ≤25. The overall accuracy for the diagnosis of PD was of 75.3%. Conclusion: UPSIT accuracy and specificity were lower than what has been previously reported. Our data demonstrates that 17.5% of items of the UPSIT were not well identified by healthy controls. Further research of the identification of a truly cross-cultural test is warranted.

  8. Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease (Review)

    NARCIS (Netherlands)

    Lenferink, Anke; Brusse-Keizer, Marjolein; van der Valk, Paul; Frith, Peter A.; Zwerink, Marlies; Monninkhof, Evelyn M.; van der Palen, J.A.M.; Effing, Tanja

    2017-01-01

    Background  Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals ofmotivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease.

  9. Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Lenferink, Anke; Brusse-Keizer, Marjolein; van der Valk, Paul D.L.P.M.; Frith, Peter A.; Zwerink, Marlies; Monninkhof, Evelyn M.; van der Palen, Job; Effing-Tijdhof, Tanja W

    2017-01-01

    Background: Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease.

  10. Multiple factors, including non-motor impairments, influence decision making with regard to exercise participation in Parkinson's disease: a qualitative enquiry.

    Science.gov (United States)

    O'Brien, Christine; Clemson, Lindy; Canning, Colleen G

    2016-01-01

    To explore how the meaning of exercise and other factors interact and influence the exercise behaviour of individuals with Parkinson's disease (PD) enrolled in a 6-month minimally supervised exercise program to prevent falls, regardless of whether they completed the prescribed exercise or not. This qualitative study utilised in-depth semi-structured interviews analysed using grounded theory methodology. Four main themes were constructed from the data: adapting to change and loss, the influence of others, making sense of the exercise experience and hope for a more active future. Participation in the PD-specific physiotherapy program involving group exercise provided an opportunity for participants to reframe their identity of their "active" self. Three new influences on exercise participation were identified and explored: non-motor impairments of apathy and fatigue, the belief in a finite energy quota, and the importance of feedback. A model was developed incorporating the themes and influences to explain decision-making for exercise participation in this group. Complex and interacting issues, including non-motor impairments, need to be considered in order to enhance the development and ongoing implementation of effective exercise programmes for people with PD. Exercise participation can assist individuals to reframe their identity as they are faced with losses associated with Parkinson's disease and ageing. Non-motor impairments of apathy and fatigue may influence exercise participation in people with Parkinson's disease. Particular attention needs to be paid to the provision of feedback in exercise programs for people with Parkinson's disease as it important for their decision-making about continuing exercise.

  11. Disease-specific health-related quality of life in patients with esophageal achalasia before and after therapy.

    Science.gov (United States)

    Garrigues, V; Ortiz, V; Casanova, C; Bujanda, L; Moreno-Osset, E; Rodríguez-Téllez, M; Montserrat, A; Brotons, A; Fort, E; Ponce, J

    2010-07-01

    To evaluate disease-specific health-related quality of life (HRQoL) in patients with symptomatic esophageal achalasia before and after therapy. Symptoms and disease-specific HRQoL were evaluated before and 3 months after therapy. Therapy selection, either dilatation or myotomy, depended exclusively on the opinion of the physician on charge of the patient. Symptom severity was graded from 0 to 3, using a scoring system. A disease-specific questionnaire for achalasia developed and validated in Spanish language with 18 items and four subscales (AE-18) was used to evaluate HRQoL. Changes after therapy in HRQoL and its association with clinical improvement were analyzed. Sixty-five patients were prospectively included in eight hospitals in Spain. Of them, 47 were treated with dilatation, and 18 with laparoscopic Heller myotomy. After therapy, AE-18 global and subscales scores improved significantly. Changes in HRQoL were associated with improvement in symptoms. An important improvement in symptoms (>or=50%) was needed to obtain a minimal clinically important improvement (>or=20%) in HRQoL. Disease-specific HRQoL improves in patients with symptomatic achalasia after therapy with dilatation or myotomy. The degree of improvement of HRQoL depends on the degree of improvement of esophageal symptoms.

  12. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients

    Directory of Open Access Journals (Sweden)

    Meng-Lu Liu

    2016-01-01

    Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  13. Exercise thallium-201 myocardial imaging in left main coronary artery disease: sensitive but not specific

    International Nuclear Information System (INIS)

    Rehn, T.; Griffith, L.S.; Achuff, S.C.; Bailey, I.K.; Bulkley, B.H.; Burow, R.; Pitt, B.; Becker, L.C.

    1981-01-01

    To determine the usefulness of thallium-201 scintigraphy for identifying left main coronary artery disease, the results of scintigraphy at rest and during exercise were compared in 24 patients with 50 percent or greater narrowing of the left main coronary artery and 80 patients with 50 percent or greater narrowing of one or more of the major coronary arteries but without left main coronary involvement. By segmental analysis of the scintigrams, perfusion defects were assigned to the left anterior descending, left circumflex or right coronary artery, singly or in combination, and the pattern of simultaneous left anterior descending and circumflex arterial defects was used to identify left main coronary artery disease. Of the 24 patients with left main coronary artery disease, 22 (92 percent) had abnormal exercise scintigrams. Despite this high sensitivity, the pattern of perfusion defects was not specific; the ''left main pattern'' was found in 3 patients (13 percent) with left main coronary artery disease but also in 3 (33 percent) of 9 patients with combined left anterior descending and left circumflex arterial disease, 4 (19 percent) of 21 patients with three vessel disease and 3 (6 percent) of 50 patients with one or two vessel disease but excluding the group with left anterior descending plus left circumflex arterial disease. The pattern of perfusion defects in the patients with left main coronary artery disease was determined by the location and severity of narrowings in the coronary arteries downstream from the left main arterial lesion. Concomitant lesions in other arteries were found in all patients with left main coronary disease (one vessel in 1 patient, two vessels in 7 patients and three vessels in 16). For this reason, it is unlikely that even with improvements in radiopharmaceutical agents and imaging techniques, myocardial perfusion scintigraphy will be sufficiently specific for definitive identification of left main coronary artery disease

  14. Methodological principles of radiation influence upon specific function of female organism and gynecological diseases

    International Nuclear Information System (INIS)

    Tsvelev, Yu.V.; Kira, E.F.

    1994-01-01

    1025 women permanently residing at the territory subjected to radioactive contamination due to the Chernobyl NPP accident underwent dispensary examination in 1991-1992. Study of ionizing radiation influence on specific functions (menstrual, reproductive, secretory and gynecological) of female organism is carried out. It is found that the highest percentage in the structure of gynecological diseases is accounted for inflammatory diseases of uterine appendages and neck of the uterus. 1 tab

  15. Analysis and description of disease-specific quality of life in patients with anal fistula.

    Science.gov (United States)

    Ferrer-Márquez, Manuel; Espínola-Cortés, Natalia; Reina-Duarte, Ángel; Granero-Molina, José; Fernández-Sola, Cayetano; Hernández-Padilla, José Manuel

    2018-04-01

    In patients diagnosed with anal fistula, knowing the quality of life specifically related to the disease can help coloproctology specialists to choose the most appropriate therapeutic strategy for each case. The aim of our study is to analyzse and describe the factors related to the specific quality of life in a consecutive series of patients diagnosed with anal fistula. Observational, cross-sectional study carried out from March 2015 to February 2017. All patients were assessed in the colorectal surgery unit of a hospital in southeast of Spain. After performing an initial anamnesis and a physical examination, patients diagnosed with anal fistula completed the Quality of Life in Ppatients with Anal Fistula Questionnaire (QoLAF-Q). This questionnaire specifically measures quality of life in people with anal fistula and its score range is the following: zero impact = 14 points, limited impact = 15 to 28 points, moderate impact = 29 to 42 points, high impact = 43 to 56 points, and very high impact = 57 to 70 points. A total of 80 patients were included. The median score obtained in the questionnaire for the sample studied was 34.00 (range=14-68). Statistically significant differences between patients with "primary anal fistula" (n=65) and "recurrent anal fistula" (n=15) were observed (mean rank=42.96 vs. mean rank=29.83, p=0.048). Furthermore, an inverse proportion (P=.016) between "time with clinical symptoms" and "impact on quality of life" was found (5 years: mean rank = 19.00). There were no statistically significant differences (P=.149) between quality of life amongst patients diagnosed with complex (mean rank = 36.13) and simple fistulae (mean rank = 43.59). Anal fistulae exert moderate-high impact on patients' quality of life. "Shorter time experiencing clinical symptoms" and the "presence of primary fistula" are factors that can be associated with worse quality of life. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Newly Diagnosed Meniere's Disease: Clinical Course With Initiation of Noninvasive Treatment Including an Accounting of Vestibular Migraine.

    Science.gov (United States)

    Sbeih, Firas; Christov, Florian; Gluth, Michael B

    2018-05-01

    To describe the course of Meniere's disease with noninvasive treatment during the first few years after initial diagnosis. A retrospective review of consecutive patients with newly diagnosed definite Meniere's disease between 2013 and 2016 and a minimum follow-up of 1 year. Patients received a written plan for low sodium, water therapy, and treatment with a diuretic and/or betahistine. Subjects were screened and treated for vestibular migraine as needed. Vertigo control and hearing status at most recent follow-up were assessed. Forty-four subjects had an average follow up of 24.3 months. Thirty-four percent had Meniere's disease and vestibular migraine, and 84% had unilateral Meniere's disease. Seventy-five percent had vertigo well controlled at most recent follow-up, with only noninvasive treatments. Age, gender, body mass index, presence of vestibular migraine, bilateral disease, and duration of follow-up did not predict noninvasive treatment failure. Worse hearing threshold at 250 Hz and lower pure tone average (PTA) at the time of diagnosis did predict failure. Fifty-two percent of ears had improved PTA at most recent visit, 20% had no change, and 28% were worse Conclusions: Encountering excellent vertigo control and stable hearing after a new diagnosis of Meniere's disease is possible with noninvasive treatments. Worse hearing status at diagnosis predicted treatment failure.

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-15

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

  19. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

    Directory of Open Access Journals (Sweden)

    Katerina Markopoulou

    Full Text Available Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L, which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may

  20. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

    Science.gov (United States)

    Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

    2016-01-01

    Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the

  1. The Contribution of Specific Diseases to Educational Disparities in Disability-Free Life Expectancy

    Science.gov (United States)

    Nusselder, Wilma J.; Looman, Caspar W.N.; Mackenbach, Johan P.; Huisman, Martijn; van Oyen, Herman; Deboosere, Patrick; Gadeyne, Sylvie; Kunst, Anton E.

    2005-01-01

    Objectives. We examined the contribution that specific diseases, as causes of both death and disability, make to educational disparities in disability-free life expectancy (DFLE). Methods. We used disability data from the Belgian Health Interview Survey (1997) and mortality data from the National Mortality Follow-Up Study (1991–1996) to assess education-related disparities in DFLE and to partition these differences into additive contributions of specific diseases. Results. The DFLE advantage of higher-educated compared with lower-educated persons was 8.0 years for men and 5.9 years for women. Arthritis (men, 1.3 years; women, 2.2 years), back complaints (men, 2.1 years), heart disease/stroke (men, 1.5 years; women, 1.6 years), asthma/chronic obstructive pulmonary disease (COPD) (men, 1.2 years; women, 1.5 years), and “other diseases” (men, 2.4 years) contributed the most to this difference. Conclusions. Disabling diseases, such as arthritis, back complaints, and asthma/COPD, contribute substantially to differences in DFLE by education. Public health policy aiming to reduce existing disparities in the DFLE and to improve population health should not only focus on fatal diseases but also on these nonfatal diseases. PMID:16195519

  2. Radioimmunoassay for detection of VP1 specific neutralizing antibodies of foot and mouse disease virus

    International Nuclear Information System (INIS)

    Patzer, E.J.; Jackson, M.L.; Moore, D.M.

    1985-01-01

    A solid-phase radioimmunoassay was developed for the detection of antibodies against a specific region of the VP1 protein of the A24 and O1 serotypes of foot and mouth disease virus. The antibody titers from the radioimmunoassay showed a positive correlation with neutralizing antibody titers determined by a mouse protection assay. The specificity of the assay resides in the peptide used as antigen. The assay is rapid, reproducible and does not require the use of whole virions. (orig.)

  3. User's guide for shipping Type B quantities of radioactive and fissile material, including plutonium, in DOT-6M specification packaging configurations

    International Nuclear Information System (INIS)

    Kelly, D.L.

    1994-09-01

    The need for developing a user's guide for shipping Type B quantities of radioactive and fissile material, including plutonium, in a US Department of Transportation Specification 6M (DOT-6M) packaging was identified by the US Department of Energy (DOE)-Headquarters, Transportation Management Division (EM-261) because the DOT-6M packaging is widely used by DOE site contractors and the DOE receives many questions about approved packaging configuration. Currently, EM-261 has the authority to approve new DOT-6M packaging configurations for use by the DOE Operations Offices. This user's guide identifies the DOE-approved DOT-6M packaging configurations and explains how to have new configurations approved by the DOE. The packaging configurations described in this guide are approved by the DOE, and satisfy the applicable DOT requirements and the identified DOE restrictions. These packaging configurations are acceptable for transport of Type B quantities of radioactive and fissile material, including plutonium

  4. Varied autopsy findings in five treated patients with Gaucher disease and parkinsonism include the absence of Gaucher cells.

    Science.gov (United States)

    Monestime, Gianina; Borger, Daniel K; Kim, Jenny; Lopez, Grisel; Allgaeuer, Michael; Jain, Dhanpat; Vortmeyer, Alexander; Wang, Hao-Wei; Sidransky, Ellen

    2016-05-01

    Enzyme replacement therapy is standard of care for patients with Gaucher disease, as it significantly improves skeletal, visceral, and hematological symptoms. Few pathological studies have documented the extent of pathological findings in treated patients. Autopsy findings in five treated patients, who ultimately developed parkinsonism, ranged from the complete absence of Gaucher pathology to extensive involvement of multiple tissues, without correlation to age, genotype, spleen status, or dose/duration of therapy. Additional autopsies may elucidate modifiers and biomarkers contributing to disease burden and response to therapy. Published by Elsevier Inc.

  5. Sequence-specific 1H-NMR assignments for the aromatic region of several biologically active, monomeric insulins including native human insulin.

    Science.gov (United States)

    Roy, M; Lee, R W; Kaarsholm, N C; Thøgersen, H; Brange, J; Dunn, M F

    1990-06-12

    The aromatic region of the 1H-FT-NMR spectrum of the biologically fully-potent, monomeric human insulin mutant, B9 Ser----Asp, B27 Thr----Glu has been investigated in D2O. At 1 to 5 mM concentrations, this mutant insulin is monomeric above pH 7.5. Coupling and amino acid classification of all aromatic signals is established via a combination of homonuclear one- and two-dimensional methods, including COSY, multiple quantum filters, selective spin decoupling and pH titrations. By comparisons with other insulin mutants and with chemically modified native insulins, all resonances in the aromatic region are given sequence-specific assignments without any reliance on the various crystal structures reported for insulin. These comparisons also give the sequence-specific assignments of most of the aromatic resonances of the mutant insulins B16 Tyr----Glu, B27 Thr----Glu and B25 Phe----Asp and the chemically modified species des-(B23-B30) insulin and monoiodo-Tyr A14 insulin. Chemical dispersion of the assigned resonances, ring current perturbations and comparisons at high pH have made possible the assignment of the aromatic resonances of human insulin, and these studies indicate that the major structural features of the human insulin monomer (including those critical to biological function) are also present in the monomeric mutant.

  6. Modeling the Cumulative Effects of Social Exposures on Health: Moving beyond Disease-Specific Models

    Directory of Open Access Journals (Sweden)

    Heather L. White

    2013-03-01

    Full Text Available The traditional explanatory models used in epidemiology are “disease specific”, identifying risk factors for specific health conditions. Yet social exposures lead to a generalized, cumulative health impact which may not be specific to one illness. Disease-specific models may therefore misestimate social factors’ effects on health. Using data from the Canadian Community Health Survey and Canada 2001 Census we construct and compare “disease-specific” and “generalized health impact” (GHI models to gauge the negative health effects of one social exposure: socioeconomic position (SEP. We use logistic and multinomial multilevel modeling with neighbourhood-level material deprivation, individual-level education and household income to compare and contrast the two approaches. In disease-specific models, the social determinants under study were each associated with the health conditions of interest. However, larger effect sizes were apparent when outcomes were modeled as compound health problems (0, 1, 2, or 3+ conditions using the GHI approach. To more accurately estimate social exposures’ impacts on population health, researchers should consider a GHI framework.

  7. Mortality from circulatory diseases by specific country of birth across six European countries: test of concept

    NARCIS (Netherlands)

    Bhopal, Raj S.; Rafnsson, Snorri B.; Agyemang, Charles; Fagot-Campagna, Anne; Giampaoli, Simona; Hammar, Niklas; Harding, Seeromanie; Hedlund, Ebba; Juel, Knud; Mackenbach, Johan P.; Primatesta, Paola; Rey, Gregoire; Rosato, Michael; Wild, Sarah; Kunst, Anton E.

    2012-01-01

    Background: Important differences in cardiovascular disease (CVD) mortality by country of birth have been shown within European countries. We now focus on CVD mortality by specific country of birth across European countries. Methods: For Denmark, England and Wales, France, The Netherlands, Scotland

  8. Disease-specific and inflammation-independent stromal alterations in spondylarthritis synovitis

    NARCIS (Netherlands)

    Yeremenko, Nataliya; Noordenbos, Troy; Cantaert, Tineke; van Tok, Melissa; van de Sande, Marleen; Cañete, Juan D.; Tak, Paul P.; Baeten, Dominique

    2013-01-01

    The molecular processes driving the distinct patterns of synovial inflammation and tissue remodeling in spondylarthritis (SpA) as compared to rheumatoid arthritis (RA) remain largely unknown. Therefore, we aimed to identify novel and unsuspected disease-specific pathways in SpA by a systematic and

  9. Effect of pneumococcal conjugate vaccination on serotype-specific carriage and invasive disease in England: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Stefan Flasche

    2011-04-01

    Full Text Available BACKGROUND: We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7 programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. METHODS AND FINDINGS: Nasopharyngeal swabs were taken from children <5 y old and family members (n=400 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49. The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. CONCLUSION: Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.

  10. Current roles of specific bacteria in the pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Lucy McMullen

    2015-12-01

    Full Text Available The relevance of alterations in gut microbiota in the pathogenesis of inflammatory bowel disease (IBD remains unclear. Currently there is conflicting evidence with regards to the roles of specific bacterial species. Escherichia coli (particularly the adherent invasive strain are more prevalent in those with IBD and are associated with higher risk of IBD. However, the organisms are also present in healthy individuals and colonisation does not correlate with the degree of inflammation in IBD. Campylobacter concisus is more prevalent in those with IBD and higher levels of C. concisus specific IgG antibodies are found in the serum of those with IBD compared to healthy controls. Further, C. concisus has immunogenic properties that stimulate an antibody response suggesting the bacteria might trigger or exacerbate disease. Conversely most mycobacteria are unlikely to be causative as they are not presentin microbial stool cultures early in disease. In various studies,Mycobacterium aviumparatuberculosishas been detected both more frequently and not at all in individuals with Crohn's disease. Similar conflict exists with respect to Yersinia enterocolitica,Bacteroidesvulgatus and Helicobacter hepaticus, which are also more prevalent in IBD. However, these organisms appear more likely to contribute to disease persistence than initial disease development. This review aims to summarise the current understanding of key bacterial species implicated in the pathogenesis of IBD.

  11. Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response

    Science.gov (United States)

    2014-01-01

    While the antigenic specificity and pathogenic relevance of immunologic reactivity to gluten in celiac disease have been extensively researched, the immune response to nongluten proteins of wheat has not been characterized. We aimed to investigate the level and molecular specificity of antibody response to wheat nongluten proteins in celiac disease. Serum samples from patients and controls were screened for IgG and IgA antibody reactivity to a nongluten protein extract from the wheat cultivar Triticum aestivum Butte 86. Antibodies were further analyzed for reactivity to specific nongluten proteins by two-dimensional gel electrophoresis and immunoblotting. Immunoreactive molecules were identified by tandem mass spectrometry. Compared with healthy controls, patients exhibited significantly higher levels of antibody reactivity to nongluten proteins. The main immunoreactive nongluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins. Assessment of reactivity toward purified recombinant proteins further confirmed the presence of antibody response to specific antigens. The results demonstrate that, in addition to the well-recognized immune reaction to gluten, celiac disease is associated with a robust humoral response directed at a specific subset of the nongluten proteins of wheat. PMID:25329597

  12. Gastroesophageal Reflux Disease and overall and Cause-specific Mortality: A Prospective Study of 50000 Individuals

    Science.gov (United States)

    Islami, Farhad; Pourshams, Akram; Nasseri-Moghaddam, Siavosh; Khademi, Hooman; Poutschi, Hossein; Khoshnia, Masoud; Norouzi, Alireza; Amiriani, Taghi; Sohrabpour, Amir Ali; Aliasgari, Ali; Jafari, Elham; Semnani, Shahryar; Abnet, Christian C.; Pharaoh, Paul D.; Brennan, Paul; Kamangar, Farin; Dawsey, Sanford M.; Boffetta, Paolo; Malekzadeh, Reza

    2014-01-01

    BACKGROUND Only a few studies in Western countries have investigated the association between gastroesophageal reflux disease (GERD) and mortality at the general population level and they have shown mixed results. This study investigated the association between GERD symptoms and overall and cause-specific mortality in a large prospective population-based study in Golestan Province, Iran. METHODS Baseline data on frequency, onset time, and patient-perceived severity of GERD symptoms were available for 50001 participants in the Golestan Cohort Study (GCS). We identified 3107 deaths (including 1146 circulatory and 470 cancer-related) with an average follow-up of 6.4 years and calculated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for multiple potential confounders. RESULTS Severe daily symptoms (defined as symptoms interfering with daily work or causing nighttime awakenings on a daily bases, reported by 4.3% of participants) were associated with cancer mortality (HR 1.48, 95% CI: 1.04-2.05). This increase was too small to noticeably affect overall mortality. Mortality was not associated with onset time or frequency of GERD and was not increased with mild to moderate symptoms. CONCLUSION We have observed an association with GERD and increased cancer mortality in a small group of individuals that had severe symptoms. Most patients with mild to moderate GERD can be re-assured that their symptoms are not associated with increased mortality. PMID:24872865

  13. Systemic and Disease-Specific Risk Factors in Vascular Dementia: Diagnosis and Prevention

    Directory of Open Access Journals (Sweden)

    Efraim Jaul

    2017-10-01

    Full Text Available In order to prevent the onset of vascular dementia (VaD in aging individuals, it is critical to detect clinically relevant vascular and systemic pathophysiological changes to signal the onset of its preceding prodromal stages. Identifying behavioral and neurobiological markers that are highly sensitive to VaD classification vs. other dementias is likely to assist in developing novel preventive treatment strategies that could delay the onset of disruptive psychomotor symptoms, decrease hospitalizations, and increase the quality of life in clinically-high-risk aging individuals. In light of empirical diagnostic and clinical findings associated with VaD pathophysiology, the current investigation will suggest a few clinically-validated biomarker measures of prodromal VaD cognitive impairments that are correlated with vascular symptomology, and VaD endophenotypes in non-demented aging people. In prodromal VaD individuals, distinguishing VaD from other dementias (e.g., Alzheimer's disease could facilitate specific early preventive interventions that significantly delay more severe cognitive deterioration or indirectly suppress the onset of dementia with vascular etiology. Importantly, the authors conclude that primary prevention strategies should examine aging individuals by employing comprehensive geriatric assessment approach, taking into account their medical history, and longitudinally noting their vascular, systemic, cognitive, behavioral, and clinical functional status. Secondary prevention strategies may include monitoring chronic medication as well as promoting programs that facilitate social interaction and every-day activities.

  14. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease.

    Science.gov (United States)

    Harvey, Ronée E; Coffman, Kirsten E; Miller, Virginia M

    2015-03-01

    In the era of individualized medicine, gaps in knowledge remain about sex-specific risk factors, diagnostic and treatment options that might reduce mortality from cardiovascular disease (CVD) and improve outcomes for both women and men. In this review, contributions of biological mechanisms involving the sex chromosomes and the sex hormones on the cardiovascular system will be discussed in relationship to the female-specific risk factors for CVD: hypertensive disorders of pregnancy, menopause and use of hormonal therapies for contraception and menopausal symptoms. Additionally, sex-specific factors to consider in the differential diagnosis and treatment of four prevalent CVDs (hypertension, stroke, coronary artery disease and congestive heart failure) will be reviewed with emphasis on areas where additional research is needed.

  15. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Tanaka

    2015-08-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use.

  16. Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists.

    Science.gov (United States)

    Ouyang, Pamela; Wenger, Nanette K; Taylor, Doris; Rich-Edwards, Janet W; Steiner, Meir; Shaw, Leslee J; Berga, Sarah L; Miller, Virginia M; Merz, Noel Bairey

    2016-01-01

    In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex-specific

  17. The peripheral artery questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease.

    Science.gov (United States)

    Spertus, John; Jones, Philip; Poler, Sherri; Rocha-Singh, Krishna

    2004-02-01

    The most common indication for treating patients with peripheral arterial disease is to improve their health status: their symptoms, function, and quality of life. Quantifying health status requires a valid, reproducible, and sensitive disease-specific measure. The Peripheral Artery Questionnaire (PAQ) is a 20-item questionnaire developed to meet this need by quantifying patients' physical limitations, symptoms, social function, treatment satisfaction, and quality of life. Psychometric and clinical properties of the PAQ were evaluated in a prospective cohort study of 44 patients undergoing elective percutaneous peripheral revascularization. To establish reproducibility, 2 assessments were performed 2 weeks apart and before revascularization. The change in scores before and 6 weeks after revascularization were used to determine the instruments' responsiveness and were compared with the Short Form-36 and the Walking Impairment Questionnaire. A series of cross-sectional analyses were performed to establish the construct validity of the PAQ. The 7 domains of the PAQ were internally reliable, with Cronbach alpha = 0.80 to 0.94. The test-retest reliability analyses revealed insignificant mean changes of 0.6 to 2.3 points (P = not significant for all). Conversely, the change after revascularization ranged from 13.7 to 41.9 points (P PAQ to clinical improvement. The PAQ Summary Scale was the most sensitive of all scales tested. Construct validity was established by demonstrating correlations with other measures of patient health status. The PAQ is a valid, reliable, and responsive disease-specific measure for patients with peripheral arterial disease. It may prove to be a useful end point in clinical trials and a potential aid in disease management.

  18. Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases.

    Science.gov (United States)

    Nexo, Mette Andersen; Watt, Torquil; Bonnema, Steen Joop; Hegedüs, Laszlo; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla; Bjorner, Jakob Bue

    2015-07-01

    We aimed to identify the best approach to work ability assessment in patients with thyroid disease by evaluating the factor structure, measurement equivalence, known-groups validity, and predictive validity of a broad set of work ability items. Based on the literature and interviews with thyroid patients, 24 work ability items were selected from previous questionnaires, revised, or developed anew. Items were tested among 632 patients with thyroid disease (non-toxic goiter, toxic nodular goiter, Graves' disease (with or without orbitopathy), autoimmune hypothyroidism, and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head-to-head comparisons of relative validity in distinguishing known groups. Although all work ability items loaded on a common factor, the optimal factor solution included five factors: role physical, role emotional, thyroid-specific limitations, work limitations (without disease attribution), and work performance. The scale on thyroid-specific limitations showed the most power in distinguishing clinical groups and time since diagnosis. A global single item proved useful for comparisons with the general population, and a thyroid-specific item predicted labor market exclusion within the next 5 years (OR 5.0, 95 % CI 2.7-9.1). Items on work limitations with attribution to thyroid disease were most effective in detecting impact on work ability and showed good predictive validity. Generic work ability items remain useful for general population comparisons.

  19. PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN.

    Science.gov (United States)

    Selleski, Nicole; Almeida, Lucas Malta; Almeida, Fernanda Coutinho de; Pratesi, Claudia Beatriz; Nóbrega, Yanna Karla de Medeiros; Gandolfi, Lenora

    2018-01-01

    Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

  20. PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN

    Directory of Open Access Journals (Sweden)

    Nicole SELLESKI

    Full Text Available ABSTRACT BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. OBJECTIVE: The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. METHODS: HLA-DQ typing was performed in samples from a group of celiac (n=100 and non-celiac children (n=110. All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5, DQA1*03-DQB1*03:02 (DQ8 and DQA1*02:01-DQB1*02:02 (DQ2.2. Fisher`s exact test was used for statistical analysis. RESULTS: In the group of 100 celiac children, 78 (78% were positive for DQ2, 13 (13 % were DQ2/DQ8 and 6 (6% were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9% samples, in 2 (1.8 % was positive for DQ2/DQ8 and in 15 (13.6% was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. CONCLUSION: The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

  1. Amino acids 16-275 of minute virus of mice NS1 include a domain that specifically binds (ACCA)2-3-containing DNA.

    Science.gov (United States)

    Mouw, M; Pintel, D J

    1998-11-10

    GST-NS1 purified from Escherichia coli and insect cells binds double-strand DNA in an (ACCA)2-3-dependent fashion under similar ionic conditions, independent of the presence of anti-NS1 antisera or exogenously supplied ATP and interacts with single-strand DNA and RNA in a sequence-independent manner. An amino-terminal domain (amino acids 1-275) of NS1 [GST-NS1(1-275)], representing 41% of the full-length NS1 molecule, includes a domain that binds double-strand DNA in a sequence-specific manner at levels comparable to full-length GST-NS1, as well as single-strand DNA and RNA in a sequence-independent manner. The deletion of 15 additional amino-terminal amino acids yielded a molecule [GST-NS1(1-275)] that maintained (ACCA)2-3-specific double-strand DNA binding; however, this molecule was more sensitive to increasing ionic conditions than full-length GST-NS1 and GST-NS1(1-275) and could not be demonstrated to bind single-strand nucleic acids. A quantitative filter binding assay showed that E. coli- and baculovirus-expressed GST-NS1 and E. coli GST-NS1(1-275) specifically bound double-strand DNA with similar equilibrium kinetics [as measured by their apparent equilibrium DNA binding constants (KD)], whereas GST-NS1(16-275) bound 4- to 8-fold less well. Copyright 1998 Academic Press.

  2. Vesiculo-erosive oral mucosal disease--management with topical corticosteroids: (1) Fundamental principles and specific agents available.

    Science.gov (United States)

    González-Moles, M A; Scully, C

    2005-04-01

    Vesiculo-erosive diseases of the oral mucosa pose a major challenge in oral medicine, because they are chronic, painful, and interfere with the daily activities and quality of life of the patients, including disturbing eating, drinking, talking, and personal relationships. Many are autoimmune diseases, and corticosteroid therapy is currently central to their treatment. These diseases present with inflammation and alterations to epithelial integrity, through cell and/or humoral immunity-mediated attack on epithelial-connective tissue targets. Until recently, despite their serious adverse effects, it was necessary to prescribe systemic corticosteroids to control severe erosive oral diseases. Now, however, many of these diseases can be controlled by high-potency topical corticosteroids, which have proved to be highly efficacious and to cause fewer adverse effects compared with systemic corticosteroids. Nevertheless, although topical corticosteroids are still the most widely used drugs in the practice of oral medicine, the scientific body of evidence for their use in the oral cavity is virtually non-existent, and therefore many of the protocols followed are, of necessity, drawn from experience of their use in a dermatological setting. This review aims to set out the key aspects of the use of topical corticosteroids in oral medicine. The issues covered include the indications and basic rules for their use, the types of corticosteroids, the drug selection, and the specific formulations.

  3. Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases.

    Science.gov (United States)

    Zhou, Yan; Proudnikov, Dmitri; Yuferov, Vadim; Kreek, Mary Jeanne

    2010-02-16

    From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and resultant changes in hormone levels, have been documented to occur after chronic intermittent exposure to heroin, morphine, other opiates, cocaine, other stimulants, and alcohol in animal models and in human molecular genetics. The best studied of the stress-responsive systems in humans and mammalian species in general is undoubtedly the HPA axis. In addition, there are stress-responsive systems in other parts in the brain itself, and some of these include components of the HPA axis, such as CRF and CRF receptors, along with POMC gene and gene products. Several other stress-responsive systems are known to influence the HPA axis, such as the vasopressin-vasopressin receptor system. Orexin-hypocretin, acting at its receptors, may effect changes which suggest that it should be properly categorized as a stress-responsive system. However, less is known about the interactions and connectivity of some of these different neuropeptide and receptor systems, and in particular, about the possible connectivity of fast-acting (e.g., glutamate and GABA) and slow-acting (including dopamine, serotonin, and norepinephrine) neurotransmitters with each of these stress-responsive components and the resultant impact, especially in the setting of chronic exposure to drugs of abuse. Several of these stress-responsive systems and components, primarily based on our laboratory-based and human molecular genetics research of addictive diseases, will be briefly discussed in this review. Copyright 2009 Elsevier B.V. All rights reserved.

  4. Cluster analysis of Helicobacter pylori genomic DNA fingerprints suggests gastroduodenal disease-specific associations.

    Science.gov (United States)

    Go, M F; Chan, K Y; Versalovic, J; Koeuth, T; Graham, D Y; Lupski, J R

    1995-07-01

    Helicobacter pylori infection is now accepted as the most common cause of chronic active gastritis and peptic ulcer disease. The etiologies of many infectious diseases have been attributed to specific or clonal strains of bacterial pathogens. Polymerase chain reaction (PCR) amplification of DNA between repetitive DNA sequences, REP elements (REP-PCR), has been utilized to generate DNA fingerprints to examine similarity among strains within a bacterial species. Genomic DNA from H. pylori isolates obtained from 70 individuals (39 duodenal ulcers and 31 simple gastritis) was PCR-amplified using consensus probes to repetitive DNA elements. The H. pylori DNA fingerprints were analyzed for similarity and correlated with disease presentation using the NTSYS-pc computer program. Each H. pylori strain had a distinct DNA fingerprint except for two pairs. Single-colony DNA fingerprints of H. pylori from the same patient were identical, suggesting that each patient harbors a single strain. Computer-assisted cluster analysis of the REP-PCR DNA fingerprints showed two large clusters of isolates, one associated with simple gastritis and the other with duodenal ulcer disease. Cluster analysis of REP-PCR DNA fingerprints of H. pylori strains suggests that duodenal ulcer isolates, as a group, are more similar to one another and different from gastritis isolates. These results suggest that disease-specific strains may exist.

  5. Calcific Aortic Valve Disease Is Associated with Layer-Specific Alterations in Collagen Architecture.

    Directory of Open Access Journals (Sweden)

    Heather N Hutson

    Full Text Available Disorganization of the valve extracellular matrix (ECM is a hallmark of calcific aortic valve disease (CAVD. However, while microarchitectural features of the ECM can strongly influence the biological and mechanical behavior of tissues, little is known about the ECM microarchitecture in CAVD. In this work, we apply advanced imaging techniques to quantify spatially heterogeneous changes in collagen microarchitecture in CAVD. Human aortic valves were obtained from individuals between 50 and 75 years old with no evidence of valvular disease (healthy and individuals who underwent valve replacement surgery due to severe stenosis (diseased. Second Harmonic Generation microscopy and subsequent image quantification revealed layer-specific changes in fiber characteristics in healthy and diseased valves. Specifically, the majority of collagen fiber changes in CAVD were found to occur in the spongiosa, where collagen fiber number increased by over 2-fold, and fiber width and density also significantly increased. Relatively few fibrillar changes occurred in the fibrosa in CAVD, where fibers became significantly shorter, but did not otherwise change in terms of number, width, density, or alignment. Immunohistochemical staining for lysyl oxidase showed localized increased expression in the diseased fibrosa. These findings reveal a more complex picture of valvular collagen enrichment and arrangement in CAVD than has previously been described using traditional analysis methods. Changes in fiber architecture may play a role in regulating the pathobiological events and mechanical properties of valves during CAVD. Additionally, characterization of the ECM microarchitecture can inform the design of fibrous scaffolds for heart valve tissue engineering.

  6. Negative cancer stereotypes and disease-specific self-concept in head and neck cancer.

    Science.gov (United States)

    Wong, Janice C; Payne, Ada Y M; Mah, Kenneth; Lebel, Sophie; Lee, Ruth N F; Irish, Jonathan; Rodin, Gary; Devins, Gerald M

    2013-05-01

    Life-threatening diseases, such as head and neck cancer (HNCa), can stimulate the emergence of a new disease-specific self-concept. We hypothesized that (i) negative cancer-stereotypes invoke distancing, which inhibits the adoption of a disease-specific self-concept and (ii) patient characteristics, disease and treatment factors, and cancer-related stressors moderate the phenomenon. Head and neck cancer outpatients (N = 522) completed a semantic-differential measure of disease-specific self-concept (perceived similarity to the 'cancer patient') and other self-report measures in structured interviews. Negative cancer-stereotypes were represented by the number of semantic-differential dimensions (0-3) along which respondents evaluated the stereotypic 'cancer patient' negatively (i.e., negative valence). We tested the two-way interactions between negative valence and hypothesized moderator variables. We observed significant negative valence × moderator interactions for the following: (i) patient characteristics (education, employment, social networks); (ii) disease and treatment factors (cancer-symptom burden); and (iii) cancer-related stressors (uncertainty, lack of information, and existential threats). Negative cancer stereotypes were consistently associated with distancing of self from the stereotypic 'cancer patient,' but the effect varied across moderator variables. All significant moderators (except employment and social networks) were associated with increasing perceived similarity to the 'cancer patient' when respondents maintained negative stereotypes; perceived similarity decreased when people were employed or had extensive social networks. Moderator effects were less pronounced when respondents did not endorse negative cancer stereotypes. When they hold negative stereotypes, people with HNCa distance themselves from a 'cancer patient' identity to preserve self-esteem or social status, but exposure to cancer-related stressors and adaptive demands may

  7. Disease-specific hashtags and the creation of Twitter medical communities in hematology and oncology.

    Science.gov (United States)

    Pemmaraju, Naveen; Thompson, Michael A; Qazilbash, Muzaffar

    2017-10-01

    Twitter is being increasingly used for information gathering and dissemination of ideas in both medical practice and scientific research. A major limitation to its use has been the surplus of available information and difficulty in categorizing that information into topics of individual interest. However, a Twitter feature known as the hashtag (#), which denotes a specific category or topic, helps in streamlining this wealth of information. The creation and adoption of disease-specific hashtags by healthcare stakeholders has led to a greater uniformity of medical discussions that can be retrieved and referenced at later time-points. As new disease-specific hashtags are created for hematologic and oncologic diseases, more users can connect across the world, even for the rarest of cancer subtypes. A major challenge for this emerging application will be the development of specific and easily identifiable hashtags over time to add more clarity, while still trying to grow Twitter users and expand its reach. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Specific Disruption of Hippocampal Mossy Fiber Synapses in a Mouse Model of Familial Alzheimer's Disease

    Science.gov (United States)

    Wilke, Scott A.; Raam, Tara; Antonios, Joseph K.; Bushong, Eric A.; Koo, Edward H.; Ellisman, Mark H.; Ghosh, Anirvan

    2014-01-01

    The earliest stages of Alzheimer's disease (AD) are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF) synapse between dentate gyrus (DG) and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM) to analyze MF microcircuitry in a mouse model of familial Alzheimer's disease (FAD). FAD mutant MF terminal complexes were severely disrupted compared to control – they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease. PMID:24454724

  9. Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

    Science.gov (United States)

    Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

  10. Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation.

    Science.gov (United States)

    Wagner, Monika; Khoury, Hanane; Willet, Jacob; Rindress, Donna; Goetghebeur, Mireille

    2016-03-01

    The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas. Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration. Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM. The adapted framework measures value in its widest sense, while being responsive to rare disease

  11. The role of self-efficacy in inflammatory bowel disease management: preliminary validation of a disease-specific measure.

    Science.gov (United States)

    Keefer, Laurie; Kiebles, Jennifer L; Taft, Tiffany H

    2011-02-01

    Inflammatory bowel diseases (IBDs) require self-management skills that may be influenced by self-efficacy (SE). Self-efficacy represents an individual's perception of his or her ability to organize and execute the behaviors necessary to manage disease. The goal of this study was to develop a valid and reliable measure of IBD-specific SE that can be used in clinical and research contexts. One hundred and twenty-two adults with a verified IBD diagnosis participated in the study. Data were pooled from 2 sources: patients from an outpatient university gastroenterology clinic (n=42) and a sample of online respondents (n=80). All participants (N=122) completed the IBD Self-Efficacy Scale (IBD-SES) and the Inflammatory Bowel Disease Questionnaire. Additionally, online participants completed the Brief Symptom Inventory-18 and the Rosenberg Self-Esteem Scale, whereas those in the clinic sample completed the Perceived Health Competence Scale, the Perceived Stress Questionnaire, and the Short Form Version 2 Health Survey. The IBD-SES was initially constructed to identify 4 distinct theoretical domains of self-efficacy: (1) managing stress and emotions, (2) managing medical care, (3) managing symptoms and disease, and (4) maintaining remission. The 29-item IBD-SES has high internal consistency (r=0.96), high test-retest reliability (r=0.90), and demonstrates strong construct and concurrent validity with established measures. The IBD-SES is a critical first step toward addressing an important psychological construct that could influence treatment outcomes in IBD.

  12. Current and investigational non-dopaminergic agents for management of motor symptoms (including motor complications) in Parkinson's disease.

    Science.gov (United States)

    Müller, Thomas

    2017-10-01

    Parkinson's disease is characterized by a heterogeneous combination of motor and non motor symptoms. The nigrostriatal dopamine deficit is one of its essential pathophysiologic features. Areas covered: This invited narrative review provides an overlook over current available and future promising non dopaminergic therapeutics to modulate altered dopaminergic neurotransmission in Parkinson's disease. Current research strategies aim to proof clinical efficacy by amelioration of motor symptoms and preponderant levodopa related movement fluctuations. These so-called motor complications are characterized by involuntary movements as a result of an overstimulation of the nigrostriatal dopaminergic system or by temporary recurrence of motor symptoms, when beneficial effects of dopamine substituting drugs vane. Expert opinion: Non dopaminergic modulation of dopamine replacement is currently mostly investigated in well defined and selected patients with motor complications to get approval. However, the world of daily maintenance of patients with its individually adapted, so-called personalised, therapy will determine the real value of these therapeutics. Here the clinical experience of the treating neurologists and the courage to use unconventional drug combinations are essential preconditions for successful treatments of motor and associated non motor complications in cooperation with the patients and their care giving surroundings.

  13. Specific capture of target bacteria onto sensor surfaces for infectious disease diagnosis

    International Nuclear Information System (INIS)

    Kim, Jong-Hoon; Inoue, Shinnosuke; Chung, Jae-Hyun; Cangelosi, Gerard A; Lee, Kyong-Hoon

    2014-01-01

    A long-sought goal for infectious disease care is a rapid and accurate diagnostic tool that is compatible with the needs of low-resource settings. To identify target biomarkers of infectious diseases, immunoassays utilizing the binding affinity between antigen and antibody have been widely used. In immunoassays, the interaction between antigen and antibody on sensor surfaces should be precisely controlled for specific identification of targets. This paper studies the specific capturing mechanisms of target bacteria onto sensor surfaces through investigation of combined effects of capillary action and binding affinity. As a model system, cells of both Escherichia coli and the Bacillus Calmette-Guérin strain of Mycobacterium bovis were used to study specific and nonspecific capturing mechanisms onto a microtip sensor. The capillary action was observed to arrange the concentrated cells onto the two-dimensional sensor surface. Due to the capillary-induced organization of target cells on the antibody-functionalized sensor surface, the number of the captured target cells was three times greater than that of the non-targeted cells. The capturing and detection capabilities varied with the width of a microtip. The specific capturing mechanism can be used to enhance the sensitivity and specificity of an immunoassay. (paper)

  14. EFFICACY OF COMBINATION TREATMENT WITH ANTI_IGE PLUS SPECIFIC IMMUNOTHERAPY IN PATIENTS WITH ATOPIC DISEASES

    Directory of Open Access Journals (Sweden)

    N.I. Il'ina

    2008-01-01

    Full Text Available Allergen specific immunotherapy (ASIT is a very effective technique in treatment of many allergic diseases. It greatly improves the quality of life. There's a risk of adverse system reactions at the time of ASIT. Treatment with anti Ige antibodies (omalizumab, xolair allows decreasing the circulating Ige level and lessening an expression of high affinity fc_r1 receptors on the surface of basophiles and mast cells, inhibition of early and late phase of allergic inflammatory response. Combination of antibige therapy and ASIT can lead to decrease of risk of adverse system reactions.Key words: omalizumab, anti Ige antibodies, allergen specific immunotherapy.

  15. Determining Specific Window Period for Common Scab Disease Infection in Potato Tubers

    Directory of Open Access Journals (Sweden)

    Bhim Bahadur Khatri

    2017-05-01

    Full Text Available A series of experiments was conducted under glasshouse and hydroponic conditions to determine the specific window period for common scab disease infection in potato tubers. The study was performed in a glasshouse system where separate tubers from the root zone were inoculated at different intervals during plant growth along with a novel hydroponic system to inoculate individual tubers at specific times of development growth allowing non-destructive observations of common scab symptoms developing. The window of tuber susceptibility to common scab disease infection was shown to vary with the season or conditions under which the plants were grown. Different internodes on tubers were found susceptible to infection at different times during tuber development. Basal internodes, which are the first sections of the tuber to expand, were susceptible to infection in the beginning of tuber development, whereas apical internodes only became susceptible later in tuber growth when the basal internodes were no longer susceptible.

  16. Bayesian Estimation of Fish Disease Prevalence from Pooled Samples Incorporating Sensitivity and Specificity

    Science.gov (United States)

    Williams, Christopher J.; Moffitt, Christine M.

    2003-03-01

    An important emerging issue in fisheries biology is the health of free-ranging populations of fish, particularly with respect to the prevalence of certain pathogens. For many years, pathologists focused on captive populations and interest was in the presence or absence of certain pathogens, so it was economically attractive to test pooled samples of fish. Recently, investigators have begun to study individual fish prevalence from pooled samples. Estimation of disease prevalence from pooled samples is straightforward when assay sensitivity and specificity are perfect, but this assumption is unrealistic. Here we illustrate the use of a Bayesian approach for estimating disease prevalence from pooled samples when sensitivity and specificity are not perfect. We also focus on diagnostic plots to monitor the convergence of the Gibbs-sampling-based Bayesian analysis. The methods are illustrated with a sample data set.

  17. Obstacles to implementing evidence-based practice in Belgium: a context-specific qualitative evidence synthesis including findings from different health care disciplines.

    Science.gov (United States)

    Hannes, K; Goedhuys, J; Aertgeerts, B

    2012-01-01

    A number of barriers to the implementation of evidence-based practice have already been inventoried. However, little attention has been given to their context-specific nature. This qualitative evidence synthesis examines commonalities in the obstacles perceived by different groups of health care practitioners working in the Belgian health care system and sets out to discuss potential strategies to bridge some of these barriers. We actively searched for primary studies addressing our topic of interest in international and national databases (1990 to May 2008), consulted experts and screened references of retrieved studies. We opted for the meta-aggregative approach, developed by the Joanna Briggs Institute, to analyse our findings. The findings indicate that (1) evidence might have a limited role in decision-making processes; (2) aspects other than quality of care steer the evidence-based practice agenda; (3) some health care providers benefit less from evidence-based practice than others and (4) there is a lack of competences to put the evidence-based principles in practice. Belgian policy makers might consider health care system characteristics from and strategies developed or suggested by others to respond to country-specific obstacles. Examples include but are not limited to; (a) providing incentives for patient-centred care coordination and patient communication, (b) supporting practitioners interested in applying research-related activities, (c) considering direct access systems and interprofessional learning to respond to the demand for autonomous decision-making from satellite professional groups, (d) systematically involving allied health professionals in important governmental advisory boards, (e) considering pharmaceutical companies perceived as 'the enemy' an ally in filling in research gaps, (f) embedding the evaluation of evidence-based knowledge and skills in examinations (g) moving from (in)formative learning to transformative learning and (h

  18. Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

    Directory of Open Access Journals (Sweden)

    María Cecilia Albareda

    2015-05-01

    Full Text Available The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease. T-helper (Th1 and interleukin (IL-10 Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively or vice versa, depending on the T. cruzi antigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruzi results from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

  19. Fragrance allergy and quality of life - development and validation of a disease-specific quality of life instrument.

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    Heisterberg, Maria V; Menné, Torkil; Johansen, Jeanne D

    2014-02-01

    Fragrance allergy is a lifelong condition that may give rise to permanent or recurrent contact dermatitis and may affect quality of life (QoL). The effect on QoL has not yet been investigated, and no disease-specific QoL instrument for fragrance allergy exists. To develop and validate a disease-specific instrument to investigate QoL among fragrance-allergic subjects. A fragrance QoL instrument (FQL index) was developed on the basis of narratives from 68 fragrance-allergic subjects, and consisted of 13 items. It was tested in a postal survey among 1650 participants patch tested at Gentofte University Hospital (2000–2010). The survey included other QoL instruments [Dermatology Life Quality Index (DLQI) and Short Form 36 (SF36) version 2] and questions on eczema severity (response rate of 66%). A retest was conducted after 3–6 months (response rate of 72.5%). The FQL index showed a significant and strong correlation with the DLQI (rS = 0.70), and disease severity, but a weak correlation with SF36 [mental component summary score, rS = − 0.22; physical component summary score, rS = − 0.31]. Good reliability and responsiveness to changes in disease severity were seen. The FQL index is a good instrument with which to investigate QoL in subjects with fragrance allergy. Good correlations with the DLQI and self-estimated disease severity were seen, and it showed good reliability, reproducibility and ability to distinguish changes in disease severity.

  20. Grey matter volume loss is associated with specific clinical motor signs in Huntington's disease.

    Science.gov (United States)

    Coppen, Emma M; Jacobs, Milou; van den Berg-Huysmans, Annette A; van der Grond, Jeroen; Roos, Raymund A C

    2018-01-01

    Motor disturbances are clinical hallmarks of Huntington's disease (HD) and involve chorea, dystonia, hypokinesia and visuomotor dysfunction. Investigating the association between specific motor signs and different regional volumes is important to understand the heterogeneity of HD. To investigate the motor phenotype of HD and associations with subcortical and cortical grey matter volume loss. Structural T1-weighted MRI scans of 79 HD patients and 30 healthy controls were used to calculate volumes of seven subcortical structures including the nucleus accumbens, hippocampus, thalamus, caudate nucleus, putamen, pallidum and amygdala. Multiple linear regression analyses, corrected for age, gender, CAG, MRI scan protocol and normalized brain volume, were performed to assess the relationship between subcortical volumes and different motor subdomains (i.e. eye movements, chorea, dystonia, hypokinesia/rigidity and gait/balance). Voxel-based morphometry analysis was used to investigate the relationship between cortical volume changes and motor signs. Subcortical volume loss of the accumbens nucleus, caudate nucleus, putamen, and pallidum were associated with higher chorea scores. No other subcortical region was significantly associated with motor symptoms after correction for multiple comparisons. Voxel-based cortical grey matter volume reductions in occipital regions were related with an increase in eye movement scores. In HD, chorea is mainly associated with subcortical volume loss, while eye movements are more related to cortical volume loss. Both subcortical and cortical degeneration has an impact on motor impairment in HD. This implies that there is a widespread contribution of different brain regions resulting in the clinical motor presentation seen in HD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Disease-specific quality of life in young patients with tourette syndrome.

    Science.gov (United States)

    Cavanna, Andrea E; Luoni, Chiara; Selvini, Claudia; Blangiardo, Rosanna; Eddy, Clare M; Silvestri, Paola R; Calì, Paola V; Gagliardi, Emanuela; Balottin, Umberto; Cardona, Francesco; Rizzo, Renata; Termine, Cristiano

    2013-02-01

    Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating "pure" Tourette syndrome from Tourette syndrome "plus" behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Inflammatory bowel disease-specific health-related quality of life instruments: a systematic review of measurement properties.

    Science.gov (United States)

    Chen, Xin-Lin; Zhong, Liang-Huan; Wen, Yi; Liu, Tian-Wen; Li, Xiao-Ying; Hou, Zheng-Kun; Hu, Yue; Mo, Chuan-Wei; Liu, Feng-Bin

    2017-09-15

    This review aims to critically appraise and compare the measurement properties of inflammatory bowel disease (IBD)-specific health-related quality of life instruments. Medline, EMBASE and ISI Web of Knowledge were searched from their inception to May 2016. IBD-specific instruments for patients with Crohn's disease, ulcerative colitis or IBD were enrolled. The basic characteristics and domains of the instruments were collected. The methodological quality of measurement properties and measurement properties of the instruments were assessed. Fifteen IBD-specific instruments were included, which included twelve instruments for adult IBD patients and three for paediatric IBD patients. All of the instruments were developed in North American and European countries. The following common domains were identified: IBD-related symptoms, physical, emotional and social domain. The methodological quality was satisfactory for content validity; fair in internal consistency, reliability, structural validity, hypotheses testing and criterion validity; and poor in measurement error, cross-cultural validity and responsiveness. For adult IBD patients, the IBDQ-32 and its short version (SIBDQ) had good measurement properties and were the most widely used worldwide. For paediatric IBD patients, the IMPACT-III had good measurement properties and had more translated versions. Most methodological quality should be promoted, especially measurement error, cross-cultural validity and responsiveness. The IBDQ-32 was the most widely used instrument with good reliability and validity, followed by the SIBDQ and IMPACT-III. Further validation studies are necessary to support the use of other instruments.

  3. Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

    Science.gov (United States)

    Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

    2018-04-12

    To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD

  4. Retrieval of radiology reports citing critical findings with disease-specific customization.

    Science.gov (United States)

    Lacson, Ronilda; Sugarbaker, Nathanael; Prevedello, Luciano M; Ivan, Ip; Mar, Wendy; Andriole, Katherine P; Khorasani, Ramin

    2012-01-01

    Communication of critical results from diagnostic procedures between caregivers is a Joint Commission national patient safety goal. Evaluating critical result communication often requires manual analysis of voluminous data, especially when reviewing unstructured textual results of radiologic findings. Information retrieval (IR) tools can facilitate this process by enabling automated retrieval of radiology reports that cite critical imaging findings. However, IR tools that have been developed for one disease or imaging modality often need substantial reconfiguration before they can be utilized for another disease entity. THIS PAPER: 1) describes the process of customizing two Natural Language Processing (NLP) and Information Retrieval/Extraction applications - an open-source toolkit, A Nearly New Information Extraction system (ANNIE); and an application developed in-house, Information for Searching Content with an Ontology-Utilizing Toolkit (iSCOUT) - to illustrate the varying levels of customization required for different disease entities and; 2) evaluates each application's performance in identifying and retrieving radiology reports citing critical imaging findings for three distinct diseases, pulmonary nodule, pneumothorax, and pulmonary embolus. Both applications can be utilized for retrieval. iSCOUT and ANNIE had precision values between 0.90-0.98 and recall values between 0.79 and 0.94. ANNIE had consistently higher precision but required more customization. Understanding the customizations involved in utilizing NLP applications for various diseases will enable users to select the most suitable tool for specific tasks.

  5. Cognitive training in Parkinson disease: cognition-specific vs nonspecific computer training.

    Science.gov (United States)

    Zimmermann, Ronan; Gschwandtner, Ute; Benz, Nina; Hatz, Florian; Schindler, Christian; Taub, Ethan; Fuhr, Peter

    2014-04-08

    In this study, we compared a cognition-specific computer-based cognitive training program with a motion-controlled computer sports game that is not cognition-specific for their ability to enhance cognitive performance in various cognitive domains in patients with Parkinson disease (PD). Patients with PD were trained with either a computer program designed to enhance cognition (CogniPlus, 19 patients) or a computer sports game with motion-capturing controllers (Nintendo Wii, 20 patients). The effect of training in 5 cognitive domains was measured by neuropsychological testing at baseline and after training. Group differences over all variables were assessed with multivariate analysis of variance, and group differences in single variables were assessed with 95% confidence intervals of mean difference. The groups were similar regarding age, sex, and educational level. Patients with PD who were trained with Wii for 4 weeks performed better in attention (95% confidence interval: -1.49 to -0.11) than patients trained with CogniPlus. In our study, patients with PD derived at least the same degree of cognitive benefit from non-cognition-specific training involving movement as from cognition-specific computerized training. For patients with PD, game consoles may be a less expensive and more entertaining alternative to computer programs specifically designed for cognitive training. This study provides Class III evidence that, in patients with PD, cognition-specific computer-based training is not superior to a motion-controlled computer game in improving cognitive performance.

  6. Targeting Specific HATs for Neurodegenerative Disease Treatment: Translating Basic Biology to Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    Sheila K. Pirooznia

    2013-03-01

    Full Text Available Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HATs activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and

  7. Why industry propaganda and political interference cannot disguise the inevitable role played by human exposure to aluminum in neurodegenerative diseases, including Alzheimer's disease.

    Science.gov (United States)

    Exley, Christopher

    2014-01-01

    In the aluminum age, it is clearly unpalatable for aluminum, the globe's most successful metal, to be implicated in human disease. It is unpalatable because for approximately 100 years human beings have reaped the rewards of the most abundant metal of the Earth's crust without seriously considering the potential consequences for human health. The aluminum industry is a pillar of the developed and developing world and irrespective of the tyranny of human exposure to aluminum it cannot be challenged without significant consequences for businesses, economies, and governments. However, no matter how deep the dependency or unthinkable the withdrawal, science continues to document, if not too slowly, a burgeoning body burden of aluminum in human beings. Herein, I will make the case that it is inevitable both today and in the future that an individual's exposure to aluminum is impacting upon their health and is already contributing to, if not causing, chronic diseases such as Alzheimer's disease. This is the logical, if uncomfortable, consequence of living in the aluminum age.

  8. Inferring relationships between clinical mastitis, productivity and fertility: a recursive model application including genetics, farm associated herd management, and cow-specific antibiotic treatments.

    Science.gov (United States)

    Rehbein, Pia; Brügemann, Kerstin; Yin, Tong; V Borstel, U König; Wu, Xiao-Lin; König, Sven

    2013-10-01

    A dataset of test-day records, fertility traits, and one health trait including 1275 Brown Swiss cows kept in 46 small-scale organic farms was used to infer relationships among these traits based on recursive Gaussian-threshold models. Test-day records included milk yield (MY), protein percentage (PROT-%), fat percentage (FAT-%), somatic cell score (SCS), the ratio of FAT-% to PROT-% (FPR), lactose percentage (LAC-%), and milk urea nitrogen (MUN). Female fertility traits were defined as the interval from calving to first insemination (CTFS) and success of a first insemination (SFI), and the health trait was clinical mastitis (CM). First, a tri-trait model was used which postulated the recursive effect of a test-day observation in the early period of lactation on liability to CM (LCM), and further the recursive effect of LCM on the following test-day observation. For CM and female fertility traits, a bi-trait recursive Gaussian-threshold model was employed to estimate the effects from CM to CTFS and from CM on SFI. The recursive effects from CTFS and SFI onto CM were not relevant, because CM was recorded prior to the measurements for CTFS and SFI. Results show that the posterior heritability for LCM was 0.05, and for all other traits, heritability estimates were in reasonable ranges, each with a small posterior SD. Lowest heritability estimates were obtained for female reproduction traits, i.e. h(2)=0.02 for SFI, and h(2)≈0 for CTFS. Posterior estimates of genetic correlations between LCM and production traits (MY and MUN), and between LCM and somatic cell score (SCS), were large and positive (0.56-0.68). Results confirm the genetic antagonism between MY and LCM, and the suitability of SCS as an indicator trait for CM. Structural equation coefficients describe the impact of one trait on a second trait on the phenotypic pathway. Higher values for FAT-% and FPR were associated with a higher LCM. The rate of change in FAT-% and in FPR in the ongoing lactation with

  9. Kinetics of Hydrogen Radical Reactions with Toluene Including Chemical Activation Theory Employing System-Specific Quantum RRK Theory Calibrated by Variational Transition State Theory.

    Science.gov (United States)

    Bao, Junwei Lucas; Zheng, Jingjing; Truhlar, Donald G

    2016-03-02

    Pressure-dependent reactions are ubiquitous in combustion and atmospheric chemistry. We employ a new calibration procedure for quantum Rice-Ramsperger-Kassel (QRRK) unimolecular rate theory within a chemical activation mechanism to calculate the pressure-falloff effect of a radical association with an aromatic ring. The new theoretical framework is applied to the reaction of H with toluene, which is a prototypical reaction in the combustion chemistry of aromatic hydrocarbons present in most fuels. Both the hydrogen abstraction reactions and the hydrogen addition reactions are calculated. Our system-specific (SS) QRRK approach is adjusted with SS parameters to agree with multistructural canonical variational transition state theory with multidimensional tunneling (MS-CVT/SCT) at the high-pressure limit. The new method avoids the need for the usual empirical estimations of the QRRK parameters, and it eliminates the need for variational transition state theory calculations as a function of energy, although in this first application we do validate the falloff curves by comparing SS-QRRK results without tunneling to multistructural microcanonical variational transition state theory (MS-μVT) rate constants without tunneling. At low temperatures, the two approaches agree well with each other, but at high temperatures, SS-QRRK tends to overestimate falloff slightly. We also show that the variational effect is important in computing the energy-resolved rate constants. Multiple-structure anharmonicity, torsional-potential anharmonicity, and high-frequency-mode vibrational anharmonicity are all included in the rate computations, and torsional anharmonicity effects on the density of states are investigated. Branching fractions, which are both temperature- and pressure-dependent (and for which only limited data is available from experiment), are predicted as a function of pressure.

  10. Deriving site-specific soil clean-up values for metals and metalloids: rationale for including protection of soil microbial processes.

    Science.gov (United States)

    Kuperman, Roman G; Siciliano, Steven D; Römbke, Jörg; Oorts, Koen

    2014-07-01

    Although it is widely recognized that microorganisms are essential for sustaining soil fertility, structure, nutrient cycling, groundwater purification, and other soil functions, soil microbial toxicity data were excluded from the derivation of Ecological Soil Screening Levels (Eco-SSL) in the United States. Among the reasons for such exclusion were claims that microbial toxicity tests were too difficult to interpret because of the high variability of microbial responses, uncertainty regarding the relevance of the various endpoints, and functional redundancy. Since the release of the first draft of the Eco-SSL Guidance document by the US Environmental Protection Agency in 2003, soil microbial toxicity testing and its use in ecological risk assessments have substantially improved. A wide range of standardized and nonstandardized methods became available for testing chemical toxicity to microbial functions in soil. Regulatory frameworks in the European Union and Australia have successfully incorporated microbial toxicity data into the derivation of soil threshold concentrations for ecological risk assessments. This article provides the 3-part rationale for including soil microbial processes in the development of soil clean-up values (SCVs): 1) presenting a brief overview of relevant test methods for assessing microbial functions in soil, 2) examining data sets for Cu, Ni, Zn, and Mo that incorporated soil microbial toxicity data into regulatory frameworks, and 3) offering recommendations on how to integrate the best available science into the method development for deriving site-specific SCVs that account for bioavailability of metals and metalloids in soil. Although the primary focus of this article is on the development of the approach for deriving SCVs for metals and metalloids in the United States, the recommendations provided in this article may also be applicable in other jurisdictions that aim at developing ecological soil threshold values for protection of

  11. A new method for discovering disease-specific MiRNA-target regulatory networks.

    Directory of Open Access Journals (Sweden)

    Miriam Baglioni

    Full Text Available Genes and their expression regulation are among the key factors in the comprehension of the genesis and development of complex diseases. In this context, microRNAs (miRNAs are post-transcriptional regulators that play an important role in gene expression since they are frequently deregulated in pathologies like cardiovascular disease and cancer. In vitro validation of miRNA--targets regulation is often too expensive and time consuming to be carried out for every possible alternative. As a result, a tool able to provide some criteria to prioritize trials is becoming a pressing need. Moreover, before planning in vitro experiments, the scientist needs to evaluate the miRNA-target genes interaction network. In this paper we describe the miRable method whose purpose is to identify new potentially relevant genes and their interaction networks associate to a specific pathology. To achieve this goal miRable follows a system biology approach integrating together general-purpose medical knowledge (literature, Protein-Protein Interaction networks, prediction tools and pathology specific data (gene expression data. A case study on Prostate Cancer has shown that miRable is able to: 1 find new potential miRNA-targets pairs, 2 highlight novel genes potentially involved in a disease but never or little studied before, 3 reconstruct all possible regulatory subnetworks starting from the literature to expand the knowledge on the regulation of miRNA regulatory mechanisms.

  12. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

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    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  13. Development of a disease-specific instrument to measure quality of life in patients with alopecia areata.

    Science.gov (United States)

    Endo, Yuichiro; Miyachi, Yoshiki; Arakawa, Akiko

    2012-01-01

    Alopecia areata (AA) is a common hair loss disorder that frequently follows a chronic course. Although AA is apparently associated with disturbance of quality of life (QoL), no disease-specific instrument to measure the QoL has been developed. This study was conducted to develop a disease-specific self-administered instrument to measure AA patients' QoL (AAQ). A two-step cross-sectional study was conducted. Items were generated from qualitative interviews with five patients with AA (two men and three women, age 28±6.4 years). Then, a preliminary questionnaire was produced and delivered to the patients (n=122). The AAQ was examined in terms of statistical performance. The AAQ included 7 items in the following three subscales: 'restriction of activity', 'concealment' and 'adaptation'. The reliability of internal consistency was fair with Cronbach's alpha coefficients of 0.59-81 for each subscale. Confirmatory factor analysis and correlation analysis demonstrated that the AAQ had good construct validity. Interestingly, the AAQ was only correlated with subjective severity scores as rated by the patients, but not with objective disease severity assessed by investigators.

  14. Lung fibrosis quantified by HRCT in scleroderma patients with different disease forms and ANA specificities

    Directory of Open Access Journals (Sweden)

    S. Mancin

    2011-09-01

    Full Text Available Objective: to define the prevalence of interstitial lung fibrosis in systemic sclerosis (SSc and its relationship with the different clinical forms of disease and ANA specificities. Methods: fifty patients with SSc were submitted to pulmonary high resolution computed tomography (HRCT. Lung abnormalities were evaluated according to Warrick’s score that considers both the severity and the extent of fibrotic lesions. Results: pulmonary HRCT abnormalities were observed in 84% of SSc patients. Ground glass aspects (60%, irregular pleural margins (56% and septal/subpleural lines (68% were the most common lesions. The distribution of these abnormalities favoured the posterior basilar segments of both lungs. HRCT findings were significantly more frequent in males and in patients with the cutaneous diffuse form of SSc and with the specific antibody anti-Scl70. Conclusions: HRCT is a very useful method for the diagnosis of interstitial lung fibrosis in SSc. Warrick’s score permits to quantify the HRCT findings and to evaluate their relationship with the disease clinical forms and ANA specificities.

  15. Different Temporal Patterns of Specific and General Autobiographical Memories across the Lifespan in Alzheimer's Disease.

    Science.gov (United States)

    Philippi, Nathalie; Rousseau, François; Noblet, Vincent; Botzung, Anne; Després, Olivier; Cretin, Benjamin; Kremer, Stéphane; Blanc, Frédéric; Manning, Liliann

    2015-01-01

    We compared specific (i.e., associated with a unique time and space) and general (i.e., extended or repeated events) autobiographical memories (AbM) in Alzheimer's disease (AD). The comparison aims at investigating the relationship between these two components of AbM across the lifespan and the volume of cerebral regions of interest within the temporal lobe. We hypothesized that the ability to elicit specific memories would correlate with hippocampal volume, whereas evoking general memories would be related to lateral temporal lobe. AbM was assessed using the modified Crovitz test in 18 patients with early AD and 18 matched controls. The proportions of total memories-supposed to reflect the ability to produce general memories-and specific memories retrieved were compared between AD patients and controls. Correlations to MRI volumes of temporal cortex were tested. We found different temporal patterns for specific and general memories in AD patients, with (i) relatively spared general memories, according to a temporal gradient that preserved remote memories, predominantly associated with right lateral temporal cortex volume. (ii) Conversely, the retrieval of specific AbMs was impaired for all life periods and correlated with bilateral hippocampal volumes. Our results highlight a shift from an initially episodic to a semantic nature of AbMs during AD, where the abstracted form of memories remains.

  16. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    Directory of Open Access Journals (Sweden)

    Matthis Synofzik

    2014-01-01

    Full Text Available The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”. The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability. Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease.

  17. The research of Proactive Coping Behavior of Patients with Chronic Non-Specific Lung Disease

    Directory of Open Access Journals (Sweden)

    Marija A. Yaroslavskaya

    2011-01-01

    Full Text Available The purpose of the research was to study the patterns of using proactive coping and adherences to it's different types in patients with chronic non-specifi c lung diseases. Participants of the study (N=180 were 30 to 60 years old. The Proactive Coping Inventory was used to assess the patients' psychological status. According to the results of the study patients with chronic non-specifi c lung diseases use dif-ferent types of proactive coping behavior while solving problematic and stressful situations. The research revealed that patients with bronchial asthma don't have the skills of independent decision making, definition of objectives, considering of options in solving conflicts or other inconvenient situations sufficiently developed. Patients with chronic obstructive pulmonary disease are less satisfied with the emotional support that they receive from their relatives and closest people, it's harder for them to reveal their feelings and emotions than for those who suffer from bronchial asthma and healthy ones. The results of the study may be useful in developing educational systems of proactive coping behavior skills for patients with chronic non-specific lung diseases for their health and well-being support.

  18. BIOCONTROL FOR RHIZOCTONIA STEM ROT DISEASE BY USING COMBINATION OF SPECIFIC ENDOPHYTE IN PADDY TIDAL SWAMP

    Directory of Open Access Journals (Sweden)

    Ismed Setya Budi

    2013-10-01

    Full Text Available The use of combination of specific endophytic in tidal swamps to control stem root disease as biological control agents has not been done. It is expected that this combination is able to continuously protect plants from pathogen interference. The research was carried out in type C tidal swamp in Banjar regency of South Kalimantan, from March to November 2011, temperature 29-32oC, and pH 4.0-5.5. The method used was Split Plot design. Biocontrol preparation for both types of endophytic was applied in seeds in 7 days after planting (DAP. Observation on high intensity and plant diseases of planting stage on tidal swamps (taradak, ampak and lacak was conducted. The results showed that there was a reduction of disease ranging from 58.70 to 87.29%. The application of combination of two biocontrol agents (T. viride PS-2.1 + P. fluorescent PS-4.8, (Fusarium non-pathogenic PS-1.5 + P. fluorescent PS-4.8 and (T. viride PS-2.1+ FNP PS-1.5 isolate gave the best inhibition result, reduced disease intensity, and increased plant height. The result of soil analysis before and after application of endophytic showed that there was an increase in soil fertility with the element addition of N, P, K and pH.

  19. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    Science.gov (United States)

    2014-01-01

    The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

  20. Health-related quality of life of food allergic patients measured with generic and disease-specific questionnaires

    NARCIS (Netherlands)

    Flokstra-de Blok, B. M. J.; van der Velde, J. L.; Vlieg-Boerstra, B. J.; Oude Elberink, J. N. G.; DunnGalvin, A.; Hourihane, J. O.'B.; Duiverman, E. J.; Dubois, A. E. J.

    2010-01-01

    Health-related quality of life (HRQL) has never been measured with both generic and disease-specific questionnaires in the same group of food allergic patients. The aim of this study was to compare HRQL of food allergic patients as measured with generic and disease-specific questionnaires. Generic

  1. Health-related quality of life of food allergic patients measured with generic and disease-specific questionnaires

    NARCIS (Netherlands)

    Flokstra-de Blok, B. M. J.; van der Velde, J. L.; Vlieg-Boerstra, B. J.; Oude Elberink, J. N. G.; DunnGalvin, A.; Hourihane, J. O'B.; Duiverman, E. J.; Dubois, A. E. J.

    P>Background: Health-related quality of life (HRQL) has never been measured with both generic and disease-specific questionnaires in the same group of food allergic patients. The aim of this study was to compare HRQL of food allergic patients as measured with generic and disease-specific

  2. Prostate-specific antigen-positive extramammary Paget's disease--association with prostate cancer

    DEFF Research Database (Denmark)

    Hammer, Anne; Hager, Henrik; Steiniche, Torben

    2008-01-01

    Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that primarily affects the anogenital region. Cases of EMPD reacting with PSA (prostate-specific antigen) have previously been associated with underlying prostate cancer. However, a recent case of EMPD in our department has...... led us to question the value of PSA as an indicator of underlying prostate cancer. Clinical and pathological data were obtained for 16 cases of EMPD. Formalin-fixed, paraffin-embedded tissue blocks from the primary skin lesions were investigated using PSA and other immunohistochemical markers. 5...... of the 16 cases of EMPD stained positive for PSA (2 women and 3 men). However, no reactivity was seen for the prostatic marker P501S. Three of the five patients had been diagnosed with internal malignant disease-two with prostate cancer, stage 1. Immunohistochemical investigations of the tumour specimens...

  3. Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Hajime Otani

    2013-01-01

    Full Text Available Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span.

  4. Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific

    International Nuclear Information System (INIS)

    Taki, Junichi; Nakajima, Kenichi; Hwang, Eui-Hyo; Matsunari, Ichiro; Tonami, Norihisa; Komai, Kiyonobu; Yoshita, Mitsuhiro; Sakajiri, Kenichi

    2000-01-01

    The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63±9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61±0.29) was significantly lower than that in the control group (2.24±0.14, P<0.01), P-nism (2.15±0.31, P<0.01), MSA (2.08±0.31, P<0.05) and PSP (2.30±0.24, P<0.01). The delayed H/M ratio in PD (1.47±0.34) was also significantly lower than that in the control group (2.37±0.14, P<0.01), P-nism (2.13±0.38, P<0.01), PSP (2.36±0.36, P<0.01) and MSA (2.17±0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%±8.0% vs 11%±4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA

  5. Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific

    Energy Technology Data Exchange (ETDEWEB)

    Taki, Junichi; Nakajima, Kenichi; Hwang, Eui-Hyo; Matsunari, Ichiro; Tonami, Norihisa [Department of Nuclear Medicine, Kanazawa University School of Medicine, Kanazawa (Japan); Komai, Kiyonobu; Yoshita, Mitsuhiro; Sakajiri, Kenichi [Department of the Neurology, Kanazawa University School of Medicine, Kanazawa (Japan)

    2000-05-01

    The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63{+-}9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61{+-}0.29) was significantly lower than that in the control group (2.24{+-}0.14, P<0.01), P-nism (2.15{+-}0.31, P<0.01), MSA (2.08{+-}0.31, P<0.05) and PSP (2.30{+-}0.24, P<0.01). The delayed H/M ratio in PD (1.47{+-}0.34) was also significantly lower than that in the control group (2.37{+-}0.14, P<0.01), P-nism (2.13{+-}0.38, P<0.01), PSP (2.36{+-}0.36, P<0.01) and MSA (2.17{+-}0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%{+-}8.0% vs 11%{+-}4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of

  6. Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Fischer-Walker, Christa L; Lanata, Claudio F

    2015-01-01

    Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the gl...

  7. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

    Directory of Open Access Journals (Sweden)

    Chongsheng Qian

    2017-05-01

    Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT, the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB. Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9% or a third party haploidentical donor (57.1%. One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%. Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV

  8. Optimizing Staining Protocols for Laser Microdissection of Specific Cell Types from the Testis Including Carcinoma In Situ

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Dalgaard, Marlene D; Nielsen, John Erik

    2009-01-01

    Microarray and RT-PCR based methods are important tools for analysis of gene expression; however, in tissues containing many different cells types, such as the testis, characterization of gene expression in specific cell types can be severely hampered by noise from other cells. The laser microdis......Microarray and RT-PCR based methods are important tools for analysis of gene expression; however, in tissues containing many different cells types, such as the testis, characterization of gene expression in specific cell types can be severely hampered by noise from other cells. The laser...... protocols, and present two staining protocols for frozen sections, one for fast and specific staining of fetal germ cells, testicular carcinoma in situ cells, and other cells with embryonic stem cell-like properties that express the alkaline phosphatase, and one for specific staining of lipid droplet...

  9. Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

    DEFF Research Database (Denmark)

    Samuelsen, Simone V; Solov'yov, Ilia A.; Balboni, Imelda M.

    2016-01-01

    New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing...... molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best...... that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies....

  10. Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; Meine, Mathias

    2016-01-01

    of beta-blockers, use of psychotropic medication, anxiety, depression, and type D personality were found to be associated with poorer health status in unadjusted analyses. Interestingly, subgroups of patients (12-20 %) who experienced poor health status at baseline improved to stable good health status....... The timely identification of CRT-D patients who present with poor disease-specific health status (i.e., KCCQ score anxiety, depression, and/or type D personality) is paramount, as they may benefit from cardiac rehabilitation in combination...

  11. Biocontrol for Rhizoctonia Stem Rot Disease by Using Combination of Specific Endophyte in Paddy Tidal Swamp

    OpenAIRE

    Budi, Ismed Setya; Mariana, Mariana

    2013-01-01

    The use of combination of specific endophytic in tidal swamps to control stem root disease as biological control agents has not been done. It is expected that this combination is able to continuously protect plants from pathogen interference. The research was carried out in type C tidal swamp in Banjar regency of South Kalimantan, from March to November 2011, temperature 29-32oC, and pH 4.0-5.5. The method used was Split Plot design. Biocontrol preparation for both types of endophytic was ap...

  12. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Hansen, Niclas Tue; Karlberg, Erik, Olof, Linnart

    2008-01-01

    to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also......Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were...

  13. Strain-Specific Altered Regulatory Response of Rab7a and Tau in Creutzfeldt-Jakob Disease and Alzheimer's Disease.

    Science.gov (United States)

    Zafar, Saima; Younas, Neelam; Correia, Susana; Shafiq, Mohsin; Tahir, Waqas; Schmitz, Matthias; Ferrer, Isidre; Andréoletti, Olivier; Zerr, Inga

    2017-01-01

    There is an increasing demand for the understanding of pathophysiology on neurodegeneration diseases at early stages. Changes in endocytic machinery and the cytoskeleton-associated response are the first alterations observed in Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease AD brain. In this study, we performed a targeted search for endocytic pathway proteins in the different regions of the brain. We found late endosome marker Rab7a which was significantly upregulated in the frontal cortex region in the rapid progressive CJD form (MM1) and rapid progressive AD (rpAD) forms. However, Rab9 expression was significantly downregulated only in CJD-MM1 brain frontal cortex region. In the cerebellum, Rab7a expression showed significant upregulation in both subtype MM1 and VV2 CJD forms, in contrast to Rab9 which showed significant downregulation in both subtype MM1 and VV2 CJD forms at terminal stage of the disease. To check regulatory response at pre-symptomatic stage of the disease, we checked the regulatory interactive response of Rab7a, Rab9, and known biomarkers PrP C and tau forms in frontal cortex at pre-symptomatic stage of the disease in tg340 mice expressing about fourfold of human PrP-M129 with PrP-null background that had been inoculated with human sCJD MM1 brain tissue homogenates (sCJD MM1 mice). In addition, we analyzed 5XFAD mice, exhibiting five mutations in the APP and presenilin genes related to familial Alzheimer's disease (FAD), to validate specific regulatory response of Rab7a, Rab9, tau, and phosphorylated form of tau by immunostaining 5XFAD mice in comparison with the wild-type age-matched mice brain. The cortical region of 5XFAD mice brain showed accumulated form of Rab7a in puncta that co-label for p-Tau, indicating colocalization by using confocal laser-scanning microscopy and was confirmed by using reverse co-immunoprecipitation. Furthermore, synthetic RNA (siRNA) against the Rab7a gene decreased expression of Rab7a protein, in cortical

  14. A Comparison of Spatio-Temporal Disease Mapping Approaches Including an Application to Ischaemic Heart Disease in New South Wales, Australia

    Directory of Open Access Journals (Sweden)

    Craig Anderson

    2017-02-01

    Full Text Available The field of spatio-temporal modelling has witnessed a recent surge as a result of developments in computational power and increased data collection. These developments allow analysts to model the evolution of health outcomes in both space and time simultaneously. This paper models the trends in ischaemic heart disease (IHD in New South Wales, Australia over an eight-year period between 2006 and 2013. A number of spatio-temporal models are considered, and we propose a novel method for determining the goodness-of-fit for these models by outlining a spatio-temporal extension of the Moran’s I statistic. We identify an overall decrease in the rates of IHD, but note that the extent of this health improvement varies across the state. In particular, we identified a number of remote areas in the north and west of the state where the risk stayed constant or even increased slightly.

  15. Age-specific epigenetic drift in late-onset Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Sun-Chong Wang

    Full Text Available Despite an enormous research effort, most cases of late-onset Alzheimer's disease (LOAD still remain unexplained and the current biomedical science is still a long way from the ultimate goal of revealing clear risk factors that can help in the diagnosis, prevention and treatment of the disease. Current theories about the development of LOAD hinge on the premise that Alzheimer's arises mainly from heritable causes. Yet, the complex, non-Mendelian disease etiology suggests that an epigenetic component could be involved. Using MALDI-TOF mass spectrometry in post-mortem brain samples and lymphocytes, we have performed an analysis of DNA methylation across 12 potential Alzheimer's susceptibility loci. In the LOAD brain samples we identified a notably age-specific epigenetic drift, supporting a potential role of epigenetic effects in the development of the disease. Additionally, we found that some genes that participate in amyloid-beta processing (PSEN1, APOE and methylation homeostasis (MTHFR, DNMT1 show a significant interindividual epigenetic variability, which may contribute to LOAD predisposition. The APOE gene was found to be of bimodal structure, with a hypomethylated CpG-poor promoter and a fully methylated 3'-CpG-island, that contains the sequences for the epsilon4-haplotype, which is the only undisputed genetic risk factor for LOAD. Aberrant epigenetic control in this CpG-island may contribute to LOAD pathology. We propose that epigenetic drift is likely to be a substantial mechanism predisposing individuals to LOAD and contributing to the course of disease.

  16. Self-reported dietary adherence, disease-specific symptoms, and quality of life are associated with healthcare provider follow-up in celiac disease.

    Science.gov (United States)

    Hughey, Jacob J; Ray, Bonnie K; Lee, Anne R; Voorhees, Kristin N; Kelly, Ciaran P; Schuppan, Detlef

    2017-12-11

    The only treatment for celiac disease (CeD) is a lifelong gluten-free diet (GFD). The restrictive nature of the GFD makes adherence a challenge. As an integral part of CeD management, multiple professional organizations recommend regular follow-up with a healthcare provider (HCP). Many CeD patients also participate in patient advocacy groups (PAGs) for education and support. Previous work found that follow-up of CeD patients is highly variable. Here we investigated the self-reported factors associated with HCP follow-up among individuals diagnosed with CeD who participate in a PAG. We conducted a survey of members of Beyond Celiac (a PAG), collecting responses from 1832 U.S. adults ages 19-65 who reported having CeD. The survey queried HCP follow-up related to CeD and included validated instruments for dietary adherence (CDAT), disease-specific symptoms (CSI), and quality of life (CD-QOL). Overall, 27% of respondents diagnosed with CeD at least five years ago reported that they had not visited an HCP about CeD in the last five years. The most frequent reason for not visiting an HCP was "doing fine on my own" (47.6%). Using multiple logistic regression, we identified significant associations between whether a respondent reported visiting an HCP about CeD in the last five years and the scores for all three validated instruments. In particular, as disease-specific symptoms and quality of life worsened, the probability of having visited an HCP increased. Conversely, as dietary adherence worsened, the probability decreased. Our results suggest that many individuals with CeD manage their disease without ongoing support from an HCP. Our results thus emphasize the need for greater access to high quality CeD care, and highlight an opportunity for PAGs to bring together patients and HCPs to improve management of CeD.

  17. Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states

    Directory of Open Access Journals (Sweden)

    Cunningham TJ

    2014-09-01

    Full Text Available Timothy J Cunningham,1 Earl S Ford,1 Janet B Croft,1 Melissa T Merrick,2 Italia V Rolle,3 Wayne H Giles1 1Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA; 2Division of Violence Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA; 3Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA Purpose: Adverse childhood experiences (ACEs before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD in the general population. Materials and methods: Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs and their corresponding 95% confidence intervals (CIs for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Results: Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61, sexual abuse (PR =1.69, 95% CI: 1.36, 2.10, living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81, witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72, and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80 during childhood compared to those with no individual ACEs

  18. Cost-effectiveness of a disease-specific oral nutritional support for pressure ulcer healing.

    Science.gov (United States)

    Cereda, Emanuele; Klersy, Catherine; Andreola, Manuela; Pisati, Roberto; Schols, Jos M G A; Caccialanza, Riccardo; D'Andrea, Federico

    2017-02-01

    The Oligo Element Sore Trial has shown that supplementation with a disease-specific nutritional formula enriched with arginine, zinc, and antioxidants improves pressure ulcer (PU) healing in malnourished patients compared to an isocaloric-isonitrogenous support. However, the use of such a nutritional formula needs to be supported also by a cost-effectiveness evaluation. This economic evaluation - from a local healthcare system perspective - was conducted alongside a multicenter, randomized, controlled trial following a piggy-back approach. The primary efficacy endpoint was the percentage of change in PU area at 8 weeks. The cost analysis focused on: the difference in direct medical costs of local PU care between groups and incremental cost-effectiveness ratio (ICER) of nutritional therapy related to significant study endpoints (percentage of change in PU area and ≥40% reduction in PU area at 8 weeks). Although the experimental formula was more expensive (mean difference: 39.4 Euros; P costs of local PU care (difference, -74.3 Euros; P = 0.013). Therefore, given its efficacy it proved to be a cost-effective intervention. The robustness of these results was confirmed by the sensitivity analyses. The use of a disease-specific oral nutritional formula not only results in better healing of PUs, but also reduces the costs of local PU care from a local healthcare system perspective. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. Disease-Specific Trends of Comorbidity Coding and Implications for Risk Adjustment in Hospital Administrative Data.

    Science.gov (United States)

    Nimptsch, Ulrike

    2016-06-01

    To investigate changes in comorbidity coding after the introduction of diagnosis related groups (DRGs) based prospective payment and whether trends differ regarding specific comorbidities. Nationwide administrative data (DRG statistics) from German acute care hospitals from 2005 to 2012. Observational study to analyze trends in comorbidity coding in patients hospitalized for common primary diseases and the effects on comorbidity-related risk of in-hospital death. Comorbidity coding was operationalized by Elixhauser diagnosis groups. The analyses focused on adult patients hospitalized for the primary diseases of heart failure, stroke, and pneumonia, as well as hip fracture. When focusing the total frequency of diagnosis groups per record, an increase in depth of coding was observed. Between-hospital variations in depth of coding were present throughout the observation period. Specific comorbidity increases were observed in 15 of the 31 diagnosis groups, and decreases in comorbidity were observed for 11 groups. In patients hospitalized for heart failure, shifts of comorbidity-related risk of in-hospital death occurred in nine diagnosis groups, in which eight groups were directed toward the null. Comorbidity-adjusted outcomes in longitudinal administrative data analyses may be biased by nonconstant risk over time, changes in completeness of coding, and between-hospital variations in coding. Accounting for such issues is important when the respective observation period coincides with changes in the reimbursement system or other conditions that are likely to alter clinical coding practice. © Health Research and Educational Trust.

  20. KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility

    Science.gov (United States)

    Ragazzo, Michele; Manzo, Laura; Costanza, Gaetana; Bowes, John; Hüffmeier, Ulrike; Potenza, Saverio; Sangiuolo, Federica; Reis, André; Barton, Anne; Novelli, Giuseppe; Orlandi, Augusto; Giardina, Emiliano

    2017-01-01

    To date, the genes associated with Psoriatic Arthritis (PsA) are principally involved in inflammation, immune response and epidermal differentiation, without any information about the relationship between disease and bone metabolism genes. Our work was focused on 5q31 locus, which contains several genetic variants significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426 PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs of interest by Real Time PCR and direct sequencing. The results were subjected to biostatistic and bioinformatic analysis. The case-control study highlighted a significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD) study showed the presence of a specific block in high LD within 132,692,628-132,737,638 bp of 5q31, giving additional evidence of specific association of the 5q31 region in PsA patients. Moreover, KIF3A expression was assessed by immunohistochemistry assays which showed a marked and significant difference of KIF3A expression between pathological and normal tissues. Our analysis described KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear implication of bone metabolism genes in the disease etiopathogenesis. PMID:29221136

  1. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease.

    Science.gov (United States)

    McEachern, Kerry Anne; Fung, John; Komarnitsky, Svetlana; Siegel, Craig S; Chuang, Wei-Lien; Hutto, Elizabeth; Shayman, James A; Grabowski, Gregory A; Aerts, Johannes M F G; Cheng, Seng H; Copeland, Diane P; Marshall, John

    2007-07-01

    An approach to treating Gaucher disease is substrate inhibition therapy which seeks to abate the aberrant lysosomal accumulation of glucosylceramide. We have identified a novel inhibitor of glucosylceramide synthase (Genz-112638) and assessed its activity in a murine model of Gaucher disease (D409V/null). Biochemical characterization of Genz-112638 showed good potency (IC(50) approximately 24nM) and specificity against the target enzyme. Mice that received drug prior to significant accumulation of substrate (10 weeks of age) showed reduced levels of glucosylceramide and number of Gaucher cells in the spleen, lung and liver when compared to age-matched control animals. Treatment of older mice that already displayed significant amounts of tissue glucosylceramide (7 months old) resulted in arrest of further accumulation of the substrate and appearance of additional Gaucher cells in affected organs. These data indicate that substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher disease.

  2. Technological innovation strategies for the specific treatment of Chagas disease based on Benznidazole.

    Science.gov (United States)

    Ferraz, Leslie Raphael de Moura; Alves, Alinne Élida Gonçalves; Nascimento, Débora Dolores Souza da Silva; Amariz, Isabela Araújo E; Ferreira, Aline Silva; Costa, Salvana Priscylla Manso; Rolim, Larissa Araújo; Lima, Ádley Antonini Neves de; Rolim Neto, Pedro José

    2018-02-13

    Caused by Trypanosoma cruzi, Chagas disease is responsible for public health problems greater in magnitude than those attributed to malaria, schistosomiasis, or leishmaniasis. A factor in the socioeconomic development of poor countries, Chagas disease can cause death due to a high parasitic burden during its acute phase due and irreversible damage in organs such as the heart, esophagus, and colon during its chronic phase, even when the number of parasites is minimal. For treating Chagas disease, benznidazole (BNZ) remains the drug of choice and, in Latin America, the only drug on the market for treating the disease. However, BNZ has exhibited insufficient activity in the chronic phase of Chagas disease, required administration in large doses, prolonged treatment, and shown a high incidence of adverse reactions (vomiting, rash, peripheral neuropathy, and spinal cord depression), toxicity, and low solubility in water. As an antidote, pharmaceutical technologies have been introduced that can improve BNZ's solubility and dissolution, as well as reduce side effects in light of its bioavailability, all of which can enhance therapy for Chagas disease. In response to that trend, by conducting a literature review, we sought to identify current pharmaceutical technologies used in tandem with BNZ to improve therapy for Chagas disease. Documented techniques include emulsion and microemulsion formation, solutions, parenteral formulas, micronization, and drug delivery systems supported by the development of nanoparticles and cyclodextrins, solid dispersions, and the use of metal-organic frameworks as innovative excipients. Such technologies increase the water solubility of BNZ by 4-25-fold on dissolution and an 85% release with efficacy in only a few minutes, as recorded during a viability experiment with nanoparticle suspensions. That experiment demonstrated the need for a lower concentration of BNZ to kill 50% of trypomastigote forms of T. cruzi, described in terms of the

  3. Comparison of COBAS AMPLICOR Neissefia gonorrhoeae PCR, including confirmation with N-gonorrhoeae-specific 16S rRNA PCR, with traditional culture

    NARCIS (Netherlands)

    Luijt, DS; Bos, PAJ; van Zwet, AA; Vader, PCV; Schirm, J

    A total of 3,023 clinical specimens were tested for Neisseria gonorrhoeae by using COBAS AMPLICOR (CA) PCR and confirmation of positives by N. gonorrhoeae-specific 16S rRNA PCR. The sensitivity of CA plus 16S rRNA PCR was 98.8%, compared to 68.2% for culture. Confirmation of CA positives increased

  4. [Specific features of gastroesophageal reflux disease associated with obesity and overweight].

    Science.gov (United States)

    Livzan, M A; Lapteva, I V; Krolevets, T S; Kiselev, I E

    2016-01-01

    To reveal the specific features of gastroesophageal reflux disease (GERD) associated with obesity and overweight, by investigating the clinical and endoscopic manifestations of the disease, 24-hour pH-metry scores, and leptin levels. A total of 131 patients with GERD were examined. The data about complaints and those from life and medical histories were collected; anthropometric measurements and the results of blood biochemical tests, esophagoduodenoscopy (EPDS), and pH-metry were assessed; and the serum levels of leptin and its receptor were estimated. The patients were allocated into a study group (104 obese and/or overweight patients) and a comparison one (27 normal weight people). Waist circumference, hip circumference, and blood glucose levels proved to be statistically significantly higher in the study group (pstudy group and 5.47 (3.35-7.68) ng/ml in the comparison group; the median levels of the receptors were 18.83 (14.98-25.11) ng/ml and 30.93 (24.68-33.53) ng/ml, respectively). This group showed a moderate negative correlation between these indicators (rs=-0.451; pstudy group displayed higher pH values in the gastric cardia and body (prefluxate having with a low pH value (refluxate having a pH below 4.0 (rs=0.543; preflux episodes longer than 5 minutes in the esophagus, and to the De Meester index for this indicator (rs=0.471; pdisease, which determines the specific features of the disease (alkaline or mixed refluxate) and the need for individualized therapy.

  5. Donor-Specific Anti-HLA Antibodies in Huntington's Disease Recipients of Human Fetal Striatal Grafts.

    Science.gov (United States)

    Porfirio, Berardino; Paganini, Marco; Mazzanti, Benedetta; Bagnoli, Silvia; Bucciantini, Sandra; Ghelli, Elena; Nacmias, Benedetta; Putignano, Anna Laura; Rombolà, Giovanni; Saccardi, Riccardo; Lombardini, Letizia; Di Lorenzo, Nicola; Vannelli, Gabriella B; Gallina, Pasquale

    2015-01-01

    Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence the minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial, which is being carried out at Florence University. All patients had both brain hemispheres grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and posttransplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor specific. Alloimmunization occurred in a time window of 0-49 months after the first neurosurgical procedure. The immunogenic determinants were non-self-epitopes from mismatched HLA antigens. These determinants were both public epitopes shared by two or more HLA molecules and private epitopes unique to individual HLA molecules. One patient had non-donor-specific anti-HLA antibodies in her pretransplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and posttransplant immunogenetic evaluation of patients with intracerebral grafts.

  6. Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

    Science.gov (United States)

    Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

    2016-07-01

    The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Disease-specific structural changes in thalamus and dentatorubrothalamic tract in progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Surova, Yulia; Hall, Sara; Widner, Haakan [Lund University, Department of Clinical Sciences, Lund (Sweden); Skaane University Hospital, Department of Neurology, Lund (Sweden); Nilsson, Markus [Lund University, Lund University Bioimaging Center, Lund (Sweden); Laett, Jimmy [Skaane University Hospital, Center for Medical Imaging and Physiology, Lund (Sweden); Lampinen, Bjoern [Lund University, Department of Medical Radiation Physics, Lund (Sweden); Lindberg, Olof [Malmoe, Lund University, Department of Clinical Sciences, Malmoe (Sweden); Nilsson, Christer [Skaane University Hospital, Department of Neurology, Lund (Sweden); Malmoe, Lund University, Department of Clinical Sciences, Malmoe (Sweden); Westen, Danielle van [Lund University, Department of Clinical Sciences, Lund (Sweden); Skaane University Hospital, Center for Medical Imaging and Physiology, Lund (Sweden); Hansson, Oskar [Malmoe, Lund University, Department of Clinical Sciences, Malmoe (Sweden); Skaane University Hospital, Memory Clinic, Lund (Sweden)

    2015-11-15

    The aim of this study is to identify disease-specific changes of the thalamus, basal ganglia, pons, and midbrain in patients with progressive supranuclear palsy (PSP), Parkinson's disease (PD), and multiple system atrophy with predominant parkinsonism (MSA-P) using diffusion tensor imaging and volumetric analysis. MRI diffusion and volumetric data were acquired in a derivation of 30 controls and 8 patients with PSP and a validation cohort comprised of controls (n = 21) and patients with PSP (n = 27), PD (n = 10), and MSA-P (n = 11). Analysis was performed using regions of interest (ROI), tract-based spatial statistic (TBSS), and tractography and results compared between diagnostic groups. In the derivation cohort, we observed increased mean diffusivity (MD) in the thalamus, superior cerebellar peduncle, and the midbrain in PSP compared to controls. Furthermore, volumetric analysis showed reduced thalamic volumes in PSP. In the validation cohort, the observations of increased MD were replicated by ROI-based analysis and in the thalamus by TBSS-based analysis. Such differences were not found for patients with PD in any of the cohorts. Tractography of the dentatorubrothalamic tract (DRTT) showed increased MD in PSP patients from both cohorts compared to controls and in the validation cohort in PSP compared to PD and MSA patients. Increased MD in the thalamus and along the DRTT correlated with disease stage and motor function in PSP. Patients with PSP, but not PD or MSA-P, exhibit signs of structural abnormalities in the thalamus and in the DRTT. These changes are associated with disease stage and impaired motor function. (orig.)

  8. Disease-specific structural changes in thalamus and dentatorubrothalamic tract in progressive supranuclear palsy

    International Nuclear Information System (INIS)

    Surova, Yulia; Hall, Sara; Widner, Haakan; Nilsson, Markus; Laett, Jimmy; Lampinen, Bjoern; Lindberg, Olof; Nilsson, Christer; Westen, Danielle van; Hansson, Oskar

    2015-01-01

    The aim of this study is to identify disease-specific changes of the thalamus, basal ganglia, pons, and midbrain in patients with progressive supranuclear palsy (PSP), Parkinson's disease (PD), and multiple system atrophy with predominant parkinsonism (MSA-P) using diffusion tensor imaging and volumetric analysis. MRI diffusion and volumetric data were acquired in a derivation of 30 controls and 8 patients with PSP and a validation cohort comprised of controls (n = 21) and patients with PSP (n = 27), PD (n = 10), and MSA-P (n = 11). Analysis was performed using regions of interest (ROI), tract-based spatial statistic (TBSS), and tractography and results compared between diagnostic groups. In the derivation cohort, we observed increased mean diffusivity (MD) in the thalamus, superior cerebellar peduncle, and the midbrain in PSP compared to controls. Furthermore, volumetric analysis showed reduced thalamic volumes in PSP. In the validation cohort, the observations of increased MD were replicated by ROI-based analysis and in the thalamus by TBSS-based analysis. Such differences were not found for patients with PD in any of the cohorts. Tractography of the dentatorubrothalamic tract (DRTT) showed increased MD in PSP patients from both cohorts compared to controls and in the validation cohort in PSP compared to PD and MSA patients. Increased MD in the thalamus and along the DRTT correlated with disease stage and motor function in PSP. Patients with PSP, but not PD or MSA-P, exhibit signs of structural abnormalities in the thalamus and in the DRTT. These changes are associated with disease stage and impaired motor function. (orig.)

  9. Ceramic/polymer nanocomposites with tunable drug delivery capability at specific disease sites.

    Science.gov (United States)

    Liu, Huinan; Webster, Thomas J

    2010-06-01

    Pharmaceutical agents are often used to stimulate new bone formation for the treatment of bone injuries or diseases (such as osteoporosis). However, there are several problems associated with current orthopedic drug delivery methods. First, conventional systemic administration of pharmaceutical agents may not effectively reach targeted sites and, thus, they can cause nonspecific bone formation in areas not affected by injury or disease. Second, even if intentionally delivered or implanted locally to the damaged bone tissue, these agents tend to rapidly diffuse into adjacent tissues due to weak physical bonding to their drug carriers, which limits their potential to promote prolonged bone formation in targeted areas of bone disease. Therefore, in this study, biodegradable ceramic/polymer nanocomposites were explored as novel drug carriers for orthopedic applications to prolong local drug release and, thus, improve drug effectiveness at bone disease sites. Specifically, a bone morphogenetic protein (BMP-7) derived peptide (DIF-7c) was used as a model drug in this study and was first loaded onto nanocrystalline hydroxyapatite (nano-HA) by either covalent chemical attachment or physical adsorption. These drug-carrying nano-HA particles were then dispersed into a degradable polymer (poly-lactide-co-glycolide or PLGA) matrix to create an implantable system capable of long-term drug release. The aminophase silane covalent chemical immobilization process was utilized in this study. These nanocomposite-based drug delivery systems were then characterized for drug loading efficiency and in vitro drug release. Results demonstrated that DIF-7c was successfully immobilized onto nano-HA placed in PLGA. Moreover, a greater prolonged two-phase release profile (of more than 3 months) was achieved when using aminophase silane chemical immobilization to nano-HA particles. Since previous studies have demonstrated greater in vivo bone growth on nano- compared with micron-HA particles

  10. Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies.

    Directory of Open Access Journals (Sweden)

    Ryoko Katagiri

    Full Text Available Although several reports concerning the association of iodine excess and thyroid disease have appeared, no systematic review of the association between iodine excess intake and thyroid diseases, especially hyperthyroidism and hypothyroidism, has yet been reported.We conducted a systematic search of Ovid MEDLINE, PubMed, Cochrane Central Register of Controlled Trials databases, Ichushi-Web and CiNii database for intervention trials and observational studies. Search terms were constructed from related words for excess AND iodine intake or excretion AND thyroid hormones or diseases AND study designs. After considering the qualitative heterogeneity among studies, a meta-analysis was conducted and odds ratios and 95% confidence intervals (CI were estimated in random-effects models. A protocol was registered with PROSPERO (No. CRD42015028081.50 articles were included, including three intervention trials, six case-control studies, six follow-up studies and 35 cross-sectional studies. Three cross-sectional studies in adults included in meta-analysis. Odds ratio of overt and subclinical hypothyroidism between excess and adequate populations were 2.78 (CI:1.47 to 5.27 and 2.03 (CI:1.58 to 2.62 in adults, respectively. Source of excess iodine status was mainly iodized salt or water in included studies.Although universal salt iodization has improved goiter rates, chronic exposure to excess iodine from water or poorly monitored salt are risk factors for hypothyroidism in free-living populations. Monitoring of both iodine concentration in salt as well as the iodine concentration in local drinking water are essential to preventing thyroid diseases. Hypothyroidism should be also carefully monitored in areas with excess iodine. Because of the low quality and limited number of included studies, further evidence and review are required.

  11. Insect-specific irreversible inhibitors of acetylcholinesterase in pests including the bed bug, the eastern yellowjacket, German and American cockroaches, and the confused flour beetle.

    Science.gov (United States)

    Polsinelli, Gregory A; Singh, Sanjay K; Mishra, Rajesh K; Suranyi, Robert; Ragsdale, David W; Pang, Yuan-Ping; Brimijoin, Stephen

    2010-09-06

    Insecticides directed against acetylcholinesterase (AChE) are facing increased resistance among target species as well as increasing concerns for human toxicity. The result has been a resurgence of disease vectors, insects destructive to agriculture, and residential pests. We previously reported a free cysteine (Cys) residue at the entrance to the AChE active site in some insects but not higher vertebrates. We also reported Cys-targeting methanethiosulfonate molecules (AMTSn), which, under conditions that spared human AChE, caused total irreversible inhibition of aphid AChE, 95% inhibition of AChE from the malaria vector mosquito (Anopheles gambia), and >80% inhibition of activity from the yellow fever mosquito (Aedes aegypti) and northern house mosquito (Culex pipiens). We now find the same compounds inhibit AChE from cockroaches (Blattella germanica and Periplaneta americana), the flour beetle (Tribolium confusum), the multi-colored Asian ladybird beetle (Harmonia axyridis), the bed bug (Cimex lectularius), and a wasp (Vespula maculifrons), with IC(50) values of approximately 1-11muM. Our results support further study of Cys-targeting inhibitors as conceptually novel insecticides that may be free of resistance in a range of insect pests and disease vectors and, compared with current compounds, should demonstrate much lower toxicity to mammals, birds, and fish. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Generation of Gene-Engineered Chimeric DNA Molecules for Specific Therapy of Autoimmune Diseases

    Science.gov (United States)

    Gesheva, Vera; Szekeres, Zsuzsanna; Mihaylova, Nikolina; Dimitrova, Iliyana; Nikolova, Maria; Erdei, Anna; Prechl, Jozsef

    2012-01-01

    Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the development of self-reactive B and T cells and autoantibody production. In particular, double-stranded DNA-specific B cells play an important role in lupus progression, and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen. Here, we are exploring, as a new DNA-based therapy of SLE, a chimeric DNA molecule encoding a DNA-mimotope peptide, and the Fv but not the immunogenic Fc fragment of an FcγRIIb-specific monoclonal antibody. This DNA construct was inserted in the expression vector pNut and used as a naked DNA vaccine in a mouse model of lupus. The chimeric DNA molecule can be expressed in eukaryotic cells and cross-links cell surface receptors on DNA-specific B cells, delivering an inhibitory intracellular signal. Intramuscular administration of the recombinant DNA molecule to lupus-prone MRL/lpr mice prevented increase in IgG anti-DNA antibodies and was associated with a low degree of proteinuria, modulation of cytokine profile, and suppression of lupus nephritis. PMID:23075110

  13. Potential of Diffusion Tensor Imaging and Relaxometry for the Detection of Specific Pathological Alterations in Parkinson's Disease (PD.

    Directory of Open Access Journals (Sweden)

    Regina Esterhammer

    Full Text Available The purpose of the present study was to evaluate the potential of multimodal MR imaging including mean diffusivity (MD, fractional anisotropy (FA, relaxation rates R2 and R2* to detect disease specific alterations in Parkinson's Disease (PD. We enrolled 82 PD patients (PD-all with varying disease durations (≤5 years: PD≤5, n = 43; >5 years: PD>5, n = 39 and 38 matched healthy controls (HC, receiving diffusion tensor imaging as well as R2 and R2* relaxometry calculated from multi-echo T2*-weighted and dual-echo TSE imaging, respectively. ROIs were drawn to delineate caudate nucleus (CN, putamen (PU, globus pallidus (GP and substantia nigra (SN on the co-registered maps. The SN was divided in 3 descending levels (SL 1-3. The most significant parameters were used for a flexible discrimination analysis (FDA in a training collective consisting of 25 randomized subjects from each group in order to predict the classification of remaining subjects. PD-all showed significant increases in MD, R2 and R2* within SN and its subregions as well as in MD and R2* within different basal ganglia regions. Compared to the HC group, the PD≤5 and the PD>5 group showed significant MD increases within the SN and its lower two subregions, while the PD≤5 group exhibited significant increases in R2 and R2* within SN and its subregions, and tended to elevation within the basal ganglia. The PD>5 group had significantly increased MD in PU and GP, whereas the PD≤5 group presented normal MD within the basal ganglia. FDA achieved right classification in 84% of study participants. Micro-structural damage affects primarily the SN of PD patients and in later disease stages the basal ganglia. Iron contents of PU, GP and SN are increased at early disease stages of PD.

  14. Detection of infectious bursal disease virus in various lymphoid tissues of experimentally infected specific pathogen free chickens by different reverse transcription polymerase chain reaction assays

    DEFF Research Database (Denmark)

    Kabell, Susanne; Handberg, Kurt; Kusk, Mette

    2005-01-01

    Infectious bursal disease (IBD) is a worldwide distributed immunosuppressive viral disease in young chickens, controlled by vaccination. Emergence of several strains of IBD virus (IBDV) has created a demand for strain-specific diagnostic tools. In the present experiment, five different reverse...... included vaccine strain D78, classical strain Faragher 52/70, and the very virulent Danish strain DK01 The presence of the virus infection was confirmed by histopathologic evaluation of bursa lesions. The largest number of positive samples was obtained with a strain-specific two-step multiplex (MPX) RT...

  15. Predicting spring barley yield from variety-specific yield potential, disease resistance and straw length, and from environment-specific disease loads and weed pressure

    DEFF Research Database (Denmark)

    Østergård, Hanne; Kristensen, Kristian; Pinnschmidt, Hans O.

    2008-01-01

    For low-input crop production, well-characterised varieties increase the possibilities of managing diseases and weeds. This analysis aims at developing a framework for analyzing grain yield using external varietal information about disease resistance, weed competitiveness and yield potential and ...... growth habit. Higher grain yield was thus predicted for taller plants under weed pressure. The results are discussed in relation to the model framework, impact of the considered traits and use of information from conventional variety testing in organic cropping systems....

  16. Specific Radiological Imaging Findings in Patients With Hereditary Pancreatitis During a Long Follow-up of Disease.

    Science.gov (United States)

    van Esch, Aura A J; Drenth, Joost P H; Hermans, John J

    2017-03-01

    Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP. We retrospectively collected data of HP patients with serial imaging and reviewed all radiological imaging studies (transabdominal ultrasonography, computed tomography, and magnetic resonance imaging). We included 15 HP patients, with a mean age of 32.5 years (range, 9-61 years) and mean disease duration of 24.1 years (range, 6-42 years). In total, 152 imaging studies were reviewed. Seventy-three percent of patients had a dilated main pancreatic duct (MPD) (width 3.5-18 mm). The MPD varied in size during disease course, with temporary reduction in diameter after drainage procedures. A severe dilated MPD (>10 mm) often coincided with presence of intraductal calcifications (size, 1-12 mm). In 73% of patients, pancreatic parenchyma atrophy occurred, which did not correlate with presence of exocrine or endocrine insufficiency. In HP, the MPD diameter increases with time, mostly without dilated side branches, and is often accompanied by large intraductal calcifications. The size of the MPD is independent of disease state. Atrophy of pancreatic parenchyma is not correlated with exocrine or endocrine insufficiency.

  17. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    International Nuclear Information System (INIS)

    Mealey, Robert H.; Zhang Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.

    2003-01-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined

  18. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

    DEFF Research Database (Denmark)

    Ellinghaus, David; Jostins, Luke; Spain, Sarah L

    2016-01-01

    We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more th...

  19. Correlation between Asian Dust and Specific Radioactivities of Fission Products Included in Airborne Samples in Tokushima, Shikoku Island, Japan, Due to the Fukushima Nuclear Accident

    Energy Technology Data Exchange (ETDEWEB)

    Sakama, M., E-mail: minorusakama@tokushima-u.ac.jp [Department of Radiological Science, Division of Biomedical Information Sciences, Institute of Health Biosciences, The University of Tokushima, Tokushima 770-8509 (Japan); Nagano, Y. [Department of Radiological Science, Division of Biomedical Information Sciences, Institute of Health Biosciences, The University of Tokushima, Tokushima 770-8509 (Japan); Kitade, T. [Department of Laboratory, M and S Instruments Inc., Osaka 532-0005 (Japan); Shikino, O. [Department of Inorganic Analysis, PerkinElmer Japan Co. Ltd., Yokohama 240-0005 (Japan); Nakayama, S. [Department of Nuclear Science, Institute of Socio-Arts and Sciences, The University of Tokushima, Tokushima 770-8502 (Japan)

    2014-06-15

    Radioactive fission product {sup 131}I released from the Fukushima Daiichi Nuclear Power Plants (FD-NPP) was first detected on March 23, 2011 in an airborne aerosol sample collected at Tokushima, Shikoku Island, located in western Japan. Two other radioactive fission products, {sup 134}Cs and {sup 137}Cs were also observed in a sample collected from April 2 to 4, 2011. The maximum specific radioactivities observed in this work were about 2.5 to 3.5 mBq×m{sup -3} in a airborne aerosol sample collected on April 6. During the course of the continuous monitoring, we also made our first observation of seasonal Asian Dust and those fission products associated with the FDNPP accident concurrently from May 2 to 5, 2011. We found that the specific radioactivities of {sup 134}Cs and {sup 137}Cs decreased drastically only during the period of Asian Dust. And also, it was found that this trend was very similar to the atmospheric elemental concentration (ng×m{sup -3}) variation of stable cesium ({sup 133}Cs) quantified by elemental analyses using our developed ICP-DRC-MS instrument.

  20. Correlation between Asian Dust and Specific Radioactivities of Fission Products Included in Airborne Samples in Tokushima, Shikoku Island, Japan, Due to the Fukushima Nuclear Accident

    International Nuclear Information System (INIS)

    Sakama, M.; Nagano, Y.; Kitade, T.; Shikino, O.; Nakayama, S.

    2014-01-01

    Radioactive fission product 131 I released from the Fukushima Daiichi Nuclear Power Plants (FD-NPP) was first detected on March 23, 2011 in an airborne aerosol sample collected at Tokushima, Shikoku Island, located in western Japan. Two other radioactive fission products, 134 Cs and 137 Cs were also observed in a sample collected from April 2 to 4, 2011. The maximum specific radioactivities observed in this work were about 2.5 to 3.5 mBq×m -3 in a airborne aerosol sample collected on April 6. During the course of the continuous monitoring, we also made our first observation of seasonal Asian Dust and those fission products associated with the FDNPP accident concurrently from May 2 to 5, 2011. We found that the specific radioactivities of 134 Cs and 137 Cs decreased drastically only during the period of Asian Dust. And also, it was found that this trend was very similar to the atmospheric elemental concentration (ng×m -3 ) variation of stable cesium ( 133 Cs) quantified by elemental analyses using our developed ICP-DRC-MS instrument

  1. Clinical significance of fluoroscopic patterns specific for the mitotic spindle in patients with reumatic diseases

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Objective: we proposed to determine the clinical significance of anti-NuMA and anti-HsEg5 antibodies in a group of patients affected with rheumatic diseases. Materials and methods: indirect immunofluorescence on HEp-2000 cells at serum dilution of 1:40 was used to examin 26 sera which had previously showed a “mitotic spindle” fluoroscopic pattern type during laboratory routine. Results: 21 sera (80,7% were identified with NuMA and 5 (19,3% with HsEg5 patterns alone or associated with other ANA patterns. However only patients with isolated positiveness and that is 15 with NuMA and 4 with HsEg5 stainings were included in this study. Of the NuMA positive patients 5 were affected with arthropathies associated to different forms of thyroiditis, 2 with seronegative arthritis, 2 with antiphospholipid syndrome, 1 with systemic lupus erythematosus (SLE, 1 with rheumatoid arthritis, 1 with sicca syndrome, 1 with undifferentiated connective tissue disease, 1 with Mycoplasma pneumaniae infection and 1 with retinal thrombosis. Of the HsEg5 positive patients 3 were affected with SLE and 1 with seronegative arthritis. Conclusions: NuMA does not prevail in any defined rheumatic disease, while HsEg5 staining were more frequent (75% in patients affected with SLE all of whom showing high antibody titres.

  2. Factors associated with disease-specific survival of patients with non-small cell lung cancer.

    Science.gov (United States)

    Souza, Mirian Carvalho de; Cruz, Oswaldo Gonçalves; Vasconcelos, Ana Glória Godoi

    2016-01-01

    Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer. O câncer de pulmão é um problema de saúde pública global e é associado a elevada mortalidade. Ele poderia ser evitado em grande parte com a redução da prevalência do tabagismo. O objetivo deste estudo foi analisar os efeitos de fatores sociais, comportamentais e clínicos sobre o tempo de sobrevida de pacientes com câncer de pulmão de células não pequenas atendidos, entre 2000 e 2003, no Hospital do Câncer I do Instituto Nacional de Câncer José Alencar Gomes da Silva, localizado na

  3. Creating Shape Templates for Patient Specific Biventricular Modeling in Congenital Heart Disease

    Science.gov (United States)

    Gilbert, Kathleen; Farrar, Genevieve; Cowan, Brett R.; Suinesiaputra, Avan; Occleshaw, Christopher; Pontré, Beau; Perry, James; Hegde, Sanjeet; Marsden, Alison; Omens, Jeff; McCulloch, Andrew; Young, Alistair A.

    2018-01-01

    Survival rates for infants with congenital heart disease (CHD) are improving, resulting in a growing population of adults with CHD. However, the analysis of left and right ventricular function is very time-consuming owing to the variety of congenital morphologies. Efficient customization of patient geometry and function depends on high quality shape templates specifically designed for the application. In this paper, we combine a method for creating finite element shape templates with an interactive template customization to patient MRI examinations. This enables different templates to be chosen depending on patient morphology. To demonstrate this pipeline, a new biventricular template with 162 elements was created and tested in place of an existing 82-element template. The method was able to provide fast interactive biventricular analysis with 0.31 sec per edit response time. The new template was customized to 13 CHD patients with similar biventricular topology, showing improved performance over the previous template and good agreement with clinical indices. PMID:26736353

  4. Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

    Directory of Open Access Journals (Sweden)

    Dydensborg Sander S

    2016-12-01

    Full Text Available Stine Dydensborg Sander,1-3 Ketil Størdal,4,5 Tine Plato Hansen,6 Anne-Marie Nybo Andersen,7 Joseph A Murray,8 Søren Thue Lillevang,9 Steffen Husby1,2 1Hans Christian Andersen Children’s Hospital, Odense University Hospital, 2Institute of Clinical Research, University of Southern Denmark, 3Odense Patient Data Explorative Network (OPEN, Odense University Hospital, Odense, Denmark; 4Mental and Physical Health, Norwegian Institute of Public Health, Oslo, 5Department of Pediatrics, Ostfold Hospital Trust, Fredrikstad, Norway; 6Department of Pathology, Hvidovre Hospital, 7Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 8Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 9Department of Clinical Immunology, Odense University Hospital, Odense, Denmark Purpose: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank and information on celiac disease-specific antibodies and human leukocyte antigen (HLA genotypes obtained from patient medical records.Patients and methods: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG and HLA genotypes.Results: We identified 2,247 children who were registered in the Danish National Patient Register with celiac disease. Duodenal biopsies for 1,555 of the children (69% were registered in the Patobank; 1,127 (50% had a biopsy that was compatible with celiac disease (ie, Marsh 2–3. We accessed the medical

  5. Function and modulation of premotor brainstem parasympathetic cardiac neurons that control heart rate by hypoxia-, sleep-, and sleep-related diseases including obstructive sleep apnea.

    Science.gov (United States)

    Dergacheva, Olga; Weigand, Letitia A; Dyavanapalli, Jhansi; Mares, Jacquelyn; Wang, Xin; Mendelowitz, David

    2014-01-01

    Parasympathetic cardiac vagal neurons (CVNs) in the brainstem dominate the control of heart rate. Previous work has determined that these neurons are inherently silent, and their activity is largely determined by synaptic inputs to CVNs that include four major types of synapses that release glutamate, GABA, glycine, or serotonin. Whereas prior reviews have focused on glutamatergic, GABAergic and glycinergic pathways, and the receptors in CVNs activated by these neurotransmitters, this review focuses on the alterations in CVN activity with hypoxia-, sleep-, and sleep-related cardiovascular diseases including obstructive sleep apnea. © 2014 Elsevier B.V. All rights reserved.

  6. Genotype-Specific Minimal Residual Disease Interpretation Improves Stratification in Pediatric Acute Lymphoblastic Leukemia

    Science.gov (United States)

    O’Connor, David; Enshaei, Amir; Bartram, Jack; Hancock, Jeremy; Harrison, Christine J.; Hough, Rachael; Samarasinghe, Sujith; Schwab, Claire; Vora, Ajay; Wade, Rachel; Moppett, John; Moorman, Anthony V.; Goulden, Nick

    2018-01-01

    Purpose Minimal residual disease (MRD) and genetic abnormalities are important risk factors for outcome in acute lymphoblastic leukemia. Current risk algorithms dichotomize MRD data and do not assimilate genetics when assigning MRD risk, which reduces predictive accuracy. The aim of our study was to exploit the full power of MRD by examining it as a continuous variable and to integrate it with genetics. Patients and Methods We used a population-based cohort of 3,113 patients who were treated in UKALL2003, with a median follow-up of 7 years. MRD was evaluated by polymerase chain reaction analysis of Ig/TCR gene rearrangements, and patients were assigned to a genetic subtype on the basis of immunophenotype, cytogenetics, and fluorescence in situ hybridization. To examine response kinetics at the end of induction, we log-transformed the absolute MRD value and examined its distribution across subgroups. Results MRD was log normally distributed at the end of induction. MRD distributions of patients with distinct genetic subtypes were different (P acute lymphoblastic leukemia responded more slowly. The risk of relapse was correlated with MRD kinetics, and each log reduction in disease level reduced the risk by 20% (hazard ratio, 0.80; 95% CI, 0.77 to 0.83; P < .001). Although the risk of relapse was directly proportional to the MRD level within each genetic risk group, absolute relapse rate that was associated with a specific MRD value or category varied significantly by genetic subtype. Integration of genetic subtype–specific MRD values allowed more refined risk group stratification. Conclusion A single threshold for assigning patients to an MRD risk group does not reflect the response kinetics of the different genetic subtypes. Future risk algorithms should integrate genetics with MRD to accurately identify patients with the lowest and highest risk of relapse. PMID:29131699

  7. Disease specific stress of tumor patients at the beginning of radiotherapy. Effect on psychosocial support requirement

    International Nuclear Information System (INIS)

    Sehlen, S.; Hollenhorst, H.; Schymura, B.; Firsching, M.; Duehmke, E.; Herschbach, P.

    2001-01-01

    Purpose: Radiotherapy brings a tumor patient into a special life situation in which different variables play a role of often unknown importance. The goal of this study was to investigate disease specific stress of tumor patients at the beginning of radiotherapy with established psychodiagnostic questionnaires and to evaluate the effect on psychosocial support requirement in order to reduce stress and to improve quality of life and compliance during radiotherapeutical treatment. Patients and Methods: 732 patients were screened, of whom 446 (60.9%) fulfilled the criteria for inclusion (refusals 21.0%, low Karnofsky performance status 6.6%, management problems 3.4%, language barriers 3.0%, cognitive restrictions 2.6%, death 2.5%). Disease specific aspects of stress in the questionnaire (Fragebogen zur Belastung von Krebspatienten, FBK), life situation (LS) and self-defined care requirements (BB) were self-rated by patients with different tumor types before radiotherapy. Medical and sociodemographic data were also documented. We investigated 446 patients (262 male, 184 female; median age 60.0 years) with different diagnoses. Results: Stress was observed mainly due to reduction of efficiency, anxiety and pain on the subscales. Women had a significant higher stress on subscales of pain (p=0.016) and anxiety (p=0.009), patients younger than 45 years in the subscale information (p=0.002) and patients older than 45 and younger than 60 years in the subscale anxiety (p=0.002) and the total score (p=0.003). Patients with mamma carcinoma had the highest stress. The maximum percentages of patients under high stress were found for the subscales of efficiency (43%) and anxiety (40%). The support requirement was characterized by the need of more medical information and dialogue with the doctor. We saw a significant correlation of high stress and high care requirement. Conclusions: Psychosocial support should be founded on psychosocial stress diagnostic and self-defined care

  8. Source-specific fine particulate air pollution and systemic inflammation in ischaemic heart disease patients

    Science.gov (United States)

    Siponen, Taina; Yli-Tuomi, Tarja; Aurela, Minna; Dufva, Hilkka; Hillamo, Risto; Hirvonen, Maija-Riitta; Huttunen, Kati; Pekkanen, Juha; Pennanen, Arto; Salonen, Iiris; Tiittanen, Pekka; Salonen, Raimo O; Lanki, Timo

    2015-01-01

    Objective To compare short-term effects of fine particles (PM2.5; aerodynamic diameter <2.5 µm) from different sources on the blood levels of markers of systemic inflammation. Methods We followed a panel of 52 ischaemic heart disease patients from 15 November 2005 to 21 April 2006 with clinic visits in every second week in the city of Kotka, Finland, and determined nine inflammatory markers from blood samples. In addition, we monitored outdoor air pollution at a fixed site during the study period and conducted a source apportionment of PM2.5 using the Environmental Protection Agency's model EPA PMF 3.0. We then analysed associations between levels of source-specific PM2.5 and markers of systemic inflammation using linear mixed models. Results We identified five source categories: regional and long-range transport (LRT), traffic, biomass combustion, sea salt, and pulp industry. We found most evidence for the relation of air pollution and inflammation in LRT, traffic and biomass combustion; the most relevant inflammation markers were C-reactive protein, interleukin-12 and myeloperoxidase. Sea salt was not positively associated with any of the inflammatory markers. Conclusions Results suggest that PM2.5 from several sources, such as biomass combustion and traffic, are promoters of systemic inflammation, a risk factor for cardiovascular diseases. PMID:25479755

  9. A novel Capsicum gene inhibits host-specific disease resistance to Phytophthora capsici.

    Science.gov (United States)

    Reeves, Gregory; Monroy-Barbosa, Ariadna; Bosland, Paul W

    2013-05-01

    A novel disease resistance inhibitor gene (inhibitor of P. capsici resistance [Ipcr]), found in the chile pepper (Capsicum annuum) variety 'New Mexico Capsicum Accession 10399' (NMCA10399), inhibits resistance to Phytophthora capsici but not to other species of Phytophthora. When a highly P. capsici-resistant variety was hybridized with NMCA10399, the resultant F1 populations, when screened, were completely susceptible to P. capsici for root rot and foliar blight disease syndromes, despite the dominance inheritance of P. capsici resistance in chile pepper. The F2 population displayed a 3:13 resistant-to-susceptible (R:S) ratio. The testcross population displayed a 1:1 R:S ratio, and a backcross population to NMCA10399 displayed complete susceptibility. These results demonstrate the presence of a single dominant inhibitor gene affecting P. capsici resistance in chile pepper. Moreover, when lines carrying the Ipcr gene were challenged against six Phytophthora spp., the nonhost resistance was not overcome. Therefore, the Ipcr gene is interfering with host-specific resistance but not the pathogen- or microbe-associated molecular pattern nonhost responses.

  10. Recombinational DSBs-intersected genes converge on specific disease- and adaptability-related pathways.

    Science.gov (United States)

    Yang, Zhi-Kai; Luo, Hao; Zhang, Yanming; Wang, Baijing; Gao, Feng

    2018-05-03

    The budding yeast Saccharomyces cerevisiae is a model species powerful for studying the recombination of eukaryotes. Although many recombination studies have been performed for this species by experimental methods, the population genomic study based on bioinformatics analyses is urgently needed to greatly increase the range and accuracy of recombination detection. Here, we carry out the population genomic analysis of recombination in S. cerevisiae to reveal the potential rules between recombination and evolution in eukaryotes. By population genomic analysis, we discover significantly more and longer recombination events in clinical strains, which indicates that adverse environmental conditions create an obviously wider range of genetic combination in response to the selective pressure. Based on the analysis of recombinational DSBs-intersected genes (RDIGs), we find that RDIGs significantly converge on specific disease- and adaptability-related pathways, indicating that recombination plays a biologically key role in the repair of DSBs related to diseases and environmental adaptability, especially the human neurological disorders (NDs). By evolutionary analysis of RDIGs, we find that the RDIGs highly prevailing in populations of yeast tend to be more evolutionarily conserved, indicating the accurate repair of DSBs in these RDIGs is critical to ensure the eukaryotic survival or fitness. fgao@tju.edu.cn. Supplementary data are available at Bioinformatics online.

  11. Current approach to the diagnosis of IgG4-related disease - Combination of comprehensive diagnostic and organ-specific criteria.

    Science.gov (United States)

    Umehara, Hisanori; Okazaki, Kazuichi; Nakamura, Takuji; Satoh-Nakamura, Tomomi; Nakajima, Akio; Kawano, Mitsuhiro; Mimori, Tsuneyo; Chiba, Tsutomu

    2017-05-01

    IgG4-related disease (IgG4-RD) is a fascinating clinical entity proposed by Japanese investigators, and includes a wide variety of diseases, formerly diagnosed as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis, retroperitoneal fibrosis, etc. Although all clinicians in every field of medicine may encounter this new disease, a unifying diagnostic criterion has not been established. In 2011, the Japanese IgG4 team, organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan, published comprehensive diagnostic criteria for IgG4-RD. Several problems with these criteria have arisen in clinical practice, however, including the difficulty obtaining biopsy samples from some patients, and the sensitivity and the specificity of techniques used to measure serum IgG4 concentrations. Although serum IgG4 concentration is an important clinical marker for IgG4-RD, its diagnostic utility in differentiating IgG4-RD from other diseases, called IgG4-RD mimickers, remains unclear. This review describes the current optimal approach for the diagnosis of IgG4-RD, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.

  12. Measurement properties of disease-specific questionnaires in patients with neck pain: a systematic review.

    Science.gov (United States)

    Schellingerhout, Jasper M; Verhagen, Arianne P; Heymans, Martijn W; Koes, Bart W; de Vet, Henrica C; Terwee, Caroline B

    2012-05-01

    To critically appraise and compare the measurement properties of the original versions of neck-specific questionnaires. Bibliographic databases were searched for articles concerning the development or evaluation of the measurement properties of an original version of a self-reported questionnaire, evaluating pain and/or disability, which was specifically developed or adapted for patients with neck pain. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using a checklist, specifically designed for evaluating studies on measurement properties. The search strategy resulted in a total of 3,641 unique hits, of which 25 articles, evaluating 8 different questionnaires, were included in our study. The Neck Disability Index is the most frequently evaluated questionnaire and shows positive results for internal consistency, content validity, structural validity, hypothesis testing, and responsiveness, but a negative result for reliability. The other questionnaires show positive results, but the evidence for each measurement property is mostly limited, and at least 50% of the information on measurement properties per questionnaire is lacking. Our findings imply that studies of high methodological quality are needed to properly assess the measurement properties of the currently available questionnaires. Until high quality studies are available, we recommend using these questionnaires with caution. There is no need for the development of new neck-specific questionnaires until the current questionnaires have been adequately assessed.

  13. Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states.

    Science.gov (United States)

    Cunningham, Timothy J; Ford, Earl S; Croft, Janet B; Merrick, Melissa T; Rolle, Italia V; Giles, Wayne H

    2014-01-01

    Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population. Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only. ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

  14. Risk Factors in the Initial Presentation of Specific Cardiovascular Disease Syndromes

    Science.gov (United States)

    2013-03-03

    Heart Diseases; Cardiovascular Diseases; Acute Myocardial Infarction; Unstable Angina; Chronic Stable Angina; Ischemic Stroke; Cerebrovascular Accident; Subarachnoid Hemorrhage; Transient Ischemic Attack; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Sudden Coronary Death; Ventricular Arrhythmia; Sudden Death; Cardiac Arrest; Heart Failure

  15. Early life status epilepticus and stress have distinct and sex-specific effects on learning, subsequent seizure outcomes, including anticonvulsant response to phenobarbital.

    Science.gov (United States)

    Akman, Ozlem; Moshé, Solomon L; Galanopoulou, Aristea S

    2015-02-01

    Neonatal status epilepticus (SE) is often associated with adverse cognitive and epilepsy outcomes. We investigate the effects of three episodes of kainic acid-induced SE (3KA-SE) and maternal separation in immature rats on subsequent learning, seizure susceptibility, and consequences, and the anticonvulsant effects of phenobarbital, according to sex, type, and age at early life (EL) event. 3KA-SE or maternal separation was induced on postnatal days (PN) 4-6 or 14-16. Rats were tested on Barnes maze (PN16-19), or lithium-pilocarpine SE (PN19) or flurothyl seizures (PN32). The anticonvulsant effects of phenobarbital (20 or 40 mg/kg/rat, intraperitoneally) pretreatment were tested on flurothyl seizures. FluoroJadeB staining assessed hippocampal injury. 3KA-SE or separation on PN4-6 caused more transient learning delays in males and did not alter lithium-pilocarpine SE latencies, but aggravated its outcomes in females. Anticonvulsant effects of phenobarbital were preserved and potentiated in specific groups depending on sex, type, and age at EL event. Early life 3KA-SE and maternal separation cause more but transient cognitive deficits in males but aggravate the consequences of subsequent lithium-pilocarpine SE in females. In contrast, on flurothyl seizures, EL events showed either beneficial or no effect, depending on gender, type, and age at EL events. © 2014 John Wiley & Sons Ltd.

  16. Chiropractic treatment including instrument-assisted manipulation for non-specific dizziness and neck pain in community-dwelling older people: a feasibility randomised sham-controlled trial.

    Science.gov (United States)

    Kendall, Julie C; French, Simon D; Hartvigsen, Jan; Azari, Michael F

    2018-01-01

    Dizziness in older people is a risk factor for falls. Neck pain is associated with dizziness and responds favourably to neck manipulation. However, it is unknown if chiropractic intervention including instrument-assisted manipulation of the neck in older people with neck pain can also improve dizziness. This parallel two-arm pilot trial was conducted in Melbourne, Australia over nine months (October 2015 to June 2016). Participants aged 65-85 years, with self-reported chronic neck pain and dizziness, were recruited from the general public through advertisements in local community newspapers and via Facebook. Participants were randomised using a permuted block method to one of two groups: 1) Activator II™-instrument-assisted cervical and thoracic spine manipulation plus a combination of: light massage; mobilisation; range of motion exercises; and home advice about the application of heat, or 2) Sham-Activator II™-instrument-assisted manipulation (set to zero impulse) plus gentle touch of cervical and thoracic spinal regions. Participants were blinded to group allocation. The interventions were delivered weekly for four weeks. Assessments were conducted one week pre- and post-intervention. Clinical outcomes were assessed blindly and included: dizziness (dizziness handicap inventory [DHI]); neck pain (neck disability index [NDI]); self-reported concerns of falling; mood; physical function; and treatment satisfaction. Feasibility outcomes included recruitment rates, compliance with intervention and outcome assessment, study location, success of blinding, costs and harms. Out of 162 enquiries, 24 participants were screened as eligible and randomised to either the chiropractic ( n  = 13) or sham ( n  = 11) intervention group. Compliance was satisfactory with only two participants lost to follow up; thus, post-intervention data for 12 chiropractic intervention and 10 sham intervention participants were analysed. Blinding was similar between groups. Mild harms

  17. Effectiveness of disease-specific self-management education on health outcomes in patients with chronic obstructive pulmonary disease: An updated systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Tao; Tan, Jing-Yu; Xiao, Lily Dongxia; Deng, Renli

    2017-08-01

    To update a previously published systematic review on the effectiveness of self-management education (SME) for patients with chronic obstructive pulmonary disease (COPD). Electronic databases were accessed (from inception to July 2016) to find relevant randomized controlled trials. Studies that compared SME with routine methods of care in COPD patients were retrieved. Both data synthesis and descriptive analysis were used for outcome assessment (e.g. quality of life and healthcare utilization). Twenty-four studies were included. Data synthesis showed better quality of life among COPD patients receiving SME. Significant reductions in COPD-related hospital admissions and emergency department visits were identified in the SME group. SME may positively affect the reduction of COPD patients' emotional distress. No significant reduction in smoking rate and mortality rate was observed between groups. No clear evidence supports the improvement of pulmonary functions, dyspnea, and nutritional status in COPD patients with the use of SME. SME can be a useful strategy to improve quality of life and disease-specific knowledge in patients with COPD. It also reduces respiratory-related hospital admissions and emergency department visits in COPD patients. Inclusion of SME as one of the key components for the comprehensive management of COPD is encouraged. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

    Directory of Open Access Journals (Sweden)

    MILENA B. P. SOARES

    2001-12-01

    Full Text Available Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC, the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.A doença de Chagas constitui um grave problema de saúde pública na América Latina, onde é uma das principais causas de problemas cardíacos. A cardiopatia chagásica crônica (CChC, forma mais grave da doença, manifesta-se em cerca de 25% dos indivíduos infectados pelo Trypanosoma cruzi, e é caracterizada, a nível histopatológico, pela presença de infiltrados

  19. Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

    Science.gov (United States)

    Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

    2017-11-09

    Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

  20. Spontaneous growth in growth hormone deficiency from birth until 7 years of age: development of disease-specific growth curves.

    Science.gov (United States)

    Mayer, M; Schmitt, K; Kapelari, K; Frisch, H; Köstl, G; Voigt, M

    2010-01-01

    Little is known about spontaneous growth of growth hormone (GH)-deficient children during infancy and childhood. Retrospectively, we calculated disease-specific pretreatment percentiles for height, weight, BMI and growth velocity of 113 GH-deficient boys and 41 GH-deficient girls from birth until 7 years of age, by mean and standard deviation. Infants with idiopathic GH deficiency (GHD) grow in disease-specific percentile channels. There is a significant difference in length and weight from birth onward compared to regional reference (pgrowth velocity, despite a wide variance in the first years, so height deficit became more evident with increasing age. GHD is a congenital disease no matter when height deficit becomes clinically evident, because GH-deficient children grow in disease-specific percentile channels with a highly significantly reduced length and weight, which demonstrates that GH is essential for adequate growth in infancy and early childhood. Copyright (c) 2010 S. Karger AG, Basel.

  1. Long-term post-stroke changes include myelin loss, specific deficits in sensory and motor behaviors and complex cognitive impairment detected using active place avoidance.

    Directory of Open Access Journals (Sweden)

    Jin Zhou

    Full Text Available Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1 sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2 complex active place avoidance learning (APA and simple passive avoidance retention (PA. Electroretinogram (ERG, hemispheric loss (infarction, hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001, sensory (p<0.001, beam balance performance (p<0.01 and hindlimb placement behavior (p<0.01. tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05 but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining. No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01 in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and

  2. Molecular property diagnostic suite (MPDS): Development of disease-specific open source web portals for drug discovery.

    Science.gov (United States)

    Nagamani, S; Gaur, A S; Tanneeru, K; Muneeswaran, G; Madugula, S S; Consortium, Mpds; Druzhilovskiy, D; Poroikov, V V; Sastry, G N

    2017-11-01

    Molecular property diagnostic suite (MPDS) is a Galaxy-based open source drug discovery and development platform. MPDS web portals are designed for several diseases, such as tuberculosis, diabetes mellitus, and other metabolic disorders, specifically aimed to evaluate and estimate the drug-likeness of a given molecule. MPDS consists of three modules, namely data libraries, data processing, and data analysis tools which are configured and interconnected to assist drug discovery for specific diseases. The data library module encompasses vast information on chemical space, wherein the MPDS compound library comprises 110.31 million unique molecules generated from public domain databases. Every molecule is assigned with a unique ID and card, which provides complete information for the molecule. Some of the modules in the MPDS are specific to the diseases, while others are non-specific. Importantly, a suitably altered protocol can be effectively generated for another disease-specific MPDS web portal by modifying some of the modules. Thus, the MPDS suite of web portals shows great promise to emerge as disease-specific portals of great value, integrating chemoinformatics, bioinformatics, molecular modelling, and structure- and analogue-based drug discovery approaches.

  3. Multi-modal MRI analysis with disease-specific spatial filtering: initial testing to predict mild cognitive impairment patients who convert to Alzheimer’s disease

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    Kenichi eOishi

    2011-08-01

    Full Text Available Background: Alterations of the gray and white matter have been identified in Alzheimer’s disease (AD by structural MRI and diffusion tensor imaging (DTI. However, whether the combination of these modalities could increase the diagnostic performance is unknown.Methods: Participants included 19 AD patients, 22 amnestic mild cognitive impairment (aMCI patients, and 22 cognitively normal elderly (NC. The aMCI group was further divided into an aMCI-converter group (converted to AD dementia within three years, and an aMCI-stable group who did not convert in this time period. A T1-weighted image, a T2 map, and a DTI of each participant were normalized, and voxel-based comparisons between AD and NC groups were performed. Regions-of-interest, which defined the areas with significant differences between AD and NC, were created for each modality and named disease-specific spatial filters (DSF. Linear discriminant analysis was used to optimize the combination of multiple MRI measurements extracted by DSF to effectively differentiate AD from NC. The resultant DSF and the discriminant function were applied to the aMCI group to investigate the power to differentiate the aMCI-converters from the aMCI-stable patients. Results: The multi-modal approach with AD-specific filters led to a predictive model with an area under the receiver operating characteristic curve (AUC of 0.93, in differentiating aMCI-converters from aMCI-stable patients. This AUC was better than that of a single-contrast-based approach, such as T1-based morphometry or diffusion anisotropy analysis. Conclusion: The multi-modal approach has the potential to increase the value of MRI in predicting conversion from aMCI to AD.

  4. Prediction of disease-related genes based on weighted tissue-specific networks by using DNA methylation.

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    Li, Min; Zhang, Jiayi; Liu, Qing; Wang, Jianxin; Wu, Fang-Xiang

    2014-01-01

    Predicting disease-related genes is one of the most important tasks in bioinformatics and systems biology. With the advances in high-throughput techniques, a large number of protein-protein interactions are available, which make it possible to identify disease-related genes at the network level. However, network-based identification of disease-related genes is still a challenge as the considerable false-positives are still existed in the current available protein interaction networks (PIN). Considering the fact that the majority of genetic disorders tend to manifest only in a single or a few tissues, we constructed tissue-specific networks (TSN) by integrating PIN and tissue-specific data. We further weighed the constructed tissue-specific network (WTSN) by using DNA methylation as it plays an irreplaceable role in the development of complex diseases. A PageRank-based method was developed to identify disease-related genes from the constructed networks. To validate the effectiveness of the proposed method, we constructed PIN, weighted PIN (WPIN), TSN, WTSN for colon cancer and leukemia, respectively. The experimental results on colon cancer and leukemia show that the combination of tissue-specific data and DNA methylation can help to identify disease-related genes more accurately. Moreover, the PageRank-based method was effective to predict disease-related genes on the case studies of colon cancer and leukemia. Tissue-specific data and DNA methylation are two important factors to the study of human diseases. The same method implemented on the WTSN can achieve better results compared to those being implemented on original PIN, WPIN, or TSN. The PageRank-based method outperforms degree centrality-based method for identifying disease-related genes from WTSN.

  5. Discovery of temporal and disease association patterns in condition-specific hospital utilization rates.

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    Julian S Haimovich

    Full Text Available Identifying temporal variation in hospitalization rates may provide insights about disease patterns and thereby inform research, policy, and clinical care. However, the majority of medical conditions have not been studied for their potential seasonal variation. The objective of this study was to apply a data-driven approach to characterize temporal variation in condition-specific hospitalizations. Using a dataset of 34 million inpatient discharges gathered from hospitals in New York State from 2008-2011, we grouped all discharges into 263 clinical conditions based on the principal discharge diagnosis using Clinical Classification Software in order to mitigate the limitation that administrative claims data reflect clinical conditions to varying specificity. After applying Seasonal-Trend Decomposition by LOESS, we estimated the periodicity of the seasonal component using spectral analysis and applied harmonic regression to calculate the amplitude and phase of the condition's seasonal utilization pattern. We also introduced four new indices of temporal variation: mean oscillation width, seasonal coefficient, trend coefficient, and linearity of the trend. Finally, K-means clustering was used to group conditions across these four indices to identify common temporal variation patterns. Of all 263 clinical conditions considered, 164 demonstrated statistically significant seasonality. Notably, we identified conditions for which seasonal variation has not been previously described such as ovarian cancer, tuberculosis, and schizophrenia. Clustering analysis yielded three distinct groups of conditions based on multiple measures of seasonal variation. Our study was limited to New York State and results may not directly apply to other regions with distinct climates and health burden. A substantial proportion of medical conditions, larger than previously described, exhibit seasonal variation in hospital utilization. Moreover, the application of clustering

  6. Frequency specific activity in subthalamic nucleus correlates with hand bradykinesia in Parkinson's disease.

    Science.gov (United States)

    Tan, Huiling; Pogosyan, Alek; Anzak, Anam; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Ashkan, Keyoumars; Bogdanovic, Marko; Green, Alexander L; Aziz, Tipu; Brown, Peter

    2013-02-01

    Local field potential recordings made from the basal ganglia of patients undergoing deep brain stimulation have suggested that frequency specific activity is involved in determining the rate of force development and the peak force at the outset of a movement. However, the extent to which the basal ganglia might be involved in motor performance later on in a sustained contraction is less clear. We therefore recorded from the subthalamic nucleus region (STNr) in patients with Parkinson's disease (PD) as they made maximal voluntary grips. Relative to age-matched controls they had more rapid force decrement when contraction was meant to be sustained and prolonged release reaction time and slower rate of force offset when they were supposed to release the grip. These impairments were independent from medication status. Increased STNr power over 5-12 Hz (in the theta/alpha band) independently predicted better performance-reduced force decrement, shortened release reaction time and faster rate of force offset. In contrast, lower mean levels and progressive reduction of STNr power over 55-375 Hz (high gamma/high frequency) over the period when contraction was meant to be sustained were both strongly associated with greater force decrement over time. Higher power over 13-23 Hz (low beta) was associated with more rapid force decrement during the period when grip should have been sustained, and with a paradoxical shortening of the release reaction time. These observations suggest that STNr activities at 5-12 Hz and 55-375 Hz are necessary for optimal grip performance and that deficiencies of such activities lead to motor impairments. In contrast, increased levels of 13-25 Hz activity both promote force decrement and shorten the release reaction time, consistent with a role in antagonising (and terminating) voluntary movement. Frequency specific oscillatory activities in the STNr impact on motor performance from the beginning to the end of a voluntary grip. Copyright © 2012

  7. Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson’s Disease Patients

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    Seyed-Mohammad Fereshtehnejad

    2014-01-01

    Full Text Available The impact of Parkinson’s disease (PD on psychological status and quality of life (QoL may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3 (SD=10.4 yr were recruited in this study. PD patients with the onset age of ≤50 yr were defined as “early-onset” (EOPD group (n=45, while the ones with >50 yr at the time of diagnosis were categorized as the “typical-onset” (TOPD patients (n=95. Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale, FSS (fatigue severity scale, MNA (mininutritional assessment, and the UPDRS. Depression score was significantly higher in EOPD group (6.3 (SD=4.5 versus 4.5 (SD=4.2, P=0.02. Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 (SD=21.6 versus 24.4 (SD=22.7, P=0.05. Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients.

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

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    Mario U Manto

    2015-03-01

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

  9. Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease.

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    Parra, Mario A; Sala, Sergio Della; Abrahams, Sharon; Logie, Robert H; Méndez, Luis Guillermo; Lopera, Francisco

    2011-06-01

    Short-term memory binding of visual features which are processed across different dimensions (shape-colour) is impaired in sporadic Alzheimer's disease, familial Alzheimer's disease, and in asymptomatic carriers of familial Alzheimer's disease. This study investigated whether Alzheimer's disease also impacts on within-dimension binding processes. The study specifically explored whether visual short-term memory binding of features of the same type (colour-colour) is sensitive to Alzheimer's disease. We used a neuropsychological battery and a short-term memory binding task to assess patients with sporadic Alzheimer's disease (Experiment 1), familial Alzheimer's disease (Experiment 2) due to the mutation E280A of the Presenilin-1 gene and asymptomatic carriers of the mutation. The binding task assessed change detection within arrays of unicoloured objects (Colour Only) or bicoloured objects the colours of which had to be remembered separately (Unbound Colours) or together (Bound Colours). Performance on the Bound Colours condition (1) explained the largest proportion of variance between patients (sporadic and familial Alzheimer's disease), (2) combined more sensitivity and specificity for the disease than other more traditional neuropsychological tasks, (3) identified asymptomatic carriers of the mutation even when traditional neuropsychological measures and other measures of short-term memory did not and, (4) contrary to shape-colour binding, correlated with measures of hippocampal functions. Colour-colour binding and shape-colour binding both appear to be sensitive to AD even though they seem to rely on different brain mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Hospital specific factors affect quality of blood pressure treatment in chronic kidney disease

    NARCIS (Netherlands)

    Zuilen, A.D. van; Blankestijn, P.J.; Buren, M. van; Dam, M.A. ten; Kaasjager, K.A.; Ligtenberg, G.; Sijpkens, Y.W.; Sluiter, H.E.; Ven, P.J. van der; Vervoort, G.M.M.; Vleming, L.; Bots, M.L.; Wetzels, J.F.M.

    2011-01-01

    BACKGROUND: Blood pressure (BP) is the most important modifiable risk factor for cardiovascular (CV) disease and progression of kidney dysfunction in patients with chronic kidney disease. Despite extensive antihypertensive treatment possibilities, adequate control is notoriously hard to achieve.

  11. Specific reduction of calcium-binding protein (28-kilodalton calbindin-D) gene expression in aging and neurodegenerative diseases

    International Nuclear Information System (INIS)

    Iacopino, A.M.; Christakos, S.

    1990-01-01

    The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases in calbindin·mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. These findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases

  12. PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation.

    Science.gov (United States)

    Tang, Haiming; Thomas, Paul D

    2016-07-15

    PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. Several previous variant pathogenicity prediction methods have been proposed that quantify evolutionary conservation among homologous proteins from different organisms. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors. Here, we describe the PSEP tool, and assess its performance on standard benchmarks for distinguishing disease-associated from neutral variation in humans. On these benchmarks, PSEP outperforms not only previous tools that utilize evolutionary conservation, but also several highly used tools that include multiple other sources of information as well. For predicting pathogenic human variants, the trace back of course starts with a human 'reference' protein sequence, but the PSEP tool can also be applied to predicting deleterious or pathogenic variants in reference proteins from any of the ∼100 other species in the PANTHER database. PANTHER-PSEP is freely available on the web at http://pantherdb.org/tools/csnpScoreForm.jsp Users can also download the command-line based tool at ftp://ftp.pantherdb.org/cSNP_analysis/PSEP/ CONTACT: pdthomas@usc.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model.

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-08-03

    Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015-2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All

  14. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-01-01

    Objectives Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Methods Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015–2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. Findings The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. Conclusions The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. PMID:28775179

  15. Generation of healthy mice from gene-corrected disease-specific induced pluripotent stem cells.

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    Guangming Wu

    2011-07-01

    Full Text Available Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH⁻/⁻ mice as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH⁻/⁻-induced pluripotent stem cells (iPS cells as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH⁻/⁻ iPS cell lines, we aggregated FAH⁻/⁻-iPS cells with tetraploid embryos and obtained entirely FAH⁻/⁻-iPS cell-derived mice that were viable and exhibited the phenotype of the founding FAH⁻/⁻ mice. Then, we transduced FAH cDNA into the FAH⁻/⁻-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell-derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl-1,3-cyclohexanedione. Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models.

  16. Determination of specificity and pattern of antinuclear antibodies (ana) in systemic rheumatic disease patients positive for ana testing

    International Nuclear Information System (INIS)

    Nawaz, H.; Bashir, M.M.; Iqbal, W.

    2018-01-01

    To determine probability of finding antinuclear antibodies (ANA) and anti extractable nuclear antigens (ENA) positive samples and associating ANA patterns with anti-ENA reactivities among a consecutive cohort of samples of systemic rheumatic disease patients referred for ANA testing. Study Design:Prospective cohort study. Place and Duration of Study:Immunology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to June 2016. Methodology:All the samples referred for ANA testing with clinical suspicion of systemic rheumatic disease were included. After screening, ANA positive samples were subjected to anti-ENA antibodies testing (including anti-SSA, anti-SSB, anti-Sm, anti-RNP, anti-SCL-70 and anti-Jo-1 antibodies) and ANA pattern and titer determination. Results:Of 4,347 samples received, 397 were positive for ANA (9%). Of 397, 96 (24%) samples positive on ENA screen were tested for anti-ENA reactivity. Anti-SSA antibodies were found in 59 samples. Commonest ANA patterns were coarse and fine speckled (43 and 22 samples of 81 tested), while majority of samples carried ANA in titers of 1:40 and 1:80 (22 and 18 samples of 81 tested). No specific ANA pattern was associated with any particular anti-ENA reactivity. Conclusion:Among samples/patients referred for investigations of autoimmune disorders, probability of finding positive ANA is approximately 9%. Of these 9%, about 24% also show reactivity against ENA. Commonest ANA pattern is coarse speckled and majority of such patients carry ANA in titers ranging from 1:40 to 1:80. Commonest ENA reactivity was against SSA. (author)

  17. Specific proof of various stages of Osler's disease of the brain via high field magnetic resonance tomography (1. 5 Tesla)

    Energy Technology Data Exchange (ETDEWEB)

    Billet, F; Bluemm, R G; Beyer, H K

    1988-08-01

    MR is a sensitive noninvasive examination method for diagnosing parenchymatous cryptic arteriovenous malformations and sequels of cerebral haemorrhage. In a patient with recurring nosebleed and brain stem syndrome eleven so-called cryptic arteriovenous malformations or their haemorrhage sequels were diagnosed via magnetic resonance tomography. Basing on these specific findings, nosebleeding, and a positive family anamnesis, the findings could be classified as belonging to manifestations of Osler's disease (hereditary haemorrhagic telangiectasia). This rare disease is characterised by a triad of signs: telangiectasias, recurring bleeding, and heredity. In this article the specific MR image is compared with the CT pattern and the results are discussed against the background of literature on Osler's disease which is also known as Rendu-Osler-Weber disease.

  18. DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including those with a low disease burden.

    Science.gov (United States)

    Dun, Karen A; Riley, Louise A; Diano, Giuseppe; Adams, Leanne B; Chiu, Eleanor; Sharma, Archna

    2018-05-01

    Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies. Here, we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease. © 2018 Wiley Periodicals, Inc.

  19. Targeting synaptic dysfunction in Alzheimer's disease by administering a specific nutrient combination.

    Science.gov (United States)

    van Wijk, Nick; Broersen, Laus M; de Wilde, Martijn C; Hageman, Robert J J; Groenendijk, Martine; Sijben, John W C; Kamphuis, Patrick J G H

    2014-01-01

    Synapse loss and synaptic dysfunction are pathological processes already involved in the early stages of Alzheimer's disease (AD). Synapses consist principally of neuronal membranes, and the neuronal and synaptic losses observed in AD have been linked to the degeneration and altered composition and structure of these membranes. Consequently, synapse loss and membrane-related pathology provide viable targets for intervention in AD. The specific nutrient combination Fortasyn Connect (FC) is designed to ameliorate synapse loss and synaptic dysfunction in AD by addressing distinct nutritional needs believed to be present in these patients. This nutrient combination comprises uridine, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium, and is present in Souvenaid, a medical food intended for use in early AD. It has been hypothesized that FC counteracts synaptic loss and reduces membrane-related pathology in AD by providing nutritional precursors and cofactors that act together to support neuronal membrane formation and function. Preclinical studies formed the basis of this hypothesis which is being validated in a broad clinical study program investigating the potential of this nutrient combination in AD. Memory dysfunction is one key early manifestation in AD and is associated with synapse loss. The clinical studies to date show that the FC-containing medical food improves memory function and preserves functional brain network organization in mild AD compared with controls, supporting the hypothesis that this intervention counteracts synaptic dysfunction. This review provides a comprehensive overview of basic scientific studies that led to the creation of FC and of its effects in various preclinical models.

  20. Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin.

    Directory of Open Access Journals (Sweden)

    Melissa K Boles

    2009-12-01

    Full Text Available An accurate and precisely annotated genome assembly is a fundamental requirement for functional genomic analysis. Here, the complete DNA sequence and gene annotation of mouse Chromosome 11 was used to test the efficacy of large-scale sequencing for mutation identification. We re-sequenced the 14,000 annotated exons and boundaries from over 900 genes in 41 recessive mutant mouse lines that were isolated in an N-ethyl-N-nitrosourea (ENU mutation screen targeted to mouse Chromosome 11. Fifty-nine sequence variants were identified in 55 genes from 31 mutant lines. 39% of the lesions lie in coding sequences and create primarily missense mutations. The other 61% lie in noncoding regions, many of them in highly conserved sequences. A lesion in the perinatal lethal line l11Jus13 alters a consensus splice site of nucleoredoxin (Nxn, inserting 10 amino acids into the resulting protein. We conclude that point mutations can be accurately and sensitively recovered by large-scale sequencing, and that conserved noncoding regions should be included for disease mutation identification. Only seven of the candidate genes we report have been previously targeted by mutation in mice or rats, showing that despite ongoing efforts to functionally annotate genes in the mammalian genome, an enormous gap remains between phenotype and function. Our data show that the classical positional mapping approach of disease mutation identification can be extended to large target regions using high-throughput sequencing.

  1. Disease-specific survival in de novo metastatic renal cell carcinoma in the cytokine and targeted therapy era.

    Directory of Open Access Journals (Sweden)

    Sumanta K Pal

    Full Text Available Recent phase III studies of targeted agents for metastatic renal cell carcinoma (mRCC have generated median survival estimates that far exceed those observed during the cytokine era. However, substantial population-based data does not exist to confirm this trend. We sought to determine whether survival has improved for patients with mRCC diagnosed in the era of targeted therapies, as compared to the era of immunotherapy.The Surveillance, Epidemiology, and End Results (SEER Registry was used to identify patients aged 18 and older diagnosed stage IV RCC between 1992 and 2009. Patients had documented clear cell, papillary or chromophobe histology. The Kaplan Meier method and log-rank test were used to compare disease-specific survival (DSS for patients diagnosed from 1992-2004 (i.e., the cytokine era and 2005-2009 (i.e., the targeted therapy era. Univariate and multivariate analyses of relevant clinicopathologic characteristics were also performed.Of 5,176 patients identified using the above characteristics, 2,392 patients were diagnosed from 1992-2004 and 2,784 from 2005-2009. Median DSS was improved in those patients diagnosed from 2005-2009 (16 months vs 13 months; P<0.0001. A similar temporal trend towards improving survival was noted in patients with clear cell (P = 0.0006, but not in patients with non-clear cell disease (P = 0.32. Notable findings on multivariate analysis include an association between shorter DSS and the following characteristics: (1 diagnosis from 1992-2004, (2 advanced age (80+, and (3 absence of cytoreductive nephrectomy.These data reflect progress in the management of mRCC, specifically in the era of targeted therapies. Notably, it was inferred that certain treatment strategies were employed during pre-specified time periods, representing a major caveat of the current analysis. Further studies related to the influence of age and race/ethnicity are warranted, as are studies exploring the role of cytoreductive nephrectomy

  2. Induction of an antigen specific gut inflammatory reaction in mice and rats: a model for human Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Gerlinde Agate Platais Brasil Teixeira

    2009-06-01

    Full Text Available Food allergy is an adverse reaction that occurs in susceptible people when they eat sensitizing foods and is one of the causes of Inflammatory Bowel Disease (IBD. The effort to understand the induction process of these diseases is important as IBD is increasing worldwide, including in Brazil. The aim of this study was to develop an experimental antigen specific inflammatory process of the gut of mice and rats, using peanut seeds. Animals were immunized with peanut protein extract before their exposure to the in natura peanut seeds. Results showed that systemic immunization with peanut protein extracts rendered significantly higher antibody titers than control groups and that immunized animals submitted to a challenge diet containing peanuts presented time dependent alterations of the gut similar to celiac disease. In conclusion, results suggested that this experimental model was a convenient tool to study the evolution of alterations in chronic antigen specific gut inflammatory process.A alergia alimentar consiste em uma reação adversa que ocorre em pessoas susceptíveis quando ingerem alimentos sensibilizantes, sendo uma das causas das Doenças Inflamatórias Intestinais (IBD. O objetivo deste estudo foi desenvolver um protocolo experimental de indução de um processo inflamatório intestinal antígeno-específico em camundongos e ratos. Foi escolhida para a indução deste processo a semente de amendoim. Os animais foram imunizados com o extrato protéico previamente à exposição com a semente in natura. Nossos resultados mostram que a imunização sistêmica com extratos protéicos de amendoim ocasiona títulos significativamente maiores de anticorpos quando comparado ao grupo controle e que os animais imunizados submetidos ao desafio com a dieta contendo exclusivamente amendoim apresentam alterações intestinais tempo-dependente similares àquelas observadas na doença celíaca. Os resultados obtidos sugerem que este modelo

  3. Discriminative and predictive properties of disease-specific and generic health status indexes in elderly COPD patients

    Directory of Open Access Journals (Sweden)

    Forastiere Francesco

    2008-08-01

    Full Text Available Abstract Background The association between bronchial obstruction severity and mortality in Chronic Obstructive Pulmonary Disease (COPD is well established, but it is unknown whether disease-specific health status measures and multidimensional assessment (MDA have comparable prognostic value. Methods We analyzed data coming from the Salute Respiratoria nell'Anziano (Respiratory Health in the Elderly – SaRA study, enrolling elderly people attending outpatient clinics for respiratory and non-respiratory problems. From this population we selected 449 patients with bronchial obstruction (77.3% men, mean age 73.1. We classified patients' health status using tertiles of the Saint George Respiratory Questionnaire (SGRQ and a MDA including functional (the 6' walking test, WT, cognitive (Mini-Mental State Examination, MMSE and affective status (Geriatric Depression Scale, GDS. The agreement of the classification methods was calculated using the kappa statistic, and survival associated with group membership was evaluated using survival analysis. Results Pulmonary function, expressed by the FEV1, worsened with increasing SGRQ or MDA scores. Cognitive function was not associated with the SGRQ, while physical performance and mood status were impaired only in the highest tertile of SGRQ. A poor agreement was found between the two classification systems tested (k = 0.194. Compared to people in the first tertile of SGRQ score, those in the second tertile had a sex-adjusted HR of 1.22 (0.75 – 1.98 and those in the third tertile of 2.90 (1.92 – 4.40. The corresponding figures of the MDA were 1.49 (95% CI 1.02 – 2.18 and 2.01 (95% CI: 1.31 – 3.08. After adjustment for severity of obstruction, only a SGRQ in the upper tertile was associated with mortality (HR: 1.86; 95% CI: 1.14 – 3.02. Conclusion In elderly outpatients with mild-moderate COPD, a disease-specific health status index seems to be a better predictor of death compared to a MDA.

  4. Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes

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    Kent Imaizumi

    2015-12-01

    Full Text Available The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P and dorsoventral (D-V axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS and Alzheimer’s disease (AD by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.

  5. Generic versus Disease-Specific Instruments in Quality-of-life Assessment of Chronic Obstructive Pulmonary Disease

    Czech Academy of Sciences Publication Activity Database

    Malý, Marek; Vondra, V.

    2006-01-01

    Roč. 45, č. 2 (2006), s. 211-215 ISSN 0026-1270 Source of funding: V - iné verejné zdroje Keywords : health-related quality of life * questionnaires * chronic obstructive pulmonary disease * reproducibility * responsiveness Subject RIV: FC - Pulmology Impact factor: 1.684, year: 2006

  6. The specific features of the diagnosis and treatment of coronary heart disease in rheumatoid arthritis (Results of the authors’ studies

    Directory of Open Access Journals (Sweden)

    Natalya Anatolyevna Khramtsova

    2012-01-01

    Full Text Available Coronary heart disease (CHD and its complications occupy the leading place in the pattern of the causes of untimely death in rheumatoid arthritis (RA. Objective: to study the incidence, pattern, and specific features of CHD in patients with RA. Patients and methods. An analytical cross-sectional study was conducted in 257 patients with RA (ARA, 1987. The patients’ mean age was 55.4±11.6 years; RA duration was 14.7years (range 2—20 years. Results. The incidence of CHD in RA was as much as 45.9% (n = 118, including 52.5% (n = 62 for typical angina pectoris on exertion; 25.4% (n = 30 and 22.1% (n = 26 for silent ischemia and arrhythmias, respectively. A high proportion of vertebrogenic cardialgias (48.8%; n = 100 were noted in those who complained of heart pain. The authors identified traditional risk factors, such as hypertension (OR = 12.1, smoking (OR = 10.2, early menopause (OR = 3.6, decreased glomerular filtration rate (OR = 3.5, cardiovascular heredity (OR = 3.1, overweight (OR = 2.5, a heart rate of more than 70 beats/min (OR = 2.3, atherogenic dyslipidemia (OR = 2.3, hyperglycemia (OR = 2.1, and age (OR = 1.7. Along with those, the authors also ascertained CHD predictors associating with chronic inflammation consequences: use of glucocorticoids (OR = 5.0, concomitant anemia as a common complication of RA (OR = 4.7, high DAS 28 scores (OR = 3.7, visual analog scale pain scores of > 50 mm (OR = 2.6, and RA duration of >10 years (OR = 2.2. Conclusion. The specific features of CHD in RA include the frequent detection of arrhythmias and silent ischemia. The importance of the degree of inflammatory activity along with the traditional risk factors of CHD is apparent.

  7. Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

    Science.gov (United States)

    Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

    2017-12-01

    Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key

  8. Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

    Directory of Open Access Journals (Sweden)

    Wan Li

    Full Text Available The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial. Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

  9. Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease.

    Science.gov (United States)

    Bloom, Seth M; Bijanki, Vinieth N; Nava, Gerardo M; Sun, Lulu; Malvin, Nicole P; Donermeyer, David L; Dunne, W Michael; Allen, Paul M; Stappenbeck, Thaddeus S

    2011-05-19

    The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here, we fulfilled Koch's postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively reisolated them in culture. The bacteria colonized IBD-susceptible and -nonsusceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease, but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease

    Science.gov (United States)

    Bloom, Seth M.; Bijanki, Vinieth N.; Nava, Gerardo M.; Sun, Lulu; Malvin, Nicole P.; Donermeyer, David L.; Dunne, W. Michael; Allen, Paul M.; Stappenbeck, Thaddeus S.

    2011-01-01

    SUMMARY The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here we fulfilled Koch’s postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively re-isolated them in culture. The bacteria colonized IBD-susceptible and non-susceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD. PMID:21575910

  11. Attributing the human disease burden of foodborne infections to specific sources.

    NARCIS (Netherlands)

    Pires, S.M.; Evers, E.G.; van Pelt, W.; Ayers, T.; Scallan, E.; Angulo, F.J.; Havelaar, A.H.; Hald, T.

    2009-01-01

    Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However, information

  12. Attributing the Human Disease Burden of Foodborne Infections to Specific Sources

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Evers, Eric E.; Van Pely, Wilfrid

    2009-01-01

    Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However...

  13. Field Note: A Disease Specific Expert System for the Indian Mango Crop

    Science.gov (United States)

    Chakrabarti, Dilip Kumar; Chakraborty, Pinaki

    2007-01-01

    Mango ("Mangifera indica") is a popular fruit and an important cash crop of southeast Asia. The mango malformation disease has been responsible for the degraded yield of the crop now for a long time (Kumar and Chakrabarti, 1997). The disease is difficult to cure and often takes the shape of an epidemic. Though much study has been done…

  14. Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries

    Science.gov (United States)

    Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H.

    2014-01-01

    Background Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies. Aims of the Study The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Methods and Findings Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (ptoxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. Conclusions The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more

  15. Toxoplasmosis--a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries.

    Science.gov (United States)

    Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H

    2014-01-01

    Toxoplasmosis is becoming a global health hazard as it infects 30-50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this 'asymptomatic infection' may also lead to development of other human pathologies. The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Prevalence data published between 1995-2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (ptoxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and

  16. Sensitivity and specificity of thallium-201 perfusion scintigrams under exercise in the diagnosis of coronary artery disease

    International Nuclear Information System (INIS)

    Verani, M.S.; Marcus, M.L.; Razzak, M.A.; Ehrhardt, J.C.

    1978-01-01

    The specificity and sensitivity of thallium-201 myocardial perfusion imaging (MPI), under exercise, in patients with suspected coronary-obstructive disease was compared with graded exercise ECG tests (GTX) in patients with angiographically normal (N = 34) and obstructed (N = 48) coronary arteries. Of the 34 patients with normal coronaries, only one had a perfusion defect on the MPI (specificity 97%). Of the 48 patients with coronary obstructive disease (>50% obstruction of at least one coronary vessel), MPI was positive in 38 (sensitivity 79%). In contrast, the GTX had a specificity of 62% and sensitivity of 88% if nondiagnostic GTX tests are excluded. When the MPI and the GTX were used in combination, however, the sensitivity of detecting patients with coronary obstructive disease was increased to 94% (p < 0.01). The MPI was particularly useful in the evaluation of the 26 patients with nondiagnostic GTX. In this group, 24 of the 26 patients were correctly identified by the MPI with respect to the presence or absence of coronary-obstructive disease. In the 14 patients with a history of classical angina but with normal coronaries, the MPI was negative in 13 and positive in one, thus suggesting that in the majority of these patients transient transmural myocardial ischemia probably does not occur during exercise. The presence or absence of angiographically demonstrable coronary collateral vessels did not seem to influence the exercise MPI in patients with coronary-obstructive disease. Thus, although the MPI does not correctly identify all patients with either coronary-obstructive disease or normal coronary arteries, it is helpful in patients who have a nondiagnostic GTX. Furthermore, when used in combination with the GTX, the MPI significantly increases the likelihood that significant coronary-obstructive disease is present when both tests are positive, and that coronary disease is absent when both tests are negative

  17. Development of an Automated MRI-Based Diagnostic Protocol for Amyotrophic Lateral Sclerosis Using Disease-Specific Pathognomonic Features: A Quantitative Disease-State Classification Study.

    Science.gov (United States)

    Schuster, Christina; Hardiman, Orla; Bede, Peter

    2016-01-01

    Despite significant advances in quantitative neuroimaging, the diagnosis of ALS remains clinical and MRI-based biomarkers are not currently used to aid the diagnosis. The objective of this study is to develop a robust, disease-specific, multimodal classification protocol and validate its diagnostic accuracy in independent, early-stage and follow-up data sets. 147 participants (81 ALS patients and 66 healthy controls) were divided into a training sample and a validation sample. Patients in the validation sample underwent follow-up imaging longitudinally. After removing age-related variability, indices of grey and white matter integrity in ALS-specific pathognomonic brain regions were included in a cross-validated binary logistic regression model to determine the probability of individual scans indicating ALS. The following anatomical regions were assessed for diagnostic classification: average grey matter density of the left and right precentral gyrus, the average fractional anisotropy and radial diffusivity of the left and right superior corona radiata, inferior corona radiata, internal capsule, mesencephalic crus of the cerebral peduncles, pontine segment of the corticospinal tract, and the average diffusivity values of the genu, corpus and splenium of the corpus callosum. Using a 50% probability cut-off value of suffering from ALS, the model was able to discriminate ALS patients and HC with good sensitivity (80.0%) and moderate accuracy (70.0%) in the training sample and superior sensitivity (85.7%) and accuracy (78.4%) in the independent validation sample. This diagnostic classification study endeavours to advance ALS biomarker research towards pragmatic clinical applications by providing an approach of automated individual-data interpretation based on group-level observations.

  18. Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases.

    Science.gov (United States)

    Elnady, Basant M; Kamal, Naglaa M; Shaker, Raneyah H M; Soliman, Amal F; Hasan, Waleed A; Alghamdi, Hamed A; Algethami, Mohammed M; Jajah, Mohamed Bilal

    2016-09-01

    Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus

  19. Microglia Responses in Acute and Chronic Neurological Diseases: What Microglia-Specific Transcriptomic Studies Taught (and did Not Teach Us

    Directory of Open Access Journals (Sweden)

    Hélène E. Hirbec

    2017-07-01

    Full Text Available Over the last decade, microglia have been acknowledged to be key players in central nervous system (CNS under both physiological and pathological conditions. They constantly survey the CNS environment and as immune cells, in pathological contexts, they provide the first host defense and orchestrate the immune response. It is well recognized that under pathological conditions microglia have both sequential and simultaneous, beneficial and detrimental effects. Cell-specific transcriptomics recently became popular in Neuroscience field allowing concurrent monitoring of the expression of numerous genes in a given cell population. Moreover, by comparing two or more conditions, these approaches permit to unbiasedly identify deregulated genes and pathways. A growing number of studies have thus investigated microglial transcriptome remodeling over the course of neuropathological conditions and highlighted the molecular diversity of microglial response to different diseases. In the present work, we restrict our review to microglia obtained directly from in vivo samples and not cell culture, and to studies using whole-genome strategies. We first critically review the different methods developed to decipher microglia transcriptome. In particular, we compare advantages and drawbacks of flow cytometry and laser microdissection to isolate pure microglia population as well as identification of deregulated microglial genes obtained via RNA sequencing (RNA-Seq vs. microarrays approaches. Second, we summarize insights obtained from microglia transcriptomes in traumatic brain and spinal cord injuries, pain and more chronic neurological conditions including Amyotrophic lateral sclerosis (ALS, Alzheimer disease (AD and Multiple sclerosis (MS. Transcriptomic responses of microglia in other non-neurodegenerative CNS disorders such as gliomas and sepsis are also addressed. Third, we present a comparison of the most activated pathways in each neuropathological condition

  20. Relationship of striatal 99Tcm-TRODAT-1 specific uptake and motor's severity in patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Bian Yanzhu; Liu Huang; Feng Jue; Wei Qiang; Li Jinfu; Liu Guozhang

    2004-01-01

    Objective: To investigate the relationship of striatal 99 Tc m -2β-((N, N'-bis (2-mercap-toethyl) ethylene diamino) methyl), 3β-(4-chlorophenyl) tropane, ( 99 Tc m -TRODAT-1) specific uptake values (SUVs) and motor's severity in patients with Parkinson's disease (PD). Methods: 35 patients with PD were examined by 99 Tc m -TRODAT-1 SPECT dopamine transporter brain imaging. The SUVs of the striatum and its subregions, including the putamen and caudate nucleus, were calculated by semi-quantity region of interest (ROI) technique with the radiation ratios of target/cerebellum. Motor's severity of PD was measured by Unified Parkinson's Disease Rating Scale (UPDRS). Motor UPDRS scores were divided into four subscales, bradykinesia scores, rigidity scores, postural instability scores and tremor scores. Results: SUVs of putamen correlated best with the motor UPDRS scores(r=-0.846, P<0.001), followed by that of striatum and caudate nucleus. Among the four major clinical signs of PD, the bradykinesia scores (X1) correlated best with SUVs of putamen(r=-0.858, P<0.001), followed by rigidity scores (X2) and postural instability scores. There was no significant correlation between tremor scores and SUVs of putamen (Y). A regression equation (Y=2.345-0.0418 X1-0.0580 X2) was founded by stepwise multiple linear regression analysis. Conclusions: The SUVs of striatum (especially SUVs of putamen) was a useful marker to evaluate the motor's severity of PD and monitor the progression of PD. (authors)

  1. Role of specific DNA mutations in the peripheral blood of colorectal cancer patients for the assessment of tumor stage and residual disease following tumor resection

    Science.gov (United States)

    Norcic, Gregor; Jelenc, Franc; Cerkovnik, Petra; Stegel, Vida; Novakovic, Srdjan

    2016-01-01

    In the present study, the detection of tumor-specific KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations in the peripheral blood of colorectal cancer (CRC) patients at all stages and adenomas was used for the estimation of disease stage prior to surgery and for residual disease following surgery. A total of 65 CRC patients were enrolled. The primary tumor tested positive for the specific mutations (KRAS mutations in codons 12, 13, 61, 117 or 146 and BRAF mutations in codon 600) in 35 patients. In all these patients, the specimen of normal bowel resected with the tumor was also tested for the presence of the same mutations in order to exclude the germ-line mutations. Only patients who tested positive for the specific mutation in the primary tumor were included in further analysis for the presence of tumor-specific mutation in the peripheral blood. No statistically significant differences were found between the detection rates of tumor mutations in the blood and different tumor stages (P=0.491). However, statistically significant differences in the proportions of patients with detected tumor-specific DNA mutations in the peripheral blood were found when comparing the groups of patients with R0 and R2 resections (P=0.038). Tumor-specific DNA mutations in the peripheral blood were more frequently detected in the patients with an incomplete surgical clearance of the tumor due to macroscopic residual disease (R2 resections). Therefore, the study concludes that the follow-up of somatic KRAS- and BRAF-mutated DNA in the peripheral blood of CRC patients may be useful in assessing the surgical clearance of the disease. PMID:27900004

  2. Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease

    Science.gov (United States)

    Mason, Kylie D.; Lin, Ann; Robb, Lorraine; Josefsson, Emma C.; Henley, Katya J.; Gray, Daniel H. D.; Kile, Benjamin T.; Roberts, Andrew W.; Strasser, Andreas; Huang, David C. S.; Waring, Paul; O’Reilly, Lorraine A.

    2013-01-01

    Dysregulation of the “intrinsic” apoptotic pathway is associated with the development of cancer and autoimmune disease. Bak and Bax are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic apoptotic pathway. Their activity is critical for the control of cell survival during lymphocyte development and homeostasis, best demonstrated by defects in thymic T-cell differentiation and peripheral lymphoid homeostasis caused by their combined loss. Because most bak−/−bax−/− mice die perinatally, the roles of Bax and Bak in immunological tolerance and prevention of autoimmune disease remain unclear. We show that mice reconstituted with a Bak/Bax doubly deficient hematopoietic compartment develop a fatal systemic lupus erythematosus-like autoimmune disease characterized by hypergammaglobulinemia, autoantibodies, lymphadenopathy, glomerulonephritis, and vasculitis. Importantly, these mice also develop a multiorgan autoimmune disease with autoantibodies against most solid glandular structures and evidence of glandular atrophy and necrotizing vasculitis. Interestingly, similar albeit less severe pathology was observed in mice containing a hematopoietic compartment deficient for only Bak, a phenotype reminiscent of the disease seen in patients with point mutations in BAK. These studies demonstrate a critical role for Bak and an ancillary role for Bax in safeguarding immunological tolerance and prevention of autoimmune disease. This suggests that direct activators of the intrinsic apoptotic pathway, such as BH3 mimetics, may be useful for treatment of diverse autoimmune diseases. PMID:23349374

  3. Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.

    Science.gov (United States)

    Scriba, Thomas J; Carpenter, Chelsea; Pro, Sebastian Carrasco; Sidney, John; Musvosvi, Munyaradzi; Rozot, Virginie; Seumois, Grégory; Rosales, Sandy L; Vijayanand, Pandurangan; Goletti, Delia; Makgotlho, Edward; Hanekom, Willem; Hatherill, Mark; Peters, Bjoern; Sette, Alessandro; Arlehamn, Cecilia S Lindestam

    2017-09-15

    Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.

  4. Homozygous deletion of six genes including corneodesmosin on chromosome 6p21.3 is associated with generalized peeling skin disease.

    Science.gov (United States)

    Teye, Kwesi; Hamada, Takahiro; Krol, Rafal P; Numata, Sanae; Ishii, Norito; Matsuda, Mitsuhiro; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

    2014-07-01

    Peeling skin syndrome (PSS) is a rare autosomal recessive form of ichthyosis showing skin exfoliation. PSS is divided into acral and generalized PSS, and the latter is further classified into non-inflammatory type (PSS type A) and inflammatory type (PSS type B). PSS type B is now called peeling skin disease (PSD). Different loss-of-function mutations in the corneodesmosin (CDSN) gene have been reported to cause PSD. The aim of this study was to determine genetic basis of disease in a 14-year-old Japanese patient with PSD. Immunohistochemical study showed lack of corneodesmosin (CDSN) in the skin, and standard PCR for genomic DNA failed to amplify CDSN product, suggesting CDSN defect. Multiplex ligation-dependent probe amplification and genomic quantitative real-time PCR analyses detected large homozygous deletion of 59,184bp extending from 40.6kb upstream to 13.2kb downstream of CDSN, which included 6 genes (TCF19, CCHCR1, PSORS1C2, PSORS1C1, CDSN and C6orf15). The continuous gene lost did not result in additional clinical features. Inverted repeats with 85% similarity flanking the deletion breakpoint were considered to mediate the deletion by non-homologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication. Parents were clinically unaffected and were heterozygote carriers of the same deletion, which was absent in 284 ethnically matched control alleles. We also developed simple PCR method, which is useful for detection of this deletion. Although 5 other genes were also deleted, homozygous deletion of CDSN was considered to be responsible for this PSD. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Disease-specific health-related quality of life instruments for IgE-mediated food allergy

    DEFF Research Database (Denmark)

    Salvilla, S A; Dubois, A E J; Flokstra-de Blok, B M J

    2014-01-01

    of the impact of, and investigations and interventions for, IgE-mediated food allergy on health-related quality of life (HRQL). Using a sensitive search strategy, we searched seven electronic bibliographic databases to identify disease-specific quality of life (QOL) tools relating to IgE-mediated food allergy...

  6. High frequency of cytolytic 21-Hydroxylase specific CD8+ T cells in autoimmune Addison’s disease patients1

    Science.gov (United States)

    Dawoodji, Amina; Chen, Ji-Li; Shepherd, Dawn; Dalin, Frida; Tarlton, Andrea; Alimohammadi, Mohammad; Penna-Martinez, Marissa; Meyer, Gesine; Mitchell, Anna L; Gan, Earn H; Bratland, Eirik; Bensing, Sophie; Husebye, Eystein; Pearce, Simon H.; Badenhoop, Klaus; Kämpe, Olle; Cerundolo, Vincenzo

    2016-01-01

    The mechanisms behind the destruction of the adrenal glands in autoimmune Addison’s disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in over 90% of patients, but these autoantibodies are not thought to mediate the disease. Here we demonstrate highly frequent 21-hydroxylase specific T cells detectable in 20 patients with Addison’s disease. Using overlapping 18aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8+ and CD4+ T cell responses in a large proportion of Addison’s patients both ex-vivo and after in-vitro culture of peripheral blood lymphocytes up to 20 years after diagnosis. In a large proportion of patients, CD8+ 21-hydroxylase specific T cells and CD4+ 21-hydroxylase specific T cells were very abundant and detectable in ex-vivo assays. HLA class-I tetramer-guided isolation of 21-hydroxylase specific CD8+ T cells showed their ability to lyse 21-hydroxylase positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate strong cytotoxic T lymphocyte responses to 21-hydroxylase often occur in-vivo, and that reactive cytotoxic T lymphocytes have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. PMID:25063864

  7. Disease-specific health-related quality of life instruments for IgE-mediated food allergy.

    Science.gov (United States)

    Salvilla, S A; Dubois, A E J; Flokstra-de Blok, B M J; Panesar, S S; Worth, A; Patel, S; Muraro, A; Halken, S; Hoffmann-Sommergruber, K; DunnGalvin, A; Hourihane, J O'B; Regent, L; de Jong, N W; Roberts, G; Sheikh, A

    2014-07-01

    This is one of seven interlinked systematic reviews undertaken on behalf of the European Academy of Allergy and Clinical Immunology as part of their Guidelines for Food Allergy and Anaphylaxis, which focuses on instruments developed for IgE-mediated food allergy. Disease-specific questionnaires are significantly more sensitive than generic ones in measuring the response to interventions or future treatments, as well as estimating the general burden of food allergy. The aim of this systematic review was therefore to identify which disease-specific, validated instruments can be employed to enable assessment of the impact of, and investigations and interventions for, IgE-mediated food allergy on health-related quality of life (HRQL). Using a sensitive search strategy, we searched seven electronic bibliographic databases to identify disease-specific quality of life (QOL) tools relating to IgE-mediated food allergy. From the 17 eligible studies, we identified seven disease-specific HRQL instruments, which were then subjected to detailed quality appraisal. This revealed that these instruments have undergone formal development and validation processes, and have robust psychometric properties, and therefore provide a robust means of establishing the impact of food allergy on QOL. Suitable instruments are now available for use in children, adolescents, parents/caregivers, and adults. Further work must continue to develop a clinical minimal important difference for food allergy and for making these instruments available in a wider range of European languages. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Survival after Liver Transplantation in the United States: A Disease-Specific Analysis of the UNOS database

    Czech Academy of Sciences Publication Activity Database

    Roberts, M.S.; Angus, D.C.; Bryce, C.L.; Valenta, Zdeněk; Weissfeld, L.

    2004-01-01

    Roč. 10, č. 7 (2004), s. 886-897 ISSN 1527-6465 Source of funding: V - iné verejné zdroje Keywords : disease-specific survival * liver transplantation * cox PH model Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 3.984, year: 2004

  9. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta-analysis.

    Science.gov (United States)

    Moraros, John; Nwankwo, Chijioke; Patten, Scott B; Mousseau, Darrell D

    2017-03-01

    To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention. © 2016 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

  10. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta‐analysis

    Science.gov (United States)

    Moraros, John; Nwankwo, Chijioke; Patten, Scott B.

    2016-01-01

    1 Objective To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). 2 Method We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. 3 Results Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). 4 Conclusions Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention. PMID:28029715

  11. [Specific features of mammographic visualization of "small" breast tumors developing on the background of fibrocystic disease].

    Science.gov (United States)

    Bukharin, D G; Velichko, S A; Slonimskaia, E M; Frolova, I G; Luneva, S V; Garbukov, E Iu; Doroshenko, A V

    2011-01-01

    All complications diagnosed at early stages of breast cancer were associated with small tumors, especially with those arising in the aftermath of fibrocystic disease. Hence, our task was to study the XR-semiotics of lesions of less than 15 mm in diameter and of the same origin. 100 mammograms of breast cancer patients with benign disease of the breast were studied. The presence of moderate-to-severe fibrocystic disease significantly affected the visualization of lesions of less than 10 mm in diameter. Since the XR-semiotics of small tumors failed to reveal malignancy features, all lesions visualized by mammography required additional diagnostic procedures using ultrasound and invasive radiology.

  12. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks

    Science.gov (United States)

    Glicksberg, Benjamin S.; Li, Li; Badgeley, Marcus A.; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D.; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L.; Hoffman, Gabriel E.; Dan Li, Shuyu; Schadt, Eric E.; Patel, Chirag J.; Chen, Rong; Dudley, Joel T.

    2016-01-01

    Motivation: Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). Results: We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key ‘hub’ diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. Contacts: rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307606

  13. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks.

    Science.gov (United States)

    Glicksberg, Benjamin S; Li, Li; Badgeley, Marcus A; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L; Hoffman, Gabriel E; Dan Li, Shuyu; Schadt, Eric E; Patel, Chirag J; Chen, Rong; Dudley, Joel T

    2016-06-15

    Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key 'hub' diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  14. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  15. The promise of discovering population-specific disease-associated genes in South Asia.

    Science.gov (United States)

    Nakatsuka, Nathan; Moorjani, Priya; Rai, Niraj; Sarkar, Biswanath; Tandon, Arti; Patterson, Nick; Bhavani, Gandham SriLakshmi; Girisha, Katta Mohan; Mustak, Mohammed S; Srinivasan, Sudha; Kaushik, Amit; Vahab, Saadi Abdul; Jagadeesh, Sujatha M; Satyamoorthy, Kapaettu; Singh, Lalji; Reich, David; Thangaraj, Kumarasamy

    2017-09-01

    The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups. We identified 81 unique groups, 14 of which had estimated census sizes of more than 1 million, that descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. We identified multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an underappreciated opportunity for decreasing disease burden among South Asians through discovery of and testing for recessive disease-associated genes.

  16. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

    DEFF Research Database (Denmark)

    Gusev, Alexander; Lee, S Hong; Trynka, Gosia

    2014-01-01

    Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common...... diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach...... partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment...

  17. Atrophy-specific MRI brain template for Alzheimer's disease and mild cognitive impairment

    DEFF Research Database (Denmark)

    Fonov, Vladimir; Coupe, Pierrick; Eskildsen, Simon Fristed

    Background Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) [1]. Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD....... Alzheimer's and Dementia, 2010. 6(4, Supplement 1). [3] Fonov, V, et al. NeuroImage, 2011. 54(1).......Background Rapid brain loss is characteristic for the patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) [1]. Increase of the lateral ventricular volume is strongly correlated with the progression of the disease. High variability in the degree of atrophy for subjects with AD...... of the brain and the contrast between different tissue types for the given level of atrophy. Figure 1 shows images through 6 example values of increasing RLVV. Conclusions The proposed method and resulting template will be useful tools for the development of robust automatic image processing methods targeted...

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

    Science.gov (United States)

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

    2003-12-01

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

  19. Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients.

    Directory of Open Access Journals (Sweden)

    Arndt Rolfs

    Full Text Available Gaucher disease (GD is the most common lysosomal storage disorder (LSD. Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs.Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD.

  20. Application of a disease-specific mapping function to estimate utility gains with effective treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Rupnow Marcia FT

    2005-09-01

    Full Text Available Abstract Background Most tools for estimating utilities use clinical trial data from general health status models, such as the 36-Item Short-Form Health Survey (SF-36. A disease-specific model may be more appropriate. The objective of this study was to apply a disease-specific utility mapping function for schizophrenia to data from a large, 1-year, open-label study of long-acting risperidone and to compare its performance with an SF-36-based utility mapping function. Methods Patients with schizophrenia or schizoaffective disorder by DSM-IV criteria received 25, 50, or 75 mg long-acting risperidone every 2 weeks for 12 months. The Positive and Negative Syndrome Scale (PANSS and SF-36 were used to assess efficacy and health-related quality of life. Movement disorder severity was measured using the Extrapyramidal Symptom Rating Scale (ESRS; data concerning other common adverse effects (orthostatic hypotension, weight gain were collected. Transforms were applied to estimate utilities. Results A total of 474 patients completed the study. Long-acting risperidone treatment was associated with a utility gain of 0.051 using the disease-specific function. The estimated gain using an SF-36-based mapping function was smaller: 0.0285. Estimates of gains were only weakly correlated (r = 0.2. Because of differences in scaling and variance, the requisite sample size for a randomized trial to confirm observed effects is much smaller for the disease-specific mapping function (156 versus 672 total subjects. Conclusion Application of a disease-specific mapping function was feasible. Differences in scaling and precision suggest the clinically based mapping function has greater power than the SF-36-based measure to detect differences in utility.

  1. Psychometric properties of HeartQoL, a core heart disease-specific health-related quality of life questionnaire, in Danish implantable cardioverter defibrillator recipients

    DEFF Research Database (Denmark)

    Zangger, Graziella; Zwisler, Ann-Dorthe; Kikkenborg Berg, Selina

    2018-01-01

    disease-specific health-related quality of life questionnaire, in implantable cardioverter defibrillator recipients. Design This study involved cross-sectional and test-retest study designs. Method Implantable cardioverter defibrillator recipients in the cross-sectional study completed the Heart......QoL, the Short-Form 36 Health Survey, and the Hospital Anxiety and Depression Scale. The HeartQoL structure, construct-related validity (convergent and discriminative) and reliability (internal consistency) were assessed. HeartQoL reproducibility (test-retest) was assessed in an independent sample of implantable...... psychometric attributes of validity and reliability in this implantable cardioverter defibrillator population. This study adds support for the HeartQoL as a core heart-specific health-related quality of life questionnaire in a broad group of patients with heart disease including implantable cardioverter...

  2. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    Science.gov (United States)

    Lewis, Wesley R; Malarkey, Erik B; Tritschler, Douglas; Bower, Raqual; Pasek, Raymond C; Porath, Jonathan D; Birket, Susan E; Saunier, Sophie; Antignac, Corinne; Knowles, Michael R; Leigh, Margaret W; Zariwala, Maimoona A; Challa, Anil K; Kesterson, Robert A; Rowe, Steven M; Drummond, Iain A; Parant, John M; Hildebrandt, Friedhelm; Porter, Mary E; Yoder, Bradley K; Berbari, Nicolas F

    2016-07-01

    Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in

  3. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    Directory of Open Access Journals (Sweden)

    Wesley R Lewis

    2016-07-01

    Full Text Available Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400. While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8. GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC protein 4 (DRC4 where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR to generate one of these human missense

  4. Extracellular and Intracellular Cyclophilin A, Native and Post-Translationally Modified, Show Diverse and Specific Pathological Roles in Diseases.

    Science.gov (United States)

    Xue, Chao; Sowden, Mark P; Berk, Bradford C

    2018-05-01

    CypA (cyclophilin A) is a ubiquitous and highly conserved protein with peptidyl prolyl isomerase activity. Because of its highly abundant level in the cytoplasm, most studies have focused on the roles of CypA as an intracellular protein. However, emerging evidence suggests an important role for extracellular CypA in the pathogenesis of several diseases through receptor (CD147 or other)-mediated autocrine and paracrine signaling pathways. In this review, we will discuss the shared and unique pathological roles of extracellular and intracellular CypA in human cardiovascular diseases. In addition, the evolving role of post-translational modifications of CypA in the pathogenesis of disease is discussed. Finally, recent studies with drugs specific for extracellular CypA show its importance in disease pathogenesis in several animal models and make extracellular CypA a new therapeutic target. © 2018 American Heart Association, Inc.

  5. Polycystic ovarian disease: endocrinological parameters with specific reference to growth hormone and somatomedin-C.

    Science.gov (United States)

    Urdl, W

    1988-01-01

    Thirty-three women (22-38 years old) with polycystic ovarian disease (PCOD) were included in this study. The criteria for diagnosis were: an LH/FSH ratio greater than 2.0; polycystic ovaries, diagnosed by means of palpation and ultrasound; androgenism and menstrual cycle abnormalities. Using endocrine parameters, we attempted to define distinct forms of PCOD. The patients were placed in three groups according to serum levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17 alpha OHP) and the estrone/androstendione (E1/delta 4A) ratio. Patients in group I (n = 18) had an elevated T level (greater than 1.0 ng/ml) and a 17 alpha OHP level under 4.0 ng/ml. This type of POCD was called the "androgen" type. Patients in group II (n = 7) had normal T- and 17 alpha OHP levels under 4.0 ng/ml and an elevated (E1/delta 4A) ratio. This type of PCOD was called the "estrogen" type. Group III (n = 8) comprised patients with 17 alpha OHP levels over 4.0 ng/ml. This type of PCOD was called the "adrenocortical" type. In two patients of this group, a modified ACTH test revealed late-onset congenital hyperplasia. The endocrine parameters of the patients with PCOD were compared with those of 17 adult without signs of PCOD. Statistical evaluation was done by variance analysis. Women with acromegaly often show signs of androgenism as well as menstrual cycle abnormalities. This may indicate an association between the growth factors human growth hormone (HGH) and somatomedin-C (Sm-C) and the biosynthese and metabolism of steroid hormone. Recent experiments have demonstrated such associations. Our study showed an association between the HGH and Sm-C levels and abnormal steroid hormone concentrations in women with androgen type PCOD (group I). These patients had a significantly decreased HGH level, a significantly decreased HGH/Sm-C ratio, and an increased average Sm-C level. These data suggest that elevated Sm-C levels can, by a negative-feedback mechanism, inhibit pituitary HGH

  6. Determinants of Gastroesophageal Reflux Disease, Including Hookah Smoking and Opium Use– A Cross-Sectional Analysis of 50,000 Individuals

    Science.gov (United States)

    Islami, Farhad; Nasseri-Moghaddam, Siavosh; Pourshams, Akram; Poustchi, Hossein; Semnani, Shahryar; Kamangar, Farin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M.; Pharoah, Paul D.; Brennan, Paul; Abnet, Christian C.; Boffetta, Paolo; Malekzadeh, Reza

    2014-01-01

    Background Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. Methods We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. Results Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02–1.75) and opium use (OR 1.70, 95% CI 1.55–1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76–0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). Conclusion GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere. PMID:24586635

  7. Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- a cross-sectional analysis of 50,000 individuals.

    Science.gov (United States)

    Islami, Farhad; Nasseri-Moghaddam, Siavosh; Pourshams, Akram; Poustchi, Hossein; Semnani, Shahryar; Kamangar, Farin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M; Pharoah, Paul D; Brennan, Paul; Abnet, Christian C; Boffetta, Paolo; Malekzadeh, Reza

    2014-01-01

    Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼ 50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75) and opium use (OR 1.70, 95% CI 1.55-1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.

  8. Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- a cross-sectional analysis of 50,000 individuals.

    Directory of Open Access Journals (Sweden)

    Farhad Islami

    Full Text Available Gastroesophageal reflux disease (GERD is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time.We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼ 50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn.Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75 and opium use (OR 1.70, 95% CI 1.55-1.87 were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99. After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined.GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.

  9. Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.

    Science.gov (United States)

    Fan, Bo; Hu, Bin; Yuan, Qingmin; Wen, Shuang; Liu, Tianqing; Bai, Shanshan; Qi, Xiaofeng; Wang, Xin; Yang, Deyong; Sun, Xiuzhen; Song, Xishuang

    2017-07-01

    Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC

  10. Validation of inverse seasonal peak mortality in medieval plagues, including the Black Death, in comparison to modern Yersinia pestis-variant diseases.

    Science.gov (United States)

    Welford, Mark R; Bossak, Brian H

    2009-12-22

    Recent studies have noted myriad qualitative and quantitative inconsistencies between the medieval Black Death (and subsequent "plagues") and modern empirical Y. pestis plague data, most of which is derived from the Indian and Chinese plague outbreaks of A.D. 1900+/-15 years. Previous works have noted apparent differences in seasonal mortality peaks during Black Death outbreaks versus peaks of bubonic and pneumonic plagues attributed to Y. pestis infection, but have not provided spatiotemporal statistical support. Our objective here was to validate individual observations of this seasonal discrepancy in peak mortality between historical epidemics and modern empirical data. We compiled and aggregated multiple daily, weekly and monthly datasets of both Y. pestis plague epidemics and suspected Black Death epidemics to compare seasonal differences in mortality peaks at a monthly resolution. Statistical and time series analyses of the epidemic data indicate that a seasonal inversion in peak mortality does exist between known Y. pestis plague and suspected Black Death epidemics. We provide possible explanations for this seasonal inversion. These results add further evidence of inconsistency between historical plagues, including the Black Death, and our current understanding of Y. pestis-variant disease. We expect that the line of inquiry into the disputed cause of the greatest recorded epidemic will continue to intensify. Given the rapid pace of environmental change in the modern world, it is crucial that we understand past lethal outbreaks as fully as possible in order to prepare for future deadly pandemics.

  11. Validation of inverse seasonal peak mortality in medieval plagues, including the Black Death, in comparison to modern Yersinia pestis-variant diseases.

    Directory of Open Access Journals (Sweden)

    Mark R Welford

    Full Text Available BACKGROUND: Recent studies have noted myriad qualitative and quantitative inconsistencies between the medieval Black Death (and subsequent "plagues" and modern empirical Y. pestis plague data, most of which is derived from the Indian and Chinese plague outbreaks of A.D. 1900+/-15 years. Previous works have noted apparent differences in seasonal mortality peaks during Black Death outbreaks versus peaks of bubonic and pneumonic plagues attributed to Y. pestis infection, but have not provided spatiotemporal statistical support. Our objective here was to validate individual observations of this seasonal discrepancy in peak mortality between historical epidemics and modern empirical data. METHODOLOGY/PRINCIPAL FINDINGS: We compiled and aggregated multiple daily, weekly and monthly datasets of both Y. pestis plague epidemics and suspected Black Death epidemics to compare seasonal differences in mortality peaks at a monthly resolution. Statistical and time series analyses of the epidemic data indicate that a seasonal inversion in peak mortality does exist between known Y. pestis plague and suspected Black Death epidemics. We provide possible explanations for this seasonal inversion. CONCLUSIONS/SIGNIFICANCE: These results add further evidence of inconsistency between historical plagues, including the Black Death, and our current understanding of Y. pestis-variant disease. We expect that the line of inquiry into the disputed cause of the greatest recorded epidemic will continue to intensify. Given the rapid pace of environmental change in the modern world, it is crucial that we understand past lethal outbreaks as fully as possible in order to prepare for future deadly pandemics.

  12. Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease.

    Science.gov (United States)

    Middeldorp, Jaap M

    2015-01-01

    Epstein-Barr virus (EBV) is widely distributed in the world and associated with a still increasing number of acute, chronic, malignant and autoimmune disease syndromes. Humoral immune responses to EBV have been studied for diagnostic, pathogenic and protective (vaccine) purposes. These studies use a range of methodologies, from cell-based immunofluorescence testing to antibody-diversity analysis using immunoblot and epitope analysis using recombinant or synthetic peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D), EA(R) and EBNA) are defined at cellular and molecular levels, providing a historic overview. The characteristic antibody responses to these complexes in health and disease are described, and differences are highlighted by clinical examples. Options for EBV vaccination are briefly addressed. For a selected number of immunodominant proteins, in particular EBNA1, the interaction with human antibodies is further detailed at the epitope level, revealing interesting insights for structure, function and immunological aspects, not considered previously. Humoral immune responses against EBV-encoded tumour antigens LMP1, LMP2 and BARF1 are addressed, which provide novel options for targeted immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are given, and mechanisms of antigen mimicry are briefly discussed. Further analysis of humoral immune responses against EBV in health and disease in carefully selected patient cohorts will open new options for understanding pathogenesis of individual EBV-linked diseases and developing targeted diagnostic and therapeutic approaches.

  13. Differentiation of five strains of infectious bursal disease virus: Development of a strain-specific multiplex PCR

    DEFF Research Database (Denmark)

    Kusk, M.; Kabell, Susanne; Jørgensen, Poul Henrik

    2005-01-01

    and histopathology. Since these methods are laborious and have low specificity alternatives are needed. In the present study, we report the development of a strain-specific multiplex RT-PCR technique, which can detect and differentiate between field strains of IBDV and vaccine virus strains including a so-called hot...

  14. High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients.

    Science.gov (United States)

    Dawoodji, Amina; Chen, Ji-Li; Shepherd, Dawn; Dalin, Frida; Tarlton, Andrea; Alimohammadi, Mohammad; Penna-Martinez, Marissa; Meyer, Gesine; Mitchell, Anna L; Gan, Earn H; Bratland, Eirik; Bensing, Sophie; Husebye, Eystein S; Pearce, Simon H; Badenhoop, Klaus; Kämpe, Olle; Cerundolo, Vincenzo

    2014-09-01

    The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

  15. High-frequency oscillatory ventilation in pediatric acute hypoxemic respiratory failure: disease-specific morbidity survival analysis.

    Science.gov (United States)

    Babbitt, Christopher J; Cooper, Michael C; Nussbaum, Eliezer; Liao, Eileen; Levine, Glenn K; Randhawa, Inderpal S

    2012-12-01

    Multiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity. A retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality. A total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05). High-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV.

  16. Specific perfusion pattern in stress 201Tl myocardial scintigraphy of left main coronary artery disease

    International Nuclear Information System (INIS)

    Wakasugi, Shigetoshi; Shibata, Nobuhiko; Kobayashi, Tohru; Fudemoto, Yoshiyuki; Hasegawa, Yoshihisa; Nakano, Shunichi

    1986-01-01

    The usefulness of stress 201 Tl myocardial scintigraphy for identifying left main coronary artery disease was evaluated with data from 23 patients with 50% or more narrowing of the left main coronary artery and 56 patients with 75% or more narrowing of the major coronary arteries but without left main coronary artery involvement (no left main coronary artery disease). Quantitative evaluation of stress perfusion scintigrams in all five patients with narrowing of the left main coronary artery of 90% or more showed a characteristic perfusion pattern (left main pattern) of extensive homogeneous defect over the whole anterolateral segment and simultaneous defects in all radii of the high anteroseptal and high posterolateral segments. On the other hand, such a perfusion pattern was noted in only 1 of 18 patients with less than 90% stenosis of the left main coronary artery and in only 1 of 56 patients with no left coronary artery disease. (orig.)

  17. Time series modeling of pathogen-specific disease probabilities with subsampled data.

    Science.gov (United States)

    Fisher, Leigh; Wakefield, Jon; Bauer, Cici; Self, Steve

    2017-03-01

    Many diseases arise due to exposure to one of multiple possible pathogens. We consider the situation in which disease counts are available over time from a study region, along with a measure of clinical disease severity, for example, mild or severe. In addition, we suppose a subset of the cases are lab tested in order to determine the pathogen responsible for disease. In such a context, we focus interest on modeling the probabilities of disease incidence given pathogen type. The time course of these probabilities is of great interest as is the association with time-varying covariates such as meteorological variables. In this set up, a natural Bayesian approach would be based on imputation of the unsampled pathogen information using Markov Chain Monte Carlo but this is computationally challenging. We describe a practical approach to inference that is easy to implement. We use an empirical Bayes procedure in a first step to estimate summary statistics. We then treat these summary statistics as the observed data and develop a Bayesian generalized additive model. We analyze data on hand, foot, and mouth disease (HFMD) in China in which there are two pathogens of primary interest, enterovirus 71 (EV71) and Coxackie A16 (CA16). We find that both EV71 and CA16 are associated with temperature, relative humidity, and wind speed, with reasonably similar functional forms for both pathogens. The important issue of confounding by time is modeled using a penalized B-spline model with a random effects representation. The level of smoothing is addressed by a careful choice of the prior on the tuning variance. © 2016, The International Biometric Society.

  18. Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease

    Science.gov (United States)

    Geelhaar, Anika; Moos, Verena; Schinnerling, Katina; Allers, Kristina; Loddenkemper, Christoph; Fenollar, Florence; LaScola, Bernard; Raoult, Didier; Schneider, Thomas

    2010-01-01

    Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response toward T. whipplei. This T. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolish T. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection. PMID:20696822

  19. Measuring disease-specific quality of life in rare populations: a practical approach to cross-cultural translation

    Directory of Open Access Journals (Sweden)

    Riedlinger Arne

    2009-10-01

    Full Text Available Abstract Background Disease-specific quality of life (QoL measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder. Procedure A measurement study was conducted in the United Kingdom (UK, France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries. Results This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT, were performed in children with immune thrombocytopenic purpura (ITP. The KIT was translated from North American English into UK English, French, German, and Spanish. Conclusion This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.

  20. Sector-wide or disease-specific? Implications of trends in development assistance for health for the SDG era.

    Science.gov (United States)

    Buffardi, Anne L

    2018-04-01

    The record of the Millennium Development Goals broadly reflects the trade-offs of disease-specific financing: substantial progress in particular areas, facilitated by time-bound targets that are easy to measure and communicate, which shifted attention and resources away from other areas, masked inequalities and exacerbated fragmentation. In many ways, the Sustainable Development Goals reflect a profound shift towards a more holistic, system-wide approach. To inform responses to this shift, this article builds upon existing work on aggregate trends in donor financing, bringing together what have largely been disparate analyses of sector-wide and disease-specific financing approaches. Looking across the last 26 years, the article examines how international donors have allocated development assistance for health (DAH) between these two approaches and how attempts to bridge them have fared in practice. Since 1990, DAH has overwhelmingly favoured disease-specific earmarks over health sector support, with the latter peaking in 1998. Attempts to integrate system strengthening elements into disease-specific funding mechanisms have varied by disease, and more integrated funding platforms have failed to gain traction. Health sector support largely remains an unfulfilled promise: proportionately low amounts (albeit absolute increases) which have been inconsistently allocated, and the overall approach inconsistently applied in practice. Thus, the expansive orientation of the Sustainable Development Goals runs counter to trends over the last several decades. Financing proposals and efforts to adapt global health institutions must acknowledge and account for the persistent challenges in the financing and implementation of integrated, cross-sector policies. National and subnational experimentation may offer alternatives within and beyond the health sector.

  1. A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

    Directory of Open Access Journals (Sweden)

    Warren D Anderson

    2017-07-01

    Full Text Available Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension. We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

  2. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites.

    Directory of Open Access Journals (Sweden)

    Daniel R Feikin

    Full Text Available BACKGROUND: Vaccine-serotype (VT invasive pneumococcal disease (IPD rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7 into national immunization programs. Increases in non-vaccine-serotype (NVT IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65 and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68. Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10, while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71. Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]. CONCLUSIONS: Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not

  3. Association of some specific nutrient deficiencies with periodontal disease in elderly people: A systematic literature review.

    NARCIS (Netherlands)

    Putten, G.J. van der; Vanobbergen, J.N.; Visschere, L. De; Schols, J.G.J.H.; Baat, C. de

    2009-01-01

    OBJECTIVE: Deficiency of vitamin B complex, vitamin C, vitamin D, calcium, and magnesium has been associated with periodontal disease. This article systematically reviews the currently available literature on the feasible association of vitamin B complex, vitamin C, vitamin D, calcium, and magnesium

  4. Profile of Generic and Disease-Specific Health-Related Quality of ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    However the social support dimension was not impaired. ... We studied 36 patients with clinical diagnosis of PD who were ... moderate problem: and 3= extreme problem)21 ... population were tested using the Students t- test. .... adjustment of items in the social support subscale ... Global Parkinson's Disease Survey (GPDS).

  5. Chronic pruritus in the absence of specific skin disease: an update on pathophysiology, diagnosis, and therapy.

    Science.gov (United States)

    Cassano, Nicoletta; Tessari, Gianpaolo; Vena, Gino A; Girolomoni, Giampiero

    2010-12-01

    Chronic pruritus is a major and distressing symptom of many cutaneous and systemic diseases and can significantly impair the patient's quality of life. Pruritus perception is the final result of a complex network involving dedicated nerve pathways and brain areas, and an increasing number of peripheral and central mediators are thought to be involved. Itch is associated with most cutaneous disorders and, in these circumstances, its management overlaps with that of the skin disease. Itch can also occur without associated skin diseases or primary skin lesions, but only with nonspecific lesions secondary to rubbing or scratching. Chronic itch with no or minimal skin changes can be secondary to important diseases, such as neurologic disorders, chronic renal failure, cholestasis, systemic infections, malignancies, and endocrine disorders, and may also result from exposure to some drugs. The search for the cause of pruritus usually requires a meticulous step-by-step assessment involving careful history taking as well as clinical examination and laboratory investigations. Few evidence-based treatments for pruritus are available. Topical therapy, oral histamine H(1) receptor antagonists, and phototherapy with UV radiation can target pruritus elicitation in the skin, whereas antiepileptic drugs, opioid receptor antagonists, and antidepressants can block signal processing in the CNS.

  6. The Age-Specific Quantitative Effects of Metabolic Risk Factors on Cardiovascular Diseases and Diabetes

    DEFF Research Database (Denmark)

    Singh, Gitanjali M; Danaei, Goodarz; Farzadfar, Farshad

    2013-01-01

    The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex...

  7. Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response

    Science.gov (United States)

    Background: Celiac disease is an immune-mediated enteropathy that is generally understood to be triggered by the ingestion of gluten proteins of wheat and related cereals. The skin manifestation of the condition is known as dermatitis herpetiformis. Antibody response to native and deamidated seque...

  8. The ethnicity-specific association of biomarkers with the angiographic severity of coronary artery disease

    NARCIS (Netherlands)

    Gijsberts, C M; Bank, I E M; Seneviratna, A; den Ruijter, H M; Asselbergs, F W; Agostoni, P; Remijn, J A; Pasterkamp, G; Kiat, H C; Roest, M; Richards, A M; Chan, M Y; de Kleijn, D P V; Hoefer, I E

    BACKGROUND: Risk factor burden and clinical characteristics of patients with coronary artery disease (CAD) differ among ethnic groups. We related biomarkers to CAD severity in Caucasians, Chinese, Indians and Malays. METHODS: In the Dutch-Singaporean UNICORN coronary angiography cohort (n = 2033) we

  9. Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis

    DEFF Research Database (Denmark)

    Wuttge, D. M.; Carlsen, A. L.; Teku, G.

    2015-01-01

    Objective. To evaluate the expression profiles of cell-free plasma miRNAs in SSc and to characterize their correlation with disease subgroups (lcSSc and dcSSc) and with autoantibody profiles. Methods. Using quantitative RT-PCR, the abundance of 45 mature miRNAs in plasma was determined in 95 pati...

  10. Nocturia: A non-specific but important symptom of urological disease

    NARCIS (Netherlands)

    Schneider, Tim; de la Rosette, Jean Jmch; Michel, Martin C.

    2009-01-01

    Nocturia is a prevalent symptom that can adversely affect quality of sleep and overall quality of life leading to morbidity and even mortality. Nocturia can be due to a range of urological conditions and non-urological diseases. Nocturia can be due to an insufficient bladder capacity and/or

  11. Characteristics of specific immunological indicators in patients with postoperative relapse of Graves’ disease

    Directory of Open Access Journals (Sweden)

    Yu.V. Buldigina

    2018-02-01

    Full Text Available Background. Activity of autoimmune processes had a leading role in the development of relapse of hyperthyroidism. Level of thyroid-stimulating hormone (TSH receptor antibodies is a basic factor that predetermines the relapse and can be used as a criterion to evaluate its development. A research aim was to study the structural and functional state of the thyroid gland, levels of thyroid peroxidase antibodies and TSH receptor antibodies in patients with postoperative relapse of Graves’ disease during antithyroid therapy. Mate­rials and methods. The group of patients consisted of 25 wo­men aged 23 to 73 years (an average of 53.56 ± 2.31 years. The period from the first surgical treatment to the development of relapse of thyrotoxicosis ranged from 1 to 29 years and avera­ged 13.33 ± 1.66 years. Results. It was found that the le­vels of TSH receptor antibodies, which are the main factors in the pathogenesis of Graves’ disease, are not decreased on the background of drug treatment that indicates a lack of perspective of conservative therapy for the post-operative relapse of this disease. Conclusions. When the state of medication compensation for thyrotoxicosis is achieved, it is recommended to conduct the therapy with I131 or surgical treatment of the relapse of Graves’ disease.

  12. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

    DEFF Research Database (Denmark)

    Howson, Joanna M. M.; Zhao, Wei; Barnes, Daniel R

    2017-01-01

    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy ...

  13. Report of two patients with Paget′s disease - one with typical clinical and radiological manifestations including cardiac involvement and the other subclinical but with radiological changes

    Directory of Open Access Journals (Sweden)

    B Sivapatha Sundharam

    2006-01-01

    Full Text Available Osteitis deformans or Paget′s disease of bone, fondly referred to as the ′collage of matrix madness′, is a unique skeletal disease characterized by furious osteoclastic bone resorption followed by a period of hectic bone formation, resulting in again in the bone mass wherein the newly formed bone is disordered and architecturally unsound. A disease of obscure etiology, it usually manifests as progressive enlargement of one or multiple bones of the skeleton. Herewith we present a typical example of a polyostotic form of Paget′s disease with classical clinical features and radiologic changes in one patient and a subclinical form of Paget′s disease with marked radiological changes in the other patient.

  14. HY-Specific Induced Regulatory T Cells Display High Specificity and Efficacy in the Prevention of Acute Graft-versus-Host Disease.

    Science.gov (United States)

    Li, Jun; Heinrichs, Jessica; Haarberg, Kelley; Semple, Kenrick; Veerapathran, Anandharaman; Liu, Chen; Anasetti, Claudio; Yu, Xue-Zhong

    2015-07-15

    Naturally derived regulatory T cells (Tregs) may prevent graft-versus-host disease (GVHD) while preserving graft-versus-leukemia (GVL) activity. However, clinical application of naturally derived regulatory T cells has been severely hampered by their scarce availability and nonselectivity. To overcome these limitations, we took alternative approaches to generate Ag-specific induced Tregs (iTregs) and tested their efficacy and selectivity in the prevention of GVHD in preclinical models of bone marrow transplantation. We selected HY as a target Ag because it is a naturally processed, ubiquitously expressed minor histocompatibility Ag (miHAg) with a proven role in GVHD and GVL effect. We generated HY-specific iTregs (HY-iTregs) from resting CD4 T cells derived from TCR transgenic mice, in which CD4 cells specifically recognize HY peptide. We found that HY-iTregs were highly effective in preventing GVHD in male (HY(+)) but not female (HY(-)) recipients using MHC II-mismatched, parent→F1, and miHAg-mismatched murine bone marrow transplantation models. Interestingly, the expression of target Ag (HY) on the hematopoietic or nonhematopoietic compartment alone was sufficient for iTregs to prevent GVHD. Furthermore, treatment with HY-iTregs still preserved the GVL effect even against pre-established leukemia. We found that HY-iTregs were more stable in male than in female recipients. Furthermore, HY-iTregs expanded extensively in male but not female recipients, which in turn significantly reduced donor effector T cell expansion, activation, and migration into GVHD target organs, resulting in effective prevention of GVHD. This study demonstrates that iTregs specific for HY miHAgs are highly effective in controlling GVHD in an Ag-dependent manner while sparing the GVL effect. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Applications of Patient-Specific Induced Pluripotent Stem Cells; Focused on Disease Modeling, Drug Screening and Therapeutic Potentials for Liver Disease

    OpenAIRE

    Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

    2010-01-01

    The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of...

  16. Sex-specific effect of juvenile diet on adult disease resistance in a field cricket.

    Directory of Open Access Journals (Sweden)

    Clint D Kelly

    Full Text Available Food limitation is expected to reduce an individual's body condition (body mass scaled to body size and cause a trade-off between growth and other fitness-related traits, such as immunity. We tested the condition-dependence of growth and disease resistance in male and female Gryllus texensis field crickets by manipulating diet quality via nutrient content for their entire life and then subjecting individuals to a host resistance test using the live bacterium Serratia marcescens. As predicted, crickets on a high-quality diet eclosed more quickly, and at a larger body size and mass. Crickets on a high-quality diet were not in better condition at the time of eclosion, but they were in better condition 7-11 days after eclosion, with females also being in better condition than males. Despite being in better condition, however, females provided with a high-quality diet had significantly poorer disease resistance than females on a low-quality diet and in poor condition. Similarly, males on low- and high-quality diets did not differ in their disease resistance, despite differing in their body condition. A sex difference in disease resistance under diet-restriction suggests that females might allocate resources toward immunity during development if they expect harsh environmental conditions as an adult or it might suggest that females allocate resources toward other life history activities (i.e. reproduction when food availability increases. We do not know what immune effectors were altered under diet-restriction to increase disease resistance, but our findings suggest that increased immune function might provide an explanation for the sexually-dimorphic increase in longevity generally observed in diet-restricted animals.

  17. Are generic and disease-specific health related quality of life correlated? The case of chronic lung disease due to sulfur mustard

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2009-09-01

    Full Text Available

    • BACKGROUND: The aim of this study was to investigate the association between the two most commonly used generic and disease specific health-related quality of life (HRQoL measures in patients with chronic lung disease due to SM: Medical Outcomes Study Short Form 36-Item (SF-36 and St George's Respiratory Questionnaire (SGRQ.
    • METHODS: This is a secondary analysis of Iranian Chemical Warfare Victims Health Assessment Study (ICWVHAS during October 2007 in Isfahan, Iran. In that survey, conducted in an outpatient setting, 292 patients with chronic lung disease due to SM were selected from all provinces in Iran. The total score and sub scores of correlations of SGRQ and SF-36 were assessed. Correlation of quality-of-life scores were evaluated using Pearson’s coefficient.
    • RESULTS: Samples were 276 patients who were selected for our analysis. No significant correlation was found between the total score or sub scores of SF-36 and the total score or sub scores of SGRQ (p > 0.05.
    • CONCLUSIONS: In patients with chronic lung disease due to SM, the SF-36 and SGRQ assess different aspects of HRQoL. Therefore applying both of them together, at least in the research setting is suggested.
    • KEYWORDS: Chronic Lung Disease, Health Related Quality of Life, Generic Health Related Quality of Life, Disease Specific Health Related Quality of Life, Sulfur Mustard.

  18. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles.

    Science.gov (United States)

    Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P; Castón, José R; Blanco, Esther; Alejo, Alí

    2015-09-24

    In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particles (VLPs). Our results further confirmed the differential antigenic properties exhibited by RHDV and RHDV2, highlighting the need of using RHDV2-specific diagnostic assays to monitor the spread of this new virus.

  19. NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ

    DEFF Research Database (Denmark)

    Karosiene, Edita; Rasmussen, Michael; Blicher, Thomas

    2013-01-01

    Major histocompatibility complex class II (MHCII) molecules play an important role in cell-mediated immunity. They present specific peptides derived from endosomal proteins for recognition by T helper cells. The identification of peptides that bind to MHCII molecules is therefore of great importa......MHCIIpan-3.0 method is the first pan-specific predictor covering all HLA class II molecules with known sequences including HLA-DR, HLA-DP, and HLA-DQ. The NetMHCpan-3.0 method is available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.0....

  20. Aspergillus specific IgE estimation by radioallergosorbent technique (RAST) in obstructive airways disease at Agra

    International Nuclear Information System (INIS)

    Sharma, S.K.; Singh, R.; Mehrotra, M.P.; Patney, N.L.; Sachan, A.S.; Shiromany, A.

    1986-01-01

    The radioallergosorbent technique (RAST) was used to measure the levels of Aspergillus specific IgE in 25 normal controls, 25 cases of extrinsic bronchial asthma and 25 cases of allergic broncho-pulmonary aspergillosis with a view to study the clinical role and its correlation with sputum culture, skin sensitivity and severity of airways obstruction. The test was performed using Pharmacia diagnostic kits with antigen derived from Aspergillus fumigatus. Abnormal levels of Aspergillus specific IgE were observed in 84 per cent cases of bronchial asthma but none of the controls. 86.7 per cent of all cases with positive skin test had positive radioallergosorbent test and there was no false positive reaction. There was a positive correlation of Aspergillus specific IgE with skin test positivity and with FEV 1 /FVC per cent. (author)

  1. The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS).

    Science.gov (United States)

    Alwan, Sura; Chambers, Christina D; Armenti, Vincent T; Sadovnick, A Dessa

    2015-01-01

    Multiple sclerosis (MS) is the most commonly acquired neurological disorder affecting young adults of reproductive age with an approximately 3:1 female to male ratio. Although pregnancy is not contraindicated in MS, data are limited regarding pregnancy outcome among MS patients, and the safety or risk to the fetus associated with most maternal MS treatments, such as disease modifying therapies (DMTs), during pregnancy is unknown. We review available epidemiological and registry data on MS and pregnancy and discuss the need to initiate a North American Multiple Sclerosis Pregnancy Registry that will prospectively identify pregnancies in women with MS, obtain information on the disease, and its treatment during gestation and lactation and follow the children to determine their health status. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Fifteen new risk loci for coronary artery disease highlight arterial wall-specific mechanisms

    OpenAIRE

    Howson, Joanna M.M.; Zhao, Wei; Barnes, Daniel R.; Ho, Weang-Kee; Young, Robin; Paul, Dirk S.; Waite, Lindsay L.; Freitag, Daniel F.; Fauman, Eric B.; Salfati, Elias L.; Sun, Benjamin B.; Eicher, John D.; Johnson, Andrew D.; Sheu, Wayne H.H.; Nielsen, Sune F.

    2017-01-01

    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier G...

  3. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

    OpenAIRE

    Howson, Joanna McCammond; Zhao, W; Barnes, Daniel Robert; Ho, W-K; Young, R; Paul, Dirk Stefan; Waite, LL; Freitag, DF; Fauman, EB; Salfati, EL; Sun, Benjamin; Eicher, JD; Johnson, AD; Sheu, WHH; Nielsen, SF

    2017-01-01

    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier G...

  4. Patient-specific factors influence somatic variation patterns in von Hippel?Lindau disease renal tumours

    OpenAIRE

    Fei, Suzanne S.; Mitchell, Asia D.; Heskett, Michael B.; Vocke, Cathy D.; Ricketts, Christopher J.; Peto, Myron; Wang, Nicholas J.; S?nmez, Kemal; Linehan, W. Marston; Spellman, Paul T.

    2016-01-01

    Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel?Lindau disease are at risk of developing multiple...

  5. Gender-based differences and menstrual cycle-related changes in specific diseases: implications for pharmacotherapy.

    Science.gov (United States)

    Ensom, M H

    2000-05-01

    Pharmacists should be aware of gender-based differences and menstrual cycle-related changes in six diseases: asthma, arthritis, migraine, diabetes, depression, and epilepsy. In general, women report symptoms of physical illness at higher rates, visit physicians more frequently, and make greater use of other health care services than men. Whereas reasons for these gender differences are not fully clear, a combination of biologic, physiologic, social, behavioral, psychologic, and cultural factors most likely contributes. A significant percentage of women with asthma, arthritis, migraine, diabetes, depression, or epilepsy experience worsening of their disease premenstrually. The mechanism is unknown, but is speculated to be multifactorial because of many endogenous and exogenous modulators and mediators of each disease. As part of general therapy for cycle-related exacerbations of any one of these disorders, patients should be encouraged to use a menstrual calendar to track signs and symptoms for two to three cycles; if cyclic trends are identified, the women should anticipate exacerbations and avoid triggering factors. Cyclic modulation with pharmacotherapy may be attempted. If unsuccessful, a trial of medical ovulation suppression with a gonadotropin-releasing hormone (GnRH) analog may be warranted. If that is successful, continuous therapy with a GnRH analog and steroid add-back therapy or less expensive alternatives may be effective. If pharmacotherapy is impractical, hysterectomy and bilateral oophorectomy with estrogen replacement therapy is a last resort. Gender differences and menstrual cycle-related changes are important areas for clinical and mechanistic research.

  6. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Directory of Open Access Journals (Sweden)

    Qiu Z

    2013-07-01

    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  7. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles

    OpenAIRE

    Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P.; Castón, José R.; Blanco, Esther; Alejo, Alí

    2015-01-01

    International audience; In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particl...

  8. The Comparison of WHOQOL-BREF with Disease Specific Heath Related Quality of Life Questionnaire in Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    M. Biglari

    2015-11-01

    Full Text Available Irritable Bowel Syndrome (IBS is one of the most common gastrointestinal disorders particularly affecting the quality of life (QOL. Evaluating QOL in IBS patients is a valuable method of defining a psychobiological pattern of disease. Various disease specific and general instruments are now available to measure health-related QOL (HRQOL in IBS patients. Though, no comparison has been made between these tools especially in non-western countries. We aimed to compare QOL measures between two specific and general QOL questionnaires in a sample of Iranian IBS patients. A total of 250 IBS patients were diagnosed based on Rome III criteria (mean age 29.6 ± 9.6 years. HRQOL was assessed using disease specific quality of life for IBS (IBS-QOL and generic World Health Organization Quality of Life-BREF (WHOQOL-BREF questionnaires. Patients also completed Speilberger`s “State/Trait Anxiety Inventory” and “Beck Depression Inventory-II” for the evaluation of anxiety and depression symptoms. The severity of symptoms was independently associated with HRQOL in patients using WHOQOL-BREF and IBS-QOL (r = -0.48 and -0.39 respectively, P P value < 0.001. Controlling for anxiety and depression symptoms did not influence the strength of observed correlation. The WHOQOL-BREF is a psychometrically sound, rapid and convenient instrument whose HRQOL measure is as valid and accurate as the disease-specific IBS-QOL questionnaire. It seems reasonable to use the WHOQOL-BREF alongside the IBS-QOL.

  9. The Comparison of WHOQOL-BREF with Disease Specific Heath Related Quality of Life Questionnaire in Irritable Bowel Syndrome.

    Science.gov (United States)

    Jamali, Raika; Biglari, Mohammad

    2015-11-01

    Irritable Bowel Syndrome (IBS) is one of the most common gastrointestinal disorders particularly affecting the quality of life (QOL). Evaluating QOL in IBS patients is a valuable method of defining a psychobiological pattern of disease. Various disease specific and general instruments are now available to measure health-related QOL (HRQOL) in IBS patients. Though, no comparison has been made between these tools especially in non-western countries. We aimed to compare QOL measures between two specific and general QOL questionnaires in a sample of Iranian IBS patients. A total of 250 IBS patients were diagnosed based on Rome III criteria (mean age 29.6 ± 9.6 years). HRQOL was assessed using disease specific quality of life for IBS (IBS-QOL) and generic World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaires. Patients also completed Speilberger`s "State/Trait Anxiety Inventory" and "Beck Depression Inventory-II" for the evaluation of anxiety and depression symptoms. The severity of symptoms was independently associated with HRQOL in patients using WHOQOL-BREF and IBS-QOL (r = -0.48 and -0.39 respectively, P < 0.001). In linear regression analysis, a strong correlation was observed between the HRQOL scores of IBS-QOL and the WHOQOL-BREF questionnaires (standard β = 0.86 (95%CI: 1.15 - 1.44), P value < 0.001). Controlling for anxiety and depression symptoms did not influence the strength of observed correlation. The WHOQOL-BREF is a psychometrically sound, rapid and convenient instrument whose HRQOL measure is as valid and accurate as the disease-specific IBS-QOL questionnaire. It seems reasonable to use the WHOQOL-BREF alongside the IBS-QOL.

  10. Differences in Disease-specific Quality of Life in Patients with Actinic Keratosis in Australia and Denmark.

    Science.gov (United States)

    Miller, Iben Marie; Vinding, Gabrielle; Zarchi, Kian; Esmann, Solveig; Murrell, Dedee F; Jemec, Gregor B

    2016-04-01

    Actinic keratosis (AK) negatively influences patient quality of life as measured by the disease-specific Actinic Keratosis Quality of Life (AKQoL) questionnaire. The quality of life in Australian patients was significantly less affected than in Danish patients. We hypothesize that general factors such as public awareness and cultural connotations of AK, may influence the impact of AK on quality of life (QoL).

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    AIM: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development......, the data of calculated daily macro- and micronutrient intake do not suggest any explicit influence of gender-specific nutrition in the development of ALD....

  12. The effects of infographics and several quantitative versus qualitative formats for cardiovascular disease risk, including heart age, on people's risk understanding.

    NARCIS (Netherlands)

    Damman, Olga C; Vonk, Suzanne I; Van den Haak, Maaike J; van Hooijdonk, Charlotte M J; Timmermans, Danielle R M

    2018-01-01

    To study how comprehension of cardiovascular disease (CVD) risk is influenced by: (1) infographics about qualitative risk information, with/without risk numbers; (2) which qualitative risk dimension is emphasized; (3) heart age vs. traditional risk format.

  13. Association between TSH-Receptor Autoimmunity, Hyperthyroidism, Goitre, and Orbitopathy in 208 Patients Included in the Remission Induction and Sustenance in Graves' Disease Study

    DEFF Research Database (Denmark)

    Laurberg, Peter; Nygaard, Birte; Andersen, Stig

    2014-01-01

    Background. Graves' disease may have a number of clinical manifestations with varying degrees of activity that may not always run in parallel. Objectives. To study associations between serum levels of TSH-receptor autoantibodies and the three main manifestations of Graves' disease (hyperthyroidism...... and Sustenance in Graves' Disease (RISG)." Patients were systematically tested for degree of biochemical hyperthyroidism, enlarged thyroid volume by ultrasonography, and the presence of orbitopathy. Results. Positive correlations were found between the levels of TSH-receptor autoantibodies in serum and the three...... manifestations of Graves' disease: severeness of hyperthyroidism, presence of enlarged thyroid, and presence of orbitopathy, as well as between the different types of manifestations. Only around half of patients had enlarged thyroid gland at the time of diagnosis of hyperthyroidism, whereas 25-30% had...

  14. Models of simulation and prediction of the behavior of dengue in four Colombian cities, including climate like modulating variable of the disease

    International Nuclear Information System (INIS)

    Garcia Giraldo, Jairo A; Boshell, Jose Francisco

    2004-01-01

    ARIMA-type models are proposed to simulate the behavior of dengue and to make apparent the relations with the climatic variability in four localities of Colombia. The climatic variable was introduced into the models as an index that modulates the behavior of the disease. It was obtained by means of a multivariate analysis of principal components. The investigation was carried out with information corresponding to the epidemiological weeks from January 1997 to December 2000, for both the number of disease cases and the data corresponding to the meteorological variables. The study shows that the variations of the climate between the previous 9 to 14 weeks have influence on the appearance of new cases of dengue. In particular, the precipitation in these weeks was seen to be greater when in later periods the disease presented epidemic characteristics than the precipitation in those weeks preceded the disease within endemic limits

  15. An Energy efficient application specific integrated circuit for electrocardiogram feature detection and its potential for ambulatory cardiovascular disease detection.

    Science.gov (United States)

    Jain, Sanjeev Kumar; Bhaumik, Basabi

    2016-03-01

    A novel algorithm based on forward search is developed for real-time electrocardiogram (ECG) signal processing and implemented in application specific integrated circuit (ASIC) for QRS complex related cardiovascular disease diagnosis. The authors have evaluated their algorithm using MIT-BIH database and achieve sensitivity of 99.86% and specificity of 99.93% for QRS complex peak detection. In this Letter, Physionet PTB diagnostic ECG database is used for QRS complex related disease detection. An ASIC for cardiovascular disease detection is fabricated using 130-nm CMOS high-speed process technology. The area of the ASIC is 0.5 mm(2). The power dissipation is 1.73 μW at the operating frequency of 1 kHz with a supply voltage of 0.6 V. The output from the ASIC is fed to their Android application that generates diagnostic report and can be sent to a cardiologist through email. Their ASIC result shows average failed detection rate of 0.16% for six leads data of 290 patients in PTB diagnostic ECG database. They also have implemented a low-leakage version of their ASIC. The ASIC dissipates only 45 pJ with a supply voltage of 0.9 V. Their proposed ASIC is most suitable for energy efficient telemetry cardiovascular disease detection system.

  16. Mapping the author gender-distribution of disease-specific medical research

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, J.P.; Schneider, J.W.; Nielsen, M.W.

    2016-07-01

    This short paper responds to a recent call for attention to the “diversity challenge” in biomedical research, specifically with regard to gender diversity. The lack of diversity can be limiting for the progression of knowledge production, a viewpoint shared by both the European Commission, the League of European Research Universities and the National Institute of Health. (Author)

  17. Quantification of specific E. coli in gut mucosa from Crohn's disease patients

    DEFF Research Database (Denmark)

    Jensen, Stina Rikke; Fink, Lisbeth Nielsen; Struve, Carsten

    2011-01-01

    We here present a method based on qRT-PCR to quantify E. coli LF82 in intestinal human samples. Two different primer-probe sets were designed to detect LF82, and a third to target total E. coli. The assay showed high robustness and specificity for detection of LF82 in the presence of intestinal...

  18. Characterisation of CD4 T cells in healthy and diseased koalas (Phascolarctos cinereus) using cell-type-specific monoclonal antibodies.

    Science.gov (United States)

    Mangar, Chandan; Armitage, Charles W; Timms, Peter; Corcoran, Lynn M; Beagley, Kenneth W

    2016-07-01

    The koala (Phascolarctos cinereus) is an arboreal herbivorous marsupial that is an Australian icon. Koalas in many parts of Australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as Chlamydia spp. and the koala retrovirus (KoRV), which may contribute to the incidence of lymphoma and leukaemia in this species. Due to a lack of koala-specific immune reagents and assays there is currently no way to adequately analyse the immune response in healthy, diseased or vaccinated animals. This paper reports the production and characterisation of the first anti-koala CD4 monoclonal antibody (mAb). The koala CD4 gene was identified and used to develop recombinant proteins for mAb production. Fluorochrome-conjugated anti-CD4 mAb was used to measure the levels of CD4(+) lymphocytes collected from koala spleens (41.1%, range 20-45.1%) lymph nodes (36.3%, range 19-55.9%) and peripheral blood (23.8%, range 17.3-35%) by flow cytometry. Biotin-conjugated anti-CD4 mAb was used for western blot to determine an approximate size of 52 kDa for the koala CD4 molecule and used in immunohistochemistry to identify CD4(+) cells in the paracortical region and germinal centres of spleen and lymph nodes. Using the anti-CD4 mab we showed that CD4 cells from vaccinated, but not control, koalas proliferated following in vitro stimulation with UV-inactivated Chlamydia pecorum and recombinant chlamydial antigens. Since CD4(+) T cells have been shown to play a pivotal role in clearing chlamydial infection in both human and mouse infections, using this novel antibody will help determine the role CD4(+) T cells play in protection against chlamydial infection in koalas and also enhance our knowledge of how KoRV affects the koala immune system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases.

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    David Wong

    Full Text Available BACKGROUND: Dermatomyositis (DM is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood. METHODOLOGY AND FINDINGS: We analyzed genome-wide expression data in DM skin and compared them to those from healthy controls. We observed a robust upregulation of interferon (IFN-inducible genes in DM skin, as well as several other gene modules pertaining to inflammation, complement activation, and epidermal activation and differentiation. The interferon (IFN-inducible genes within the DM signature were present not only in DM and lupus, but also cutaneous herpes simplex-2 infection and to a lesser degree, psoriasis. This IFN signature was absent or weakly present in atopic dermatitis, allergic contact dermatitis, acne vulgaris, systemic sclerosis, and localized scleroderma/morphea. We observed that the IFN signature in DM skin appears to be more closely related to type I than type II IFN based on in vitro IFN stimulation expression signatures. However, quantitation of IFN mRNAs in DM skin shows that the majority of known type I IFNs, as well as IFN g, are overexpressed in DM skin. In addition, both IFN-beta and IFN-gamma (but not other type I IFN transcript levels were highly correlated with the degree of the in vivo IFN transcriptional response in DM skin. CONCLUSIONS AND SIGNIFICANCE: As in the blood and muscle, DM skin is characterized by an overwhelming presence of an IFN signature, although it is difficult to conclusively define this response as type I or type II. Understanding the significance of the IFN signature in this wide array of inflammatory diseases will be furthered by identification of the nature of the cells that both produce and respond to IFN, as well as which IFN subtype is biologically active in each diseased tissue.

  20. The accuracy of chest radiographs in the detection of congenital heart disease and in the diagnosis of specific congenital cardiac lesions

    International Nuclear Information System (INIS)

    Laya, Bernard F.; Goske, Marilyn J.; Morrison, Stuart; Reid, Janet R.; Swischuck, Leonard; Ey, Elizabeth H.; Murphy, Daniel J.; Lieber, Michael; Obuchowski, Nancy

    2006-01-01

    Congenital heart disease (CHD) is a significant cause of morbidity and mortality in pediatric patients. Traditional teaching holds that specific types of CHD can be diagnosed on the chest radiograph (CXR) through pattern recognition. To determine the accuracy of radiologists in detecting CHD on the CXR. This study was a blinded retrospective review of chest radiographs from 281 patients (<12 years) by five pediatric radiologists from three institutions. Thirteen groups were evaluated that included 12 categories of CHD and a control group of patients without heart disease. Radiographs were assessed for heart size, heart and mediastinal shape and vascularity. Clinical information, angiography, echocardiograms and surgery were used as the gold standard for definitive diagnosis. The average accuracy of the five readers in distinguishing normal from CHD patients was 78% (range of 72% to 82%). The overall measure of accuracy in distinguishing specific congenital cardiac lesions among 13 groups of patients was 71% (range of 63% to 79%). CXR alone is not diagnostic of specific cardiac lesions, with a low accuracy of only 71%. We believe that less emphasis should be placed on the use of radiographs alone in diagnosing specific congenital cardiac lesions. (orig.)

  1. Association of Kidney Disease Measures with Cause-Specific Mortality: The Korean Heart Study.

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    Yejin Mok

    Full Text Available The link of low estimated glomerular filtration rate (eGFR and high proteinuria to cardiovascular disease (CVD mortality is well known. However, its link to mortality due to other causes is less clear.We studied 367,932 adults (20-93 years old in the Korean Heart Study (baseline between 1996-2004 and follow-up until 2011 and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases, cancer (4,035 cases, and other (non-CVD/non-cancer causes (3,152 cases after adjusting for potential confounders.Although cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD, non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR <60 ml/min/1.73 m2 and 54.3% for proteinuria ≥1+. Lower eGFR (<60 vs. ≥60 ml/min/1.73 m2 was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24-1.78] and non-CVD/non-cancer causes (1.78 [1.54-2.05]. The risk of cancer mortality only reached significance at eGFR <45 ml/min/1.73 m2 when eGFR 45-59 ml/min/1.73 m2 was set as a reference (1.62 [1.10-2.39]. High proteinuria (dipstick ≥1+ vs. negative/trace was consistently associated with mortality due to CVD (1.93 [1.66-2.25], cancer (1.49 [1.32-1.68], and other causes (2.19 [1.96-2.45]. Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis.Low eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD

  2. Disease-in-a-dish: the contribution of patient-specific induced pluripotent stem cell technology to regenerative rehabilitation.

    Science.gov (United States)

    Mack, David L; Guan, Xuan; Wagoner, Ashley; Walker, Stephen J; Childers, Martin K

    2014-11-01

    Advances in regenerative medicine technologies will lead to dramatic changes in how patients in rehabilitation medicine clinics are treated in the upcoming decades. The multidisciplinary field of regenerative medicine is developing new tools for disease modeling and drug discovery based on induced pluripotent stem cells. This approach capitalizes on the idea of personalized medicine by using the patient's own cells to discover new drugs, increasing the likelihood of a favorable outcome. The search for compounds that can correct disease defects in the culture dish is a conceptual departure from how drug screens were done in the past. This system proposes a closed loop from sample collection from the diseased patient, to in vitro disease model, to drug discovery and Food and Drug Administration approval, to delivering that drug back to the same patient. Here, recent progress in patient-specific induced pluripotent stem cell derivation, directed differentiation toward diseased cell types, and how those cells can be used for high-throughput drug screens are reviewed. Given that restoration of normal function is a driving force in rehabilitation medicine, the authors believe that this drug discovery platform focusing on phenotypic rescue will become a key contributor to therapeutic compounds in regenerative rehabilitation.

  3. Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

    Science.gov (United States)

    Matsushita, Takashi; Hasegawa, Minoru; Matsushita, Yukiyo; Echigo, Takeshi; Wayaku, Takamasa; Horikawa, Mayuka; Ogawa, Fumihide; Takehara, Kazuhiko; Sato, Shinichi

    2007-02-01

    Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

  4. Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

    Science.gov (United States)

    Maddula, Surekha; Ansell, Jack

    2013-08-01

    The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

  5. Gender specific differences in peripheral artery disease and their impact on cardiovascular rehabilitation -the experience of a Romanian Rehabilitation Hospital

    Directory of Open Access Journals (Sweden)

    Horațiu Comșa

    2018-02-01

    Full Text Available Introduction. As the prevalence of peripheral artery disease (PAD is increasing in developing countries, so are the healthcare and socio-economic costs it brings about. This particular form of atherosclerotic disease is very much age-dependent, and along with the increase in life-expectancy, the lasts decades have seen a sharp rise in PAD prevalence in women. Knowledge regarding gender-specific aspects of the disease are scarce. This has a negative effect on overall outcomes of female PAD patients. Aim. This research aimed to identify gender peculiarities of PAD and evaluate their impact on cardiovascular rehabilitation. Material and methods. This was a retrospective observational study of 104 PAD patients (73 men and 31 women admitted in 2016 to the Cardiology department of the Rehabilitation Hospital Cluj-Napoca. Demographic, clinical and biological parameters were recorded, as well as the treatment/rehabilitation regimens prescribed. The subjects were divided into to groups according to gender. Statistical analysis was done using the student t-test for unequal variances, hi-square test and the stepwise method for multivariate analysis. Results. The female group had a higher prevalence of diabetes mellitus (45% vs 33%, p=ns, but men were more likely smokers (74% vs 51%- p=0.017. Women had higher median total cholesterol values (p=0.006 and lower HDL-cholesterol levels (p=0.033. More than half of the female patients were already experiencing symptoms of critical limb ischemia on admission (57%, while intermittent claudication was predominant with men (66%. Multivariate analysis identified identified female gender (p=0.028 and ABI (p<0.0001 as sole independent predictors for the severity of the disease. Revascularization using percutaneous techniques was the preferred option for women (35% vs 27%, while surgery was performed more often in men (38% vs 29%- p=ns. Home-based exercise training was indicated on discharge for more than half of the

  6. Association between TSH-Receptor Autoimmunity, Hyperthyroidism, Goitre, and Orbitopathy in 208 Patients Included in the Remission Induction and Sustenance in Graves’ Disease Study

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    Peter Laurberg

    2014-01-01

    Full Text Available Background. Graves’ disease may have a number of clinical manifestations with varying degrees of activity that may not always run in parallel. Objectives. To study associations between serum levels of TSH-receptor autoantibodies and the three main manifestations of Graves’ disease (hyperthyroidism, goiter, and presence of orbitopathy at the time of diagnosis of hyperthyroidism. Methods. We describe a cohort of 208 patients with newly diagnosed Graves’ hyperthyroidism. Patients were enrolled in a multiphase study of antithyroid drug therapy of Graves’ hyperthyroidism, entitled “Remission Induction and Sustenance in Graves’ Disease (RISG.” Patients were systematically tested for degree of biochemical hyperthyroidism, enlarged thyroid volume by ultrasonography, and the presence of orbitopathy. Results. Positive correlations were found between the levels of TSH-receptor autoantibodies in serum and the three manifestations of Graves’ disease: severeness of hyperthyroidism, presence of enlarged thyroid, and presence of orbitopathy, as well as between the different types of manifestations. Only around half of patients had enlarged thyroid gland at the time of diagnosis of hyperthyroidism, whereas 25–30% had orbitopathy. Conclusions. A positive but rather weak correlation was found between TSH-receptor antibodies in serum and the major clinical manifestation of Graves’ disease. Only half of the patients had an enlarged thyroid gland at the time of diagnosis.

  7. Age-specific and sex-specific mortality in 187 countries, 1970-2010: a systematic analysis for the Global Burden of Disease Study 2010.

    Science.gov (United States)

    Wang, Haidong; Dwyer-Lindgren, Laura; Lofgren, Katherine T; Rajaratnam, Julie Knoll; Marcus, Jacob R; Levin-Rector, Alison; Levitz, Carly E; Lopez, Alan D; Murray, Christopher J L

    2012-12-15

    Estimation of the number and rate of deaths by age and sex is a key first stage for calculation of the burden of disease in order to constrain estimates of cause-specific mortality and to measure premature mortality in populations. We aimed to estimate life tables and annual numbers of deaths for 187 countries from 1970 to 2010. We estimated trends in under-5 mortality rate (children aged 0-4 years) and probability of adult death (15-59 years) for each country with all available data. Death registration data were available for more than 100 countries and we corrected for undercount with improved death distribution methods. We applied refined methods to survey data on sibling survival that correct for survivor, zero-sibling, and recall bias. We separately estimated mortality from natural disasters and wars. We generated final estimates of under-5 mortality and adult mortality from the data with Gaussian process regression. We used these results as input parameters in a relational model life table system. We developed a model to extrapolate mortality to 110 years of age. All death rates and numbers have been estimated with 95% uncertainty intervals (95% UIs). From 1970 to 2010, global male life expectancy at birth increased from 56·4 years (95% UI 55·5-57·2) to 67·5 years (66·9-68·1) and global female life expectancy at birth increased from 61·2 years (60·2-62·0) to 73·3 years (72·8-73·8). Life expectancy at birth rose by 3-4 years every decade from 1970, apart from during the 1990s (increase in male life expectancy of 1·4 years and in female life expectancy of 1·6 years). Substantial reductions in mortality occurred in eastern and southern sub-Saharan Africa since 2004, coinciding with increased coverage of antiretroviral therapy and preventive measures against malaria. Sex-specific changes in life expectancy from 1970 to 2010 ranged from gains of 23-29 years in the Maldives and Bhutan to declines of 1-7 years in Belarus, Lesotho, Ukraine, and Zimbabwe

  8. Population-specific association between ABCG2 variants and tophaceous disease in people with gout.

    Science.gov (United States)

    He, Wendy; Phipps-Green, Amanda; Stamp, Lisa K; Merriman, Tony R; Dalbeth, Nicola

    2017-03-07

    Tophi contribute to musculoskeletal disability, joint damage and poor health-related quality of life in people with gout. The aim of this study was to examine the role of SLC2A9 and ABCG2 variants in tophaceous disease in people with gout. Participants (n = 1778) with gout fulfilling the 1977 American Rheumatism Association (ARA) classification criteria, who were recruited from primary and secondary care, attended a detailed study visit. The presence of palpable tophi was recorded. SLC2A9 rs11942223, ABCG2 rs2231142 and ABCG2 rs10011796 were genotyped. Data were analysed according to tophus status. Compared to participants without tophi, those with tophi were older, had longer disease duration and higher serum creatinine, and were more likely to be of Māori or Pacific (Polynesian) ancestry. SLC2A9 rs11942223 was not associated with tophi. However, the risk alleles for both ABCG2 single nucleotide polymorphisms (SNPs) were present more frequently in those with tophi (OR (95% CI) 1.24 (1.02-1.51) for rs2231142 and 1.33 (1.01-1.74) for rs10011796, p gout.

  9. The specific features of using a rivastigmine transdermal formulation in Alzheimer’s disease

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    Elena Evgenyevna Vasenina

    2012-01-01

    Full Text Available Cholinergic deficiency associated mainly with the degeneration of neurons in the nucleus basalis of Meynert is one of the key factors of the development of cognitive impairments in Alzheimer’s disease (AD. Cholinesterase inhibitors are used to treat mild and moderate dementia in AD. However, the wide use of this group of agents is limited by the high incidence of some side effects. The application of a novel rivastigmine transdermal (patch formulation substantially reduces the risk of adverse reactions chiefly associated with a negative effect on the gastrointestinal tract and increases treatment adherence. Thus, there is a rise in the number of patients who may be given the drug in the optimal therapeutic dose for a long time.

  10. Specific features of red blood cell morphology in hemolytic disease neonates undergoing intrauterine intravascular blood transfusion

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    A. V. Ivanova

    2016-01-01

    Full Text Available The paper presents data on the characteristics of red blood cell morphology in infants who have undergone intrauterine intravascular blood transfusion for hemolytic disease of the fetus. The infants are shown to have a reduction in the mean volume of red blood cells and in their mean level of hemoglobin, a decrease in the fraction of fetal hemoglobin and an increase in oxygen tension at half saturation. The above morphological characteristics of red blood cells remain decreased during the neonatal period after exchange transfusion or others, as clinically indicated, which seems to suggest that the compensatory-adaptive mechanisms to regulate hematopoiesis are exhausted and a donor’s red blood cells continue to be predominant.

  11. Interrelation specific autoimmune pathologies of a thyroid gland with inorganic autoimmune rheumatic diseases

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    O V Paramonova

    2012-03-01

    Full Text Available The problem of a pathology of a thyroid gland at rheumatic diseases, in particular at rheumatoid arthritis, remains actual and to this day. The work purpose was studying antitelogenesis to thyroid hormones at patients with mixt autoimmune pathology. In whey of blood of patients with RA and autothyroid pathology are found out antibodies (AB to Т3 and Т4, their concentration correlates with activity of pathological process. It is shown, that level AB to Т3 and Т4 authentically differs from the maintenance of the given antibodies in whey of blood of healthy faces. Level of antibodies to thyroid hormones can be considered as the criterion predicting development of pathology of a thyroid gland at patients with RA.

  12. Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT)

    DEFF Research Database (Denmark)

    Schou Karlsen, Nikoline Marie; Karlsen, Mona Aarenstrup; Høgdall, Estrid

    2016-01-01

    .1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour...... presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. CONCLUSIONS...

  13. Keeping health facilities safe: one way of strengthening the interaction between disease-specific programmes and health systems.

    Science.gov (United States)

    Harries, Anthony D; Zachariah, Rony; Tayler-Smith, Katie; Schouten, Erik J; Chimbwandira, Frank; Van Damme, Wim; El-Sadr, Wafaa M

    2010-12-01

    The debate on the interaction between disease-specific programmes and health system strengthening in the last few years has intensified as experts seek to tease out common ground and find solutions and synergies to bridge the divide. Unfortunately, the debate continues to be largely academic and devoid of specificity, resulting in the issues being irrelevant to health care workers on the ground. Taking the theme 'What would entice HIV- and tuberculosis (TB)-programme managers to sit around the table on a Monday morning with health system experts', this viewpoint focuses on infection control and health facility safety as an important and highly relevant practical topic for both disease-specific programmes and health system strengthening. Our attentions, and the examples and lessons we draw on, are largely aimed at sub-Saharan Africa where the great burden of TB and HIV ⁄ AIDS resides, although the principles we outline would apply to other parts of the world as well. Health care infections, caused for example by poor hand hygiene, inadequate testing of donated blood, unsafe disposal of needles and syringes, poorly sterilized medical and surgical equipment and lack of adequate airborne infection control procedures, are responsible for a considerable burden of illness amongst patients and health care personnel, especially in resource-poor countries. Effective infection control in a district hospital requires that all the components of a health system function well: governance and stewardship, financing,infrastructure, procurement and supply chain management, human resources, health information systems, service delivery and finally supervision. We argue in this article that proper attention to infection control and an emphasis on safe health facilities is a concrete first step towards strengthening the interaction between disease-specific programmes and health systems where it really matters – for patients who are sick and for the health care workforce who provide

  14. Night shift work at specific age ranges and chronic disease risk factors

    Science.gov (United States)

    Ramin, Cody; Devore, Elizabeth E; Wang, Weike; Pierre-Paul, Jeffrey; Wegrzyn, Lani R; Schernhammer, Eva S

    2014-01-01

    Objectives We examined the association of night shift work history and age when night shift work was performed with cancer and cardiovascular disease risk factors among 54 724 women in the Nurses' Health Study (NHS) II. Methods We calculated age-adjusted and socioeconomic status-adjusted means and percentages for cancer and cardiovascular risk factors in 2009 across categories of night shift work history. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for key risk factors among 54 724 participants (72% ever shift workers). We further examined these associations by age (20–25, 26–35, 36– 45 and 46+ years) at which shift work was performed. Results Ever night shift workers had increased odds of obesity (body mass index ≥30 kg/m2; OR=1.37, 95% CI 1.31 to 1.43); higher caffeine intake (≥131 mg/day; OR=1.16, 95% CI 1.12 to 1.22) and total calorie intake (≥1715 kcal/day; OR=1.09, 95% CI 1.04 to 1.13); current smoking (OR=1.30, 95% CI 1.19 to 1.42); and shorter sleep durations (≤7 h of sleep/day; OR=1.19, 95% CI 1.15 to 1.24) compared to never night shift workers. These estimates varied depending on age at which night work was performed, with a suggestion that night shift work before age 25 was associated with fewer risk factors compared to night shift work at older ages. Conclusions Our results indicate that night shift work may contribute to an adverse chronic disease risk profile, and that risk factors may vary depending on the age at which night shift work was performed. PMID:25261528

  15. Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Nakatani, E; Kanatani, Y; Kaneda, H; Nagai, Y; Teramukai, S; Nishimura, T; Zhou, B; Kojima, S; Kono, H; Fukushima, M; Kitamoto, T; Mizusawa, H

    2016-09-01

    Akinetic mutism is thought to be an appropriate therapeutic end-point in patients with sporadic Creutzfeldt-Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset. The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms. Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14-1.99, and HR 2.15, 95% CI1.61-2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance. The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease. © 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  16. Screening of potential medicinal plants from District Sawat specific for controlling women diseases

    International Nuclear Information System (INIS)

    Sarwat, A.; Shinwari, Z.K.; Ahmad, N.

    2012-01-01

    Ethnobotany provides a scientific rationale to identify medicinally important plant species, especially for finding new drugs that play vital role in the treatment of different diseases. This ethnobotanical survey of Swat, Khyber Pakhtunkhwa (KP) was carried out to identify medicinally important plant species that are traditionally used to treat gynecological disorders and infectious diseases, and to study their antimicrobial potential against pathogens that cause infections in females. The antimicrobial activities were investigated using the well diffusion method against four different bacterial strains and one fungal strain. Results showed that out of 12 plants studied, seven plants exhibited inhibitory effects against Candida albicans, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli. Woodfordia fruticosa, Quercus dilatata, Erythrina variegata, Ficus religiosa and Berberis lycium showed high antifungal activity against C. albicans with minimum inhibitory concentration (MIC) values of 2.5, 1.25, 0.625, 1.25, 0.3125 mg/ml and minimum bactericidal concentration (MBC) values of 5, 2.5, 1.25, 2.5, 0.625 mg/ml, respectively. Both Woodfordia fruticosa and Quercus dilatata showed antimicrobial potential against E. coli and K. pneumoniae with similar MIC values of 2.5 mg/ml and MBC values of 5 mg/ml. Plants exhibiting inhibitory potential against S. aureus were Woodfordia fruticosa, Quercus dilatata, Azadirachta indica and Curcuma longa and all of them possessed similar MIC values of 5 mg/ml and MBC values of 2.5 mg/ml, respectively. None of the plants showed antimicrobial activity against Pseudomonas aeruginosa. Proximate analysis showed that in comparative assessment of the various species, Zanthoxylum alatum had the highest fat and energy values. (author)

  17. Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes.

    Science.gov (United States)

    Li, Qian; Luo, Changying; Luo, Chengjuan; Wang, Jianmin; Li, Benshang; Ding, Lixia; Chen, Jing

    2017-08-01

    Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20 × 10 8 /kg and 4.3 × 10 6 /kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18 days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5 months (range, 2-130 months), the overall survival in all patients was 95.8%. The incidence of grade II-III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

  18. Optimization of Time Controlled 6-mercaptopurine Delivery for Site- Specific Targeting to Colon Diseases.

    Science.gov (United States)

    Hude, Rahul U; Jagdale, Swati C

    2016-01-01

    6-MP has short elimination time (Mercaptopurine (6-MP) for treatment of colon diseases. Compression coating technique was used. 32 full factorial design was designed for optimization of the outer coat for the core tablet. For outer coat amount of Eudragit RS 100 and hydroxypropyl methylcellulose (HPMC K100) were employed as independent variables each at three levels while responses evaluated were swelling index and bursting time. Direct compression method was used for tablets formulation. 80% w/w of microcrystalline cellulose and 20% w/w of croscarmellose sodium were found to be optimum concentration for the core tablet. The outer coat of optimized batch (ED) contains 21.05% w/w Eudragit RS 100 and 78.95% w/w HPMC K100 of total polymer weight. In-vitro dissolution study indicated that combination of polymer retards the drug release in gastric region and releases ≥95% of drug in colonic region after ≥7 h. Whereas in case of in-vivo placebo x-ray imaging study had shown that the tablet reaches colonic part after 5±0.5 h providing the proof of arrival in the colon. Stability study indicated that the optimized formulation were physically and chemically stable. Present research work concluded that compression coating by Eudragit RS 100 and HPMC K100 to 6-MP core provides potential colon targeted system with advantages of reduced gastric exposure and enhanced bioavailability. Formulation can be considered as potential and promising candidate for the treatment of colon diseases.

  19. ROLE OF PREEXISTING VIRUS-SPECIFIC IgG IN PRIMARY DISEASE AND IN REINFECTION WITH RESPIRATORY SYNCYTIAL VIRUS

    Directory of Open Access Journals (Sweden)

    V. Z. Krivitskaya

    2012-01-01

    Full Text Available Abstract. The aim of the study is evaluation of links between presence in blood of specific pre-existing IgG to respiratory-syncytial virus (RSV, clinical course of RSV infection and character specific to RSV humoral immune response in patients of different ages. The antibodies were detected by ELISA using whole RS virus or synthetic peptides corresponded to the selected determinants of the envelope RSV proteins. It was shown that RS specific maternal IgG antibodies passively transferred to babies in utero can circulate in the blood up to 10 months of life. The analysis of paired sera of 45 babies in the age of 1–10 months revealed firstly that presence of maternal IgG specific antibodies to the conservative B-cell immunogenic determinants of the F-protein (amino acids 221–232 and/or the G-protein (amino acids 152–164 and 184–198 is coupled with more high morbidity of primary RSV infection (89% versus 56%, p = 0.023, and also with more high frequency of complicated by bronchus obstruction course of the disease (81% versus 20%, р = 0.001 in compare with babies who were serologically negative to the maternal determinants specific antibodies. The correlation analysis has shown that the high presence of maternal determinant-specific IgG in the blood in babies till 10 months of life is associated in the case of primary infection with disbalance of humoral anti-viral immune response: intensive synthesis of serum RSV IgA. This is evidence of complicated course of infection with simultaneous suppression of response to RSV specific IgG. As opposed to the primary RSV infection in patients older than 3 years (n = 121 it was not detected links between anamnestic determinant-specific IgG synthesized by own immune system as the results of previous disease episodes and synthesis of anti-RSV IgG, IgM, IgE and IgA in RSV re-infections. In the contrast to babies in more older patients the feedback connection between level of pre-existing determinant-specific

  20. Lyme Disease.

    Science.gov (United States)

    Taylor, George C.

    1991-01-01

    This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…

  1. Effects of dietary nucleotides on growth, non-specific immune response and disease resistance of sea cucumber Apostichopus japonicas.

    Science.gov (United States)

    Wei, Zehong; Yi, Lina; Xu, Wei; Zhou, Huihui; Zhang, Yanjiao; Zhang, Wenbing; Mai, Kangsen

    2015-11-01

    A 9-week feeding trial was conducted to investigate the effects of dietary nucleotides (NT) on growth, immune response and disease resistance of sea cucumber Apostichopus japonicas (initial weight: 5.87 ± 0.03 g). Four graded levels of dietary NT were designed as 0, 150, 375 and 700 mg/kg, respectively. After the feeding trial, sea cucumbers were challenged with Vibrio splendidus for the determination of disease resistance. The results showed that the specific growth rates were significantly higher in sea cucumber fed the diet with 375 mg/kg NT than those fed the basal diet without NT supplementation (P sea cucumber fed diets with nucleotides (≥ 375 mg/kg) had significantly higher phagocytic activities in coelomic fluid (P 0.05). After being challenged with V. splendidus, the cumulative mortalities of sea cucumber fed diets with 150 and 375 mg/kg NT were significantly lower than that in the treatment without dietary nucleotide supplementation (P sea cucumber in vivo. In conclusion, it was showed that dietary NT does increase the growth performance, non-specific immunity and disease resistance of sea cucumber. The optimum dietary NT supplementation level for sea cucumber was found to be 375 mg/kg. The application of dietary NT may present a novel strategy for health management in sea cucumber's aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Specific plasma oxylipins increase the odds of cardiovascular and cerebrovascular events in patients with peripheral artery disease.

    Science.gov (United States)

    Caligiuri, Stephanie P B; Aukema, Harold M; Ravandi, Amir; Lavallée, Renée; Guzman, Randy; Pierce, Grant N

    2017-08-01

    Oxylipins and fatty acids may be novel therapeutic targets for cardiovascular disease. The objective was to determine if plasma oxylipins or fatty acids can influence the odds of cardiovascular/cerebrovascular events. In 98 patients (25 female, 73 male) with peripheral artery disease, the prevalence of transient ischemic attacks, cerebrovascular accidents, stable angina, and acute coronary syndrome was n = 16, 10, 16, and 24, respectively. Risk factors such as being male, diagnosed hypertension, diabetes mellitus, and hyperlipidemia were not associated with events. Plasma fatty acids and oxylipins were analyzed with gas chromatography and HPLC-MS/MS, respectively. None of 24 fatty acids quantified were associated with events. In contrast, 39 plasma oxylipins were quantified, and 8 were significantly associated with events. These 8 oxylipins are known regulators of vascular tone. For example, every 1 unit increase in Thromboxane B 2 /Prostaglandin F 1 α and every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid, thromboxane B2, or 11,12-dihydroxyeicosatrienoic acid (DiHETrE) increased the odds of having had ≥2 events versus no event (p < 0.05). The greatest predictor was plasma 8,9-DiHETrE, which increased the odds of acute coronary syndrome by 92-fold. In conclusion, specific oxylipins were highly associated with clinical events and may represent specific biomarkers and (or) therapeutic targets of cardiovascular disease.

  3. Transcultural adaptation and validation of the Celiac Disease Quality of Life (CD-QOL survey, a specific questionnaire to measure quality of life in patients with celiac disease

    Directory of Open Access Journals (Sweden)

    Francesc Casellas

    2013-12-01

    Full Text Available Introduction: celiac disease is a chronic condition that requires continued treatment, with the resultant impact on health-related quality of life (HRQOL of people who suffer it. Most studies in this field have used generic questionnaires to measure HRQOL in celiac patients. It was therefore decided to conduct a study to translate into Spanish and validate a specific questionnaire for celiac disease, the Celiac Disease Quality Of Life Survey (CD-QOL. Objectives: to translate and validate in Spanish the specific celiac disease questionnaire CD-QOL. Methods: a multicenter, prospective, observational study was designed consisting of two phases: In the first phase, the questionnaire was translated and adapted into Spanish using the translation/back translation procedure and an understandability study. In the second phase, internal consistency of the translated questionnaire was analyzed. For this, results of the CD-QOL were compared to those of EuroQol and the Daily Fatigue Impact Scale (D-FIS. Understandability of the translated and adapted questionnaire was tested in six patients, and the validation study was done in 298 celiac patients (201 treated with a gluten-free diet and 97 at diagnosis. Results: in both celiac groups, Cronbach's alpha coefficient was high (0.90, feasibility was excellent (99.2 % of patients completed all questions, and there were no ceiling and floor effects. Spearman correlation to EuroQol and D-FIS was statistically significant (p < 0.05. CD-QOL score was different depending on whether state of health was good, fair, or poor based on the EuroQol score. Conclusion: the Spanish version of the CD-QOL is a valid tool for measuring HRQOL in celiac patients.

  4. Diagnostic sensitivity and specificity of a participatory disease surveillance method for highly pathogenic avian influenza in household chicken flocks in Indonesia.

    Science.gov (United States)

    Robyn, M; Priyono, W B; Kim, L M; Brum, E

    2012-06-01

    A study was conducted to assess the diagnostic sensitivity and specificity of a disease surveillance method for diagnosis of highly pathogenic avian influenza (HPAI) outbreaks in household chicken flocks used by participatory disease surveillance (PDS) teams in Yogyakarta Province, Indonesia. The Government of Indonesia, in partnership with the Food and Agriculture Organization of the United Nations, has implemented a PDS method for the detection of HPAI outbreaks in poultry since 2006. The PDS method in Indonesia utilizes both a clinical case definition (CD) and the result of a commercial rapid antigen test kit Yogyakarta 55611, to diagnose HPAI outbreaks, primarily in backyard chicken flocks. The following diagnostic sensitivities and specificities were obtained relative to real-time reverse transcription-PCR as the gold standard diagnostic test: 1) 89% sensitivity (CI95: 75%-97%) and 96% specificity (CI95: 89%-99%) for the PDS CD alone; 2) 86% sensitivity (CI95: 71%-95%) and 99% specificity (CI95: 94%-100%) for the rapid antigen test alone; and 3) 84% sensitivity (CI95: 68%-94%) and 100% specificity (CI95: 96%-100%) for the PDS CD result combined with the rapid antigen test result. Based on these results, HPAI outbreaks in extensively raised household chickens can be diagnosed with sufficient sensitivity and specificity using the PDS method as implemented in Indonesia. Subject to further field evaluation, data from this study suggest that the diagnostic sensitivity of the PDS method may be improved by expanding the PDS CD to include more possible clinical presentations of HPAI and by increasing the number of rapid antigen tests to three different birds with HPAI-compatible signs of same flock.

  5. Night shift work at specific age ranges and chronic disease risk factors.

    Science.gov (United States)

    Ramin, Cody; Devore, Elizabeth E; Wang, Weike; Pierre-Paul, Jeffrey; Wegrzyn, Lani R; Schernhammer, Eva S

    2015-02-01

    We examined the association of night shift work history and age when night shift work was performed with cancer and cardiovascular disease risk factors among 54 724 women in the Nurses' Health Study (NHS) II. We calculated age-adjusted and socioeconomic status-adjusted means and percentages for cancer and cardiovascular risk factors in 2009 across categories of night shift work history. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for key risk factors among 54 724 participants (72% ever shift workers). We further examined these associations by age (20-25, 26-35, 36-45 and 46+ years) at which shift work was performed. Ever night shift workers had increased odds of obesity (body mass index ≥30 kg/m(2); OR=1.37, 95% CI 1.31 to 1.43); higher caffeine intake (≥131 mg/day; OR=1.16, 95% CI 1.12 to 1.22) and total calorie intake (≥1715 kcal/day; OR=1.09, 95% CI 1.04 to 1.13); current smoking (OR=1.30, 95% CI 1.19 to 1.42); and shorter sleep durations (≤7 h of sleep/day; OR=1.19, 95% CI 1.15 to 1.24) compared to never night shift workers. These estimates varied depending on age at which night work was performed, with a suggestion that night shift work before age 25 was associated with fewer risk factors compared to night shift work at older ages. Our results indicate that night shift work may contribute to an adverse chronic disease risk profile, and that risk factors may vary depending on the age at which night shift work was performed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. IT-based Psychosocial Distress Screening in Patients with Sarcoma and Parental Caregivers via Disease-specific Online Social Media Communities.

    Science.gov (United States)

    Pohlig, Florian; Lenze, Ulrich; Muhlhofer, Heinrich M L; Lenze, Florian W; Schauwecker, Johannes; Knebel, Carolin; Zimmermann, Tanja; Herschbach, Peter

    2017-01-01

    Psychosocial distress can be frequently observed in patients with sarcoma, depicting a relevant clinical problem. However, prospective data collection on psychosocial distress in patients with rare tumors is often time-consuming. In this context, social media such as Facebook can serve as a potential platform to expand research. The aim of this study was to assess the feasibility of psychosocial distress screening in patients with osteosarcoma and Ewing's sarcoma via social media. For this study an online questionnaire including general information and self-assessment distress measurement tools for patients and parents was created. The link to the questionnaire was then posted on the main page of the two largest disease-specific Facebook communities on osteosarcoma and Ewing's sarcoma. Within 2 months, 28 patients and 58 parents of patients were enrolled. All patients with osteosarcoma and Ewing's sarcoma, as well as the majority of parental caregivers of such patients, showed relevant psychosocial distress levels. Crowdsourcing via disease-specific patient communities on Facebook is feasible and provides great potential for acquisition of medical data of rare diseases. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Amyloid-β peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease.

    Science.gov (United States)

    Hanenberg, Michael; McAfoose, Jordan; Kulic, Luka; Welt, Tobias; Wirth, Fabian; Parizek, Petra; Strobel, Lisa; Cattepoel, Susann; Späni, Claudia; Derungs, Rebecca; Maier, Marcel; Plückthun, Andreas; Nitsch, Roger M

    2014-09-26

    Passive immunization with anti-amyloid-β peptide (Aβ) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aβ-specific DARPins. We further showed their ability to delay Aβ aggregation and prevent Aβ-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aβ-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aβ levels. These findings demonstrate the therapeutic potential of Aβ-specific DARPins for the treatment of Alzheimer disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Conservation of species, volume, and belief in patients with Alzheimer's disease: the issue of domain specificity and conceptual impairment.

    Science.gov (United States)

    Zaitchik, Deborah; Solomon, Gregg E A

    2009-09-01

    Two studies investigated whether patients with Alzheimer's disease (AD) suffer high-level and category-specific impairment in the conceptual domain of living things. In Experiment 1, AD patients and healthy young and healthy elderly controls took part in three tasks: the conservation of species, volume, and belief. All 3 tasks required tracking an object's identity in the face of irrelevant but salient transformations. Healthy young and elderly controls performed at or near ceiling on all tasks. AD patients were at or near ceiling on the volume and belief tasks, but only about half succeeded on the species task. Experiment 2 demonstrated that the results were not due to simple task demands. AD patients' failure to conserve species indicates that they are impaired in their theoretical understanding of living things, and their success on the volume and belief tasks suggests that the impairment is domain-specific. Two hypotheses are put forward to explain the phenomenon: The first, a category-specific account, holds that the intuitive theory of biology undergoes pervasive degradation; the second, a hybrid domain-general/domain-specific account, holds that impairment to domain-general processes such as executive function interacts with core cognition, the primitive elements that are the foundation of domain-specific knowledge.

  9. Maternal Germline-Specific Genes in the Asian Malaria Mosquito Anopheles stephensi: Characterization and Application for Disease Control

    Science.gov (United States)

    Biedler, James K.; Qi, Yumin; Pledger, David; Macias, Vanessa M.; James, Anthony A.; Tu, Zhijian

    2014-01-01

    Anopheles stephensi is a principal vector of urban malaria on the Indian subcontinent and an emerging model for molecular and genetic studies of mosquito biology. To enhance our understanding of female mosquito reproduction, and to develop new tools for basic research and for genetic strategies to control mosquito-borne infectious diseases, we identified 79 genes that displayed previtellogenic germline-specific expression based on RNA-Seq data generated from 11 life stage–specific and sex-specific samples. Analysis of this gene set provided insights into the biology and evolution of female reproduction. Promoters from two of these candidates, vitellogenin receptor and nanos, were used in independent transgenic cassettes for the expression of artificial microRNAs against suspected mosquito maternal-effect genes, discontinuous actin hexagon and myd88. We show these promoters have early germline-specific expression and demonstrate 73% and 42% knockdown of myd88 and discontinuous actin hexagon mRNA in ovaries 48 hr after blood meal, respectively. Additionally, we demonstrate maternal-specific delivery of mRNA and protein to progeny embryos. We discuss the application of this system of maternal delivery of mRNA/miRNA/protein in research on mosquito reproduction and embryonic development, and for the development of a gene drive system based on maternal-effect dominant embryonic arrest. PMID:25480960

  10. [Prostate specific antigen--PSA and histopathological findings of endometrium in women with fibrocystic breast disease].

    Science.gov (United States)

    Radowicki, Stanisław; Kunicki, Michał

    2010-02-01

    The aim of the study was to evaluate the relationship between serum free and total PSA and histopathological findings in women with fibrocystic mastopathy. 176 women with fibrocystic breast disease, aged 18 to 45 years.--Group I: comprised 114 patients with cysts 10 mm in diameter. The control group consisted of 46 healthy women aged 18 - 45 years who had no breast pathology Total PSA (PSA-T) and free PSA (PSA-Free) were measured by an ultra-sensitive fluoroimmunometric DELFIA assay (Prostatus PSA Free/Total Wallac, Turku, Finland). The detection limit for PSA was 0.01 ng/ml. Endometrial samples have been obtained with Pipelle probe between 22 and 24 days of the menstrual cycle. In the control group secretory endometrium was more frequently detected than in the mastopathy group (chi2 = 11,15, p = 0.01). Proliferatory (chi2 = 8.27, p = 0.004) and presecretory endometrium (chi2 = 4.61, p = 0.03) were more frequently detected in the mastopathy group than in controls. We did not find statistically significant relationship between the mean PSA concentrations between the groups in relation to histopathological findings. No relationships between free and total PSA measured in the follicular phase of the menstrual cycle and endometrial findings were detected in our study. Further research is required to evaluate the relationship between PSA and endometrial findings.

  11. Do patients with rapid eye movement sleep behavior disorder have a disease-specific personality?

    Science.gov (United States)

    Sasai, Taeko; Inoue, Yuichi; Matsuura, Masato

    2012-06-01

    Rapid eye movement sleep behavior disorder (RBD) occurs idiopathically (iRBD), frequently representing a prodromal phase of Parkinson's disease (PD). Previous reports have described that patients with PD have premorbid personality profiles such as industriousness, inflexibility, cautiousness, and lack of novelty seeking. As well, psychological stress often aggravates RBD symptoms. These phenomena encouraged us to investigate personality profiles in iRBD patients. In this study, 53 patients with iRBD and 49 age and sex-matched healthy controls (HC) were enrolled. We used the revised version of the NEO Personality Inventory (NEO-PIR) to measure the personality of these subjects, and the 5 domains and the 30 facets of the NEO-PIR were compared between the two groups. Within the iRBD group, we investigated the association between RBD variables, e.g. the proportion of REM sleep without atonia (RWA/REM), length of RBD morbidity, frequency of vocalization or abnormal behavior, and the variables of NEO-PIR. In the patients, olfactory function was significantly lower than that of healthy controls, but the inventory differences were not significant. The inventory showed no association with any RBD variable, or the existence of aggravation of these symptoms triggered by psychological stress, or olfactory dysfunction. These results suggest that RBD patients do not have a personality profile that might predict PD development. The personality profile itself cannot explain the psychological-stress-dependent aggravation of RBD symptoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. A monoclonal antibody to inclusion body disease of cranes virus enabling specific immunohistochemistry and competitive ELISA

    Science.gov (United States)

    Letchworth, G.J.; Fishel, J.R.; Hansen, W.R.

    1997-01-01

    Inclusion body disease of cranes (IBDC) herpesvirus kills some infected cranes and persists in convalescent animals. To enable further study and rapid identification of carrier animals, we developed a monoclonal antibody (MAb) to IBDC virus and used it in immunohistochemistry and a competitive enzyme-linked immunosorbent assay (ELISA). We used conventional techniques to make murine MAbs directed against IBDC virus purified from infected duck embryo cells. Hybridomas reacting in an ELISA with IBDC virus but not uninfected duck embryo cells were characterized by radioimmunoprecipitation, in situ immunohistochemistry, and competitive ELISA with neutralizing and nonneutralizing crane sera. MAb 2C11 immunoprecipitated 59-, 61-, and 110-kD proteins from IBDC virus-infected but not uninfected cells and stained glutaraldehyde-fixed IBDC virus plaques but not surrounding uninfected duck embryo cells in vitro. Antibody 2C11 did not react with duck embryo cells infected with falcon herpesvirus, psittacine herpesvirus, infectious laryngotracheitis, pigeon herpesvirus, or duck plague virus. A competitive ELISA using antibody 2C11 identified most sera that were positive in the neutralization test. This antibody will be useful in further characterizing IBDC virus, its pathogenesis, and its natural history.

  13. Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases.

    Directory of Open Access Journals (Sweden)

    Matthew J Haney

    Full Text Available The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD. This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders.

  14. Specific egg yolk immunoglobulin as a new preventive approach for Shiga-toxin-mediated diseases.

    Directory of Open Access Journals (Sweden)

    Paola Neri

    Full Text Available Shiga toxins (Stxs are involved in the development of severe systemic complications associated with enterohemorrhagic Escherichia coli (EHEC infection. Various neutralizing agents against Stxs are under investigation for management of EHEC infection. In this study, we immunized chickens with formalin-inactivated Stx-1 or Stx-2, and obtained immunoglobulin Y (IgY from the egg yolk. Anti-Stx-1 IgY and anti-Stx-2 IgY recognized the corresponding Stx A subunit and polymeric but not monomeric B subunit. Anti-Stx-1 IgY and anti-Stx-2 IgY suppressed the cytotoxicity of Stx-1 and Stx-2 to HeLa 229 cells, without cross-suppressive activity. The suppressive activity of these IgY was abrogated by pre-incubation with the corresponding recombinant B subunit, which suggests that the antibodies directed to the polymeric B subunits were predominantly involved in the suppression. In vivo, the intraperitoneal or intravenous administration of these IgY rescued mice from death caused by intraperitoneal injection of the corresponding toxin at a lethal dose. Moreover, oral administration of anti-Stx-2 IgY reduced the mortality of mice infected intestinally with EHEC O157:H7. Our results therefore suggest that anti-Stx IgY antibodies may be considered as preventive agents for Stx-mediated diseases in EHEC infection.

  15. Serotype Specificity of Antibodies against Foot-and-Mouth Disease Virus in Cattle in Selected Districts in Uganda

    DEFF Research Database (Denmark)

    Mwiine, F.N.; Ayebazibwe, C.; Olaho-Mukani, W.

    2010-01-01

    Uganda had an unusually large number of foot-and-mouth disease (FMD) outbreaks in 2006, and all clinical reports were in cattle. A serological investigation was carried out to confirm circulating antibodies against foot-and-mouth disease virus (FMDV) by ELISA for antibodies against non-structural......Uganda had an unusually large number of foot-and-mouth disease (FMD) outbreaks in 2006, and all clinical reports were in cattle. A serological investigation was carried out to confirm circulating antibodies against foot-and-mouth disease virus (FMDV) by ELISA for antibodies against non......-structural proteins and structural proteins. Three hundred and forty-nine cattle sera were collected from seven districts in Uganda, and 65% of these were found positive for antibodies against the non-structural proteins of FMDV. A subset of these samples were analysed for serotype specificity of the identified...... antibodies. High prevalences of antibodies against non-structural proteins and structural proteins of FMDV serotype O were demonstrated in herds with typical visible clinical signs of FMD, while prevalences were low in herds without clinical signs of FMD. Antibody titres were higher against serotype O than...

  16. Protein-energy wasting syndrome in advanced chronic kidney disease: prevalence and specific clinical characteristics.

    Science.gov (United States)

    Pérez-Torres, Almudena; González Garcia, M Elena; San José-Valiente, Belén; Bajo Rubio, M Auxiliadora; Celadilla Diez, Olga; López-Sobaler, Ana M; Selgas, Rafael

    Protein-energy wasting (PEW) is associated with increased mortality and differs depending on the chronic kidney disease (CKD) stage and the dialysis technique. The prevalence in non-dialysis patients is understudied and ranges from 0 to 40.8%. To evaluate the nutritional status of a group of Spanish advanced CKD patients by PEW criteria and subjective global assessment (SGA). Cross-sectional study of 186 patients (101 men) with a mean age of 66.1±16 years. The nutritional assessment consisted of: SGA, PEW criteria, 3-day dietary records, anthropometric parameters and bioelectrical impedance vector analysis. The prevalence of PEW was 30.1%, with significant differences between men and women (22.8 vs. 33.8%, p intake. Women had higher levels of total cholesterol, HDL and a higher body fat percentage. The characteristics of patients with PEW were low albumin levels and a low total lymphocyte count, high proteinuria, low fat and muscle mass and a high Na/K ratio. The multivariate analysis found PEW to be associated with: proteinuria (OR: 1.257; 95% CI: 1.084-1.457, p=0.002), percentage of fat intake (OR: 0.903; 95% CI: 0.893-0.983, p=0.008), total lymphocyte count (OR: 0.999; 95% CI: 0.998-0.999, p=0.001) and cell mass index (OR: 0.995; 95% CI: 0.992-0.998). Malnutrition was identified in Spanish advanced CKD patients measured by different tools. We consider it appropriate to adapt new diagnostic elements to PEW criteria. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Genetic basis of cancer of the kidney: disease-specific approaches to therapy.

    Science.gov (United States)

    Linehan, W Marston; Vasselli, James; Srinivasan, Ramaprasad; Walther, McClellan M; Merino, Maria; Choyke, Peter; Vocke, Cathy; Schmidt, Laura; Isaacs, Jennifer S; Glenn, Gladys; Toro, Jorge; Zbar, Berton; Bottaro, Donald; Neckers, Len

    2004-09-15

    Studies during the past two decades have shown that kidney cancer is not a single disease; it is made up of a number of different types of cancer that occur in this organ. Clear cell renal carcinoma is characterized by mutation of the VHL gene. The VHL gene product forms a heterotrimeric complex with elongin C, elongin B, and Cul-2 to target hypoxia-inducible factors 1 and 2alpha for ubiquitin-mediated degradation. VHL-/- clear cell renal carcinoma overexpresses epidermal growth factor receptor and transforming growth factor alpha. Both hypoxia-inducible factor 1alpha and the epidermal growth factor receptor are potential therapeutic targets in clear cell renal carcinoma. Studies of the hereditary form of renal cell carcinoma (RCC) associated with hereditary papillary renal carcinoma (HPRC) determined that the c-Met proto-oncogene on chromosome 7 is the gene for HPRC and for a number of sporadic papillary RCCs. The HPRC c-Met mutations are activating mutations in the tyrosine kinase domain of the gene. The gene for a new form of hereditary RCC (Birt Hogg Dubé syndrome) associated with cutaneous tumors, lung cysts, and colon polyps or cancer has recently been identified. Studies are currently under way to determine what type of gene BHD is and how damage to this gene leads to kidney cancer. Individuals affected with hereditary leiomyomatosis renal cell carcinoma are at risk for the development of cutaneous leiomyomas, uterine leiomyomas (fibroids), and type 2 papillary RCC. The HLRC gene has been found to be the Krebs cycle enzyme, fumarate hydratase. Studies are under way to understand the downstream pathway of this cancer gene.

  18. Attribution of global foodborne disease to specific foods: Findings from a World Health Organization structured expert elicitation.

    Directory of Open Access Journals (Sweden)

    Sandra Hoffmann

    Full Text Available Recently the World Health Organization, Foodborne Disease Burden Epidemiology Reference Group (FERG estimated that 31 foodborne diseases (FBDs resulted in over 600 million illnesses and 420,000 deaths worldwide in 2010. Knowing the relative role importance of different foods as exposure routes for key hazards is critical to preventing illness. This study reports the findings of a structured expert elicitation providing globally comparable food source attribution estimates for 11 major FBDs in each of 14 world subregions.We used Cooke's Classical Model to elicit and aggregate judgments of 73 international experts. Judgments were elicited from each expert individually and aggregated using both equal and performance weights. Performance weighted results are reported as they increased the informativeness of estimates, while retaining accuracy. We report measures of central tendency and uncertainty bounds on food source attribution estimate. For some pathogens we see relatively consistent food source attribution estimates across subregions of the world; for others there is substantial regional variation. For example, for non-typhoidal salmonellosis, pork was of minor importance compared to eggs and poultry meat in the American and African subregions, whereas in the European and Western Pacific subregions the importance of these three food sources were quite similar. Our regional results broadly agree with estimates from earlier European and North American food source attribution research. As in prior food source attribution research, we find relatively wide uncertainty bounds around our median estimates.We present the first worldwide estimates of the proportion of specific foodborne diseases attributable to specific food exposure routes. While we find substantial uncertainty around central tendency estimates, we believe these estimates provide the best currently available basis on which to link FBDs and specific foods in many parts of the world

  19. Attribution of global foodborne disease to specific foods: Findings from a World Health Organization structured expert elicitation.

    Science.gov (United States)

    Hoffmann, Sandra; Devleesschauwer, Brecht; Aspinall, Willy; Cooke, Roger; Corrigan, Tim; Havelaar, Arie; Angulo, Frederick; Gibb, Herman; Kirk, Martyn; Lake, Robin; Speybroeck, Niko; Torgerson, Paul; Hald, Tine

    2017-01-01

    Recently the World Health Organization, Foodborne Disease Burden Epidemiology Reference Group (FERG) estimated that 31 foodborne diseases (FBDs) resulted in over 600 million illnesses and 420,000 deaths worldwide in 2010. Knowing the relative role importance of different foods as exposure routes for key hazards is critical to preventing illness. This study reports the findings of a structured expert elicitation providing globally comparable food source attribution estimates for 11 major FBDs in each of 14 world subregions. We used Cooke's Classical Model to elicit and aggregate judgments of 73 international experts. Judgments were elicited from each expert individually and aggregated using both equal and performance weights. Performance weighted results are reported as they increased the informativeness of estimates, while retaining accuracy. We report measures of central tendency and uncertainty bounds on food source attribution estimate. For some pathogens we see relatively consistent food source attribution estimates across subregions of the world; for others there is substantial regional variation. For example, for non-typhoidal salmonellosis, pork was of minor importance compared to eggs and poultry meat in the American and African subregions, whereas in the European and Western Pacific subregions the importance of these three food sources were quite similar. Our regional results broadly agree with estimates from earlier European and North American food source attribution research. As in prior food source attribution research, we find relatively wide uncertainty bounds around our median estimates. We present the first worldwide estimates of the proportion of specific foodborne diseases attributable to specific food exposure routes. While we find substantial uncertainty around central tendency estimates, we believe these estimates provide the best currently available basis on which to link FBDs and specific foods in many parts of the world, providing guidance

  20. [Prostate specific antigen and NF-kB in prostatic disease: relation with malignancy].

    Science.gov (United States)

    Cansino, J R; Vera, R; Rodríguez de Bethencourt, F; Bouraoui, Y; Rodríguez, G; Prieto, A; de la Peña, J; Paniagua, R; Royuela, M

    2011-01-01

    NF-kB (p50/p65) is a transcription factor involved in TNF-α-induced cell death resistance by promoting several antiapoptotic genes. We intend to relate the expression of NF-kB (p50 and p65) with serum levels of prostate-specific antigen (PSA), both in normal males and in those with pathologic conditions of the prostate. this study was carried out in 5 normal, 24 benign prostatic hyperplastic (BPH) and 19 patients with prostate cancer (PC). Immunohistochemical and Western blot analyses were performed on tissue and serum PSA was assayed by PSA DPC Immulite assays (Diagnostics Products Corporation, Los Angeles, CA). in controls, p65 NF-kB was not found and p50 was scantly detected in 60% normal samples in the cytoplasm of epithelial cells. Both p50 and p65 were expressed in 62.5% of the samples with BPH and in 63.2% of those with PC. Both increased its frequency of expression with higher PSA serum levels. Activation of NF-kB revealed by its nuclear translocation in prostate cancer could be related to cancer progression and elevated seric PSA levels. A better understanding of the biologic mechanism by which circulating PSA levels increase and its relation with NF-kB expression is needed. Possibly, NF-kB blockage could be used as a therapeutic target to counteract proliferation in prostate cancer. Copyright © 2010 AEU. Published by Elsevier Espana. All rights reserved.

  1. Intracranial Vascular Disease Evaluation With Combined Vessel Wall Imaging And Patient Specific Hemodynamics

    Science.gov (United States)

    Samson, Kurt; Mossa-Basha, Mahmud; Yuan, Chun; Canton, Maria De Gador; Aliseda, Alberto

    2017-11-01

    Intracranial vascular pathologies are evaluated with angiography, conventional digital subtraction angiography or non-invasive (MRI, CT). Current techniques present limitations on the resolution with which the vessel wall characteristics can be measured, presenting a major challenge to differential diagnostic of cerebral vasculopathies. A new combined approach is presented that incorporates patient-specific image-based CFD models with intracranial vessel-wall MRI (VWMRI). Comparisons of the VWMRI measurements, evaluated for the presence of wall enhancement and thin-walled regions, against CFD metrics such as wall shear stress (WSS), and oscillatory shear index (OSI) are used to understand how the new imaging technique developed can predict the influence of hemodynamics on the deterioration of the aneurysmal wall, leading to rupture. Additionally, histology of each resected aneurysm, evaluated for inflammatory infiltration and wall thickness features, is used to validate the analysis from VWMRI and CFD. This data presents a solid foundation on which to build a new framework for combined VWMRI-CFD to predict unstable wall changes in unruptured intracranial aneurysms, and support clinical monitoring and intervention decisions.

  2. Insights for the assessment of the economic impact of endemic diseases: specific adaptation of economic frameworks using the case of bovine viral diarrhoea.

    Science.gov (United States)

    Stott, A W; Gunn, G J

    2017-04-01

    Generic frameworks for the economic analysis of farm animal disease are now well established. The paper, therefore, uses bovine viral diarrhoea (BVD) as an example to explore how these frameworks need to be adapted to fit the characteristics of a particular disease and the specific objectives of the analysis. In the case of BVD, given the relative strength of tests available to correctly identify virus-positive animals, thus enabling them to be culled, the emphasis has been on cost-benefit analysis of regional and national certification/eradication schemes. Such analyses in turn raise interesting questions about farmer uptake and maintenance of certification schemes and the equity and cost-effective implementation of these schemes. The complex epidemiology of BVD virus infections and the long-term, widespread and often occult nature of BVD effects make economic analysis of the disease and its control particularly challenging. However, this has resulted in a wider whole-farm perspective that captures the influence of multiple decisions, not just those directly associated with disease prevention and control. There is a need to include management of reproduction, risk and enterprise mix in the research on farmer decision-making, as all these factors impinge on, and are affected by, the spread of BVD.

  3. Sex differences in disease-specific health status measures in patients with symptomatic peripheral artery disease: Data from the PORTRAIT study.

    Science.gov (United States)

    Roumia, Mazen; Aronow, Herbert D; Soukas, Peter; Gosch, Kensey; Smolderen, Kim G; Spertus, John A; Abbott, J Dawn

    2017-04-01

    Peripheral artery disease (PAD) is associated with poor health status (symptoms, functioning, quality of life (QOL)). Whether sex differences exist in PAD-specific health status is unknown. In patients presenting to a specialty clinic with new-onset or recent exacerbation of PAD, we examined sex differences as assessed by the Peripheral Artery Questionnaire (PAQ). The Patient-centered Outcomes Related to TReatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study is a multicenter, international prospective study of patients with new or worsening PAD symptoms. Baseline characteristics and mean PAQ scores were compared among women ( n=481) and men ( n=793) before they underwent treatment. The independent association of sex with health status was assessed with multivariable linear regression. As compared with men, women were less often Caucasian, married and employed, and more often lacking health insurance, living alone (36.2% vs 23.6%, pPAQ scores on all domains (physical functioning adjusted mean difference of -8.40, p<0.001; social functioning adjusted mean difference of -6.8, p<0.001; QOL adjusted mean difference of -6.7, p<0.001), although no differences were observed in treatment satisfaction (adjusted mean difference -0.20, p=0.904). Despite similar ABIs, women presenting with symptoms of PAD had poorer PAD-specific functioning as compared with men, impacting all major health status domains, independent of socio-economic and clinical characteristics.

  4. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease.

    Science.gov (United States)

    Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R; Challa, Pavan Kumar; Cohen, Samuel I A; Linse, Sara; Dobson, Christopher M; Knowles, Tuomas P J; Vendruscolo, Michele

    2017-01-10

    The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.

  5. Protein-energy wasting syndrome in advanced chronic kidney disease: Prevalence and specific clinical characteristics

    Directory of Open Access Journals (Sweden)

    Almudena Pérez-Torres

    2018-03-01

    Full Text Available Introduction: Protein-energy wasting (PEW is associated with increased mortality and differs depending on the chronic kidney disease (CKD stage and the dialysis technique. The prevalence in non-dialysis patients is understudied and ranges from 0 to 40.8%. Objective: To evaluate the nutritional status of a group of Spanish advanced CKD patients by PEW criteria and subjective global assessment (SGA. Patients and methods: Cross-sectional study of 186 patients (101 men with a mean age of 66.1 ± 16 years. The nutritional assessment consisted of: SGA, PEW criteria, 3-day dietary records, anthropometric parameters and bioelectrical impedance vector analysis. Results: The prevalence of PEW was 30.1%, with significant differences between men and women (22.8 vs. 33.8%, p < 0.005, while 27.9% of SGA values were within the range of malnutrition. No differences were found between the 2 methods. Men had higher proteinuria, percentage of muscle mass and nutrient intake. Women had higher levels of total cholesterol, HDL and a higher body fat percentage. The characteristics of patients with PEW were low albumin levels and a low total lymphocyte count, high proteinuria, low fat and muscle mass and a high Na/K ratio.The multivariate analysis found PEW to be associated with: proteinuria (OR: 1.257; 95% CI: 1.084–1.457, p = 0.002, percentage of fat intake (OR: 0.903; 95% CI: 0.893–0.983, p = 0.008, total lymphocyte count (OR: 0.999; 95% CI: 0.998–0.999, p = 0.001 and cell mass index (OR: 0.995; 95% CI: 0.992–0.998. Conclusion: Malnutrition was identified in Spanish advanced CKD patients measured by different tools. We consider it appropriate to adapt new diagnostic elements to PEW criteria. Resumen: Introducción: El desgaste proteico energético (DPE se asocia a mayor mortalidad y difiere dependiendo del estadio de la enfermedad renal y de la técnica de diálisis. Su prevalencia en pacientes sin di

  6. Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

    Science.gov (United States)

    Akhtar, Rizwan S; Xie, Sharon X; Chen, Yin J; Rick, Jacqueline; Gross, Rachel G; Nasrallah, Ilya M; Van Deerlin, Vivianna M; Trojanowski, John Q; Chen-Plotkin, Alice S; Hurtig, Howard I; Siderowf, Andrew D; Dubroff, Jacob G; Weintraub, Daniel

    2017-01-01

    Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

  7. Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

    Directory of Open Access Journals (Sweden)

    Rizwan S Akhtar

    Full Text Available Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2% were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%. Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

  8. Acquired immune deficiency syndrome: specific aspects of the disease in Haiti.

    Science.gov (United States)

    Guerin, J M; Malebranche, R; Elie, R; Laroche, A C; Pierre, G D; Arnoux, E; Spira, T J; Dupuy, J M; Seemayer, T A; Pean-Guichard, C

    1984-01-01

    This paper presents clinical data on 41 patients (29 male and 12 female) from Haiti who presented with acquired immunedeficiency syndrome (AIDS). Their mean age was 32 years (range 17-61 years). 4 of thes cases were homosexual or bisexual; none was an illicit drug user or a hemophiliac. In addition, 3 of the female patients had sexual contact with a male partner with AIDS. 4 patients had received blood transfusions before their illness. The most prominent clinical symptom in this series was chronic diarrhea of 2-33 months' duration, which occurrred in 39 patients (95%). Also reporte were marked weight loss (95%), fatigue (95%), prolonger fever (90%), and nodular or maculopapular skin lesions (54%). Opportunistic infections in this series included oroesophageal candidiasis (88%) and intestinal cryptosporidiosis (31%). Tuberculosis developed in 22% of patients. Immunologic evaluation revealed profoundly depressed T-helper cells and an inverted T-helper/T-suppressor cell ratio. Biologic markers included elevated alpha-1 thymosin and beta-2 microglobulin levels, elevated immune complexes, and the presence of acid-labile interferon. Of interest were differences in the clinical expression of AIDS between this series and cases in the US. The Haitian data suggest a higher incidencs of female cases,a predominance of gastrointestinal symptoms rather than respiratory symptoms and lymphadenopathy, a frequent association with tuberculosis, and a relatively low incidence of Kaposi's sarcoma or P. carinii pneumonia compared to the situation in the US. As in the US, where most AIDS cases are concentrated in New York and California, most AIDS cases in Haiti are found in residents of Port-au-Prince and Carrefour, which are centers for male and female prostitution.

  9. 125I-Clq-binding and specific antibodies as indicators of pulmonary disease activity in cystic fibrosis

    International Nuclear Information System (INIS)

    Moss, R.B.; Hsu, Y.P.; Lewiston, N.J.

    1981-01-01

    We studied the incidence and levels of circulating immune complexes by the 125 I-Clq-binding assay in patients with cystic fibrosis in relation to clinical respiratory status and specific IgG and IgE antibodies to Pseudomonas aeruginosa. Staphylococcus aureus, Aspergillus fumigatus, and Candida albicans. Overall prevalence of CIC was 43%, but 86% of serially studied patients had evidence of CIC at some time. Patients with acute respiratory exacerbations and deteriorating pulmonary function had a higher incidence of CIC (76%) as compared to stable patients (36%, P less than 0.01), as well as significantly higher levels of CIC. Acute exacerbations were also associated with significant increases in IgG antibody to Pseudomonas (P less than 0.005) but not in other antibodies. CIC did not correlate with Pseudomonas-specific IgG nor with any other specific antibody studied. A variety of age-related differences in specific antibody levels were seen. The episodic appearance of CIC is common in CF and is usually associated with exacerbation of lung disease

  10. Simultaneous measurements of auto-immune and infectious disease specific antibodies using a high throughput multiplexing tool.

    Directory of Open Access Journals (Sweden)

    Atul Asati

    Full Text Available Considering importance of ganglioside antibodies as biomarkers in various immune-mediated neuropathies and neurological disorders, we developed a high throughput multiplexing tool for the assessment of gangliosides-specific antibodies based on Biolpex/Luminex platform. In this report, we demonstrate that the ganglioside high throughput multiplexing tool is robust, highly specific and demonstrating ∼100-fold higher concentration sensitivity for IgG detection than ELISA. In addition to the ganglioside-coated array, the high throughput multiplexing tool contains beads coated with influenza hemagglutinins derived from H1N1 A/Brisbane/59/07 and H1N1 A/California/07/09 strains. Influenza beads provided an added advantage of simultaneous detection of ganglioside- and influenza-specific antibodies, a capacity important for the assay of both infectious antigen-specific and autoimmune antibodies following vaccination or disease. Taken together, these results support the potential adoption of the ganglioside high throughput multiplexing tool for measuring ganglioside antibodies in various neuropathic and neurological disorders.

  11. Gout disease-specific quality of life and the association with gout characteristics

    Directory of Open Access Journals (Sweden)

    Jan D Hirsch

    2010-03-01

    Full Text Available Jan D Hirsch1,4, Robert Terkeltaub4, Dinesh Khanna5, Jasvinder Singh6, Andrew Sarkin2, Micki Shieh2, Arthur Kavanaugh3, Susan J Lee3,41Skaggs School of Pharmacy and Pharmaceutical Sciences, 2Health Services Research, 3Center for Innovative  Therapy, Division of Rheumatology, Allergy, and Immunology, University of California San Diego, La Jolla, CA, USA; 4Veterans Administration San Diego Healthcare System, La Jolla, CA, USA; 5Department of Medicine/Rheumatology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 6Department of Medicine/Rheumatology, Minneapolis VA Healthcare System, Minneapolis MN, USAPurpose: Assess the association of gout characteristics with health-related quality of life (HRQoL using a new gout-specific HRQoL instrument, the Gout Impact Scale (GIS.Patients and methods: Gout patients completed the GIS (five scales [0–100 score each] representing impact of gout overall [three scales] and during an attack [two scales] and other questions describing recent gout attacks, treatment, gout history, comorbidities, and demographics. Physicians confirmed gout diagnosis, presence of tophi, and most recent serum uric acid (sUA level. Relationships between gout characteristics and GIS scores were examined using analysis of variance and correlation analyses.Results: The majority of patients were male (90.2% with a mean age of 62.2 (±11.8 years. Approximately one-half (49.7% reported ≥3 gout attacks in the past year and the majority (57.9% reported experiencing gout-related pain between attacks. Patients had appreciable concern about their gout (“gout concern overall” scale, 63.1 ± 28.0 but believed their treatment was adequate (“unmet gout treatment need” scale (38.2 ± 21.4 below scale mid-point. Significantly worse GIS scores were associated with increasing attack frequency and greater amount of time with pain between attacks (most scales, P < 0.001. Common objective measures such

  12. Long-term follow-up of cardiac function in patients with Hodgkin's disease treated with mediastinal irradiation and combination chemotherapy including doxorubicin

    International Nuclear Information System (INIS)

    LaMonte, C.S.; Yeh, S.D.; Straus, D.J.

    1986-01-01

    Among 41 evaluable patients whose first treatment for advanced Hodgkin's disease had consisted of alternating cycles of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in addition to low-dose mediastinal irradiation, 19 underwent retrospective cardiac evaluation by routine posteroanterior and lateral chest x-ray, 12-lead ECG, M-mode echocardiogram, and ECG-gated left ventricular blood pool scan at rest and during exercise. Fifteen patients had unequivocally normal left ventricular function by all these parameters. Two patients had minimally reduced left ventricular ejection fraction (LVEF) at rest with a normal increment with exercise. In two other patients with high normal resting LVEF and subnormal increment with exercise, the elevated resting values implied initial measurement in a nonbasal state. A twentieth patient (the oldest; one of two with active Hodgkin's disease at the time of evaluation and the stimulus for this study) had markedly reduced LVEF as determined by radionuclide cardiac angiography and had developed clinical congestive heart failure shortly before evaluation. Despite this patient, the study indicates that treatment with MOPP/ABVD and low-dose mediastinal irradiation entails low risk for cardiac complications

  13. The effects of infographics and several quantitative versus qualitative formats for cardiovascular disease risk, including heart age, on people's risk understanding.

    Science.gov (United States)

    Damman, Olga C; Vonk, Suzanne I; van den Haak, Maaike J; van Hooijdonk, Charlotte M J; Timmermans, Danielle R M

    2018-03-11

    To study how comprehension of cardiovascular disease (CVD) risk is influenced by: (1) infographics about qualitative risk information, with/without risk numbers; (2) which qualitative risk dimension is emphasized; (3) heart age vs. traditional risk format. For aim 1, a 2 (infographics versus text) x 2 (risk number versus no risk number) between-subjects design was used. For aim 2, three pieces of information were tested within-subjects. Aim 3 used a simple comparison group. Participants (45-65 yrs old) were recruited through an online access panel; low educated people were oversampled. They received hypothetical risk information (20%/61yrs). Primary outcomes: recall, risk appraisals, subjective/objective risk comprehension. behavioral intentions, information evaluations. Infographics of qualitative risk dimensions negatively affected recall, subjective risk comprehension and information evaluations. No effect of type of risk dimension was found on risk perception. Heart age influenced recall, comprehension, evaluations and affective risk appraisals. Infographics of hypothetical CVD risk information had detrimental effects on measures related to ris