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Sample records for comprehensive disease specific

  1. 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

  2. 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.

  3. 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.

  4. How specific are specific comprehension difficulties?

    DEFF Research Database (Denmark)

    Rønberg, Louise Flensted-Jensen; Petersen, Dorthe Klint

    2016-01-01

    as measured on a phonological coding measure. However, the proportion was smaller than the often reported 10-15 % and even smaller when average sight word recognition was also set as a criterion for word reading ability. Compared to average comprehenders, the poor comprehenders’ sight word recognition......This study explores the occurrence of poor comprehenders, i.e., children identified with reading comprehension difficulties in spite of age-appropriate word reading skills. It supports the findings that some children do show poor reading comprehension in spite of age-appropriate word reading...... and daily reading of literary texts were significantly below that of average readers. This study indicates that a lack of reading experience and, likewise, a lack of fluent word reading may be important factors in understanding nine-year-old poor comprehenders’ difficulties....

  5. Reading comprehension in Parkinson's disease.

    Science.gov (United States)

    Murray, Laura L; Rutledge, Stefanie

    2014-05-01

    Although individuals with Parkinson's disease (PD) self-report reading problems and experience difficulties in cognitive-linguistic functions that support discourse-level reading, prior research has primarily focused on sentence-level processing and auditory comprehension. Accordingly, the authors investigated the presence and nature of reading comprehension in PD, hypothesizing that (a) individuals with PD would display impaired accuracy and/or speed on reading comprehension tests and (b) reading performances would be correlated with cognitive test results. Eleven adults with PD and 9 age- and education-matched control participants completed tests that evaluated reading comprehension; general language and cognitive abilities; and aspects of attention, memory, and executive functioning. The PD group obtained significantly lower scores on several, but not all, reading comprehension, language, and cognitive measures. Memory, language, and disease severity were significantly correlated with reading comprehension for the PD group. Individuals in the early stages of PD without dementia or broad cognitive deficits can display reading comprehension difficulties, particularly for high- versus basic-level reading tasks. These reading difficulties are most closely related to memory, high-level language, and PD symptom severity status. The findings warrant additional research to delineate further the types and nature of reading comprehension impairments experienced by individuals with PD.

  6. Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

    Science.gov (United States)

    Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

    2017-07-01

    Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

  7. Comprehension in grammatical sentences at the level of specificity and schematicity in Alzheimer’s disease: an analysis psycholinguistics and cognitive

    Directory of Open Access Journals (Sweden)

    Berla Moreira de Moraes

    2016-10-01

    Full Text Available The present research aimed at identifying if there is any compromisse regarding the comprehension in grammatical sentences at the level of specificity, through the self-paced reading technique, produced by people suffering from Alzheimer. With the objective of reaching our goals and finding answers to our hypotheses, one experiment was carried out to analyse: the time of reaction while reading the sentence, the time of reaction for reading the comprehension questions and choosing the best answer, and the score of right answers given by Young adults (YA and healthy old (HO taken as groups of control and the old with likely Alzheimer (OLA as case group, considering sentences: at the level of schematicity and specificity. 10 YA, 10 HO and 10 OLA took part in the experiments, totalling thirty participants. Results show that, when compared to the old without cognitive decline, people suffering from Alzheimer presente inferior performance in comprehending conventional imagery when it comes to the rate of right answers and the time of response. As the result of the experiment, in relation to the level of specificity, people with Alzheimer need more time to read and give answers before schematic sentences, in which is also noticed the highest rate of wrong anwers. The hypothesis that the comprehension of conventional imagery in gramatical sentences at the level of specificity, is affected since the early stages of the Alzheimer disease was confirmed. We believe that this is influenced by the progressive cognitive decline of the working memory, by the speed of processing, by the decision making and also by the spacial and temporal orientation.

  8. Hand Specific Representations in Language Comprehension

    Directory of Open Access Journals (Sweden)

    Claire eMoody-Triantis

    2014-06-01

    Full Text Available Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand is recruited in language comprehension and action execution. An fMRI study tested right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences - a dominant hand effect -. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  9. Hand specific representations in language comprehension.

    Science.gov (United States)

    Moody-Triantis, Claire; Humphreys, Gina F; Gennari, Silvia P

    2014-01-01

    Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand) is recruited in language comprehension and action execution. An fMRI study tested self-reported right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences-a dominant hand effect. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a) language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b) language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  10. The challenges of reshaping disease specific and care oriented community based services towards comprehensive goals: a situation appraisal in the Western Cape Province, South Africa.

    Science.gov (United States)

    Schneider, Helen; Schaay, Nikki; Dudley, Lilian; Goliath, Charlyn; Qukula, Tobeka

    2015-09-30

    Similar to other countries in the region, South Africa is currently reorienting a loosely structured and highly diverse community care system that evolved around HIV and TB, into a formalized, comprehensive and integrated primary health care outreach programme, based on community health workers (CHWs). While the difficulties of establishing national CHW programmes are well described, the reshaping of disease specific and care oriented community services, based outside the formal health system, poses particular challenges. This paper is an in-depth case study of the challenges of implementing reforms to community based services (CBS) in one province of South Africa. A multi-method situation appraisal of CBS in the Western Cape Province was conducted over eight months in close collaboration with provincial stakeholders. The appraisal mapped the roles and service delivery, human resource, financing and governance arrangements of an extensive non-governmental organisation (NGO) contracted and CHW based service delivery infrastructure that emerged over 15-20 years in this province. It also gathered the perspectives of a wide range of actors - including communities, users, NGOs, PHC providers and managers - on the current state and future visions of CBS. While there was wide support for new approaches to CBS, there are a number of challenges to achieving this. Although largely government funded, the community based delivery platform remains marginal to the formal public primary health care (PHC) and district health systems. CHW roles evolved from a system of home based care and are limited in scope. There is a high turnover of cadres, and support systems (supervision, monitoring, financing, training), coordination between CHWs, NGOs and PHC facilities, and sub-district capacity for planning and management of CBS are all poorly developed. Reorienting community based services that have their origins in care responses to HIV and TB presents an inter-related set of resource

  11. Proverb and idiom comprehension in Alzheimer disease.

    Science.gov (United States)

    Kempler, D; Van Lancker, D; Read, S

    1988-01-01

    Twenty-nine patients diagnosed with Probable Alzheimer Disease were administered tests of word, familiar phrases (idioms and proverbs), and novel phrase comprehension. From the early stage of the disease, patients performed worse at understanding familiar phrases than single words or novel phrases. The results uphold common observations that AD patients have difficulty interpreting abstract meanings. Cognitive variables responsible for poor idiom/proverb comprehension and the clinical implications of this new protocol are discussed.

  12. 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.

  13. Investigating Patterns of Errors for Specific Comprehension and Fluency Difficulties

    Science.gov (United States)

    Koriakin, Taylor A.; Kaufman, Alan S.

    2017-01-01

    Although word reading has traditionally been viewed as a foundational skill for development of reading fluency and comprehension, some children demonstrate "specific" reading comprehension problems, in the context of intact word reading. The purpose of this study was to identify specific patterns of errors associated with reading…

  14. Use of Bloom's Taxonomy in Developing Reading Comprehension Specifications

    Science.gov (United States)

    Luebke, Stephen; Lorie, James

    2013-01-01

    This article is a brief account of the use of Bloom's Taxonomy of Educational Objectives (Bloom, Engelhart, Furst, Hill, & Krathwohl, 1956) by staff of the Law School Admission Council in the 1990 development of redesigned specifications for the Reading Comprehension section of the Law School Admission Test. Summary item statistics for the…

  15. A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies.

    Science.gov (United States)

    McAllister, Brian P; Williams, Emmanuelle; Clarke, Kofi

    2018-06-02

    Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and "at risk" populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease

  16. Comprehension of Spacecraft Telemetry Using Hierarchical Specifications of Behavior

    Science.gov (United States)

    Havelund, Klaus; Joshi, Rajeev

    2014-01-01

    A key challenge in operating remote spacecraft is that ground operators must rely on the limited visibility available through spacecraft telemetry in order to assess spacecraft health and operational status. We describe a tool for processing spacecraft telemetry that allows ground operators to impose structure on received telemetry in order to achieve a better comprehension of system state. A key element of our approach is the design of a domain-specific language that allows operators to express models of expected system behavior using partial specifications. The language allows behavior specifications with data fields, similar to other recent runtime verification systems. What is notable about our approach is the ability to develop hierarchical specifications of behavior. The language is implemented as an internal DSL in the Scala programming language that synthesizes rules from patterns of specification behavior. The rules are automatically applied to received telemetry and the inferred behaviors are available to ground operators using a visualization interface that makes it easier to understand and track spacecraft state. We describe initial results from applying our tool to telemetry received from the Curiosity rover currently roving the surface of Mars, where the visualizations are being used to trend subsystem behaviors, in order to identify potential problems before they happen. However, the technology is completely general and can be applied to any system that generates telemetry such as event logs.

  17. Comprehensive metabolomic profiling and incident cardiovascular disease: a systematic review

    Science.gov (United States)

    Background: Metabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (CVD). Methods and Results: We searched MEDLINE and EMBASE from inception to Janua...

  18. Bicuspid Aortic Valve Disease: A Comprehensive Review

    OpenAIRE

    Mordi, Ify; Tzemos, Nikolaos

    2012-01-01

    Bicuspid aortic valve is the commonest congenital cardiac abnormality in the general population. This paper article will discuss our current knowledge of the anatomy, pathophysiology, genetics, and clinical aspects of bicuspid aortic valve disease.

  19. 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.

  20. Erdheim-Chester disease: a comprehensive review.

    Science.gov (United States)

    Abdelfattah, Ahmed Maher; Arnaout, Karim; Tabbara, Imad A

    2014-07-01

    Erdheim-Chester disease is a rare form of non-Langerhans' cell histiocytosis characterized by multi-system infiltration by xanthogranulomas composed of foamy histiocytes surrounded by fibrosis. Approximately 400 cases have been reported in the literature, and the recent increase in the number of cases is likely due to the increased awareness of its associated morbidity and mortality. The etiology of this disease remains unknown, the clinical course is variable and treatment is still not well-established. The objective of this review is to describe the pathogenesis, clinical manifestations, and diagnosis of this rare disorder, and to review its prognosis and treatment. Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis. It was first described in 1930. Approximately 400 cases have been reported in the literature. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    Science.gov (United States)

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  2. Overlapping genetic and child-specific nonshared environmental influences on listening comprehension, reading motivation, and reading comprehension.

    Science.gov (United States)

    Schenker, Victoria J; Petrill, Stephen A

    2015-01-01

    This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Overlapping Genetic and Child-Specific Nonshared Environmental Influences on Listening Comprehension, Reading Motivation, and Reading Comprehension

    Science.gov (United States)

    Schenker, Victoria J.; Petrill, Stephen A.

    2015-01-01

    This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. PMID:26321677

  4. Specific Reading Comprehension Disability: Major Problem, Myth, or Misnomer?

    OpenAIRE

    Spencer, Mercedes; Quinn, Jamie M.; Wagner, Richard K.

    2014-01-01

    The goal of the present study was to test three competing hypotheses about the nature of comprehension problems of students who are poor in reading comprehension. Participants in the study were first, second, and third graders, totaling 9 cohorts and over 425,000 participants in all. The pattern of results was consistent across all cohorts: Less than one percent of first- through third-grade students who scored as poor in reading comprehension were adequate in both decoding and vocabulary. Al...

  5. Specific Reading Comprehension Disability: Major Problem, Myth, or Misnomer?

    Science.gov (United States)

    Spencer, Mercedes; Quinn, Jamie M.; Wagner, Richard K.

    2014-01-01

    The goal of the present study was to test three competing hypotheses about the nature of comprehension problems of students who are poor in reading comprehension. Participants in the study were first, second, and third graders, totaling nine cohorts and over 425,000 participants in all. The pattern of results was consistent across all cohorts:…

  6. CoViCAD : comprehensive visualization of coronary artery disease

    NARCIS (Netherlands)

    Temeer, M.; Olivan Bescos, J.; Breeuwer, M.; Vilanova, A.; Gerritsen, F.A.; Gröller, E.

    2007-01-01

    We present novel, comprehensive visualization techniques for the diagnosis of patients with Coronary Artery Disease using segmented cardiac MRI data. We extent an accepted medical visualization technique called the bull’s eye plot by removing discontinuities, preserving the volumetric nature of the

  7. Lymphocyte-predominant Hodgkin disease: a comprehensive overview.

    Science.gov (United States)

    Bose, Sumit; Ganesan, Chitra; Pant, Manish; Lai, Catherine; Tabbara, Imad A

    2013-02-01

    Lymphocyte-predominant Hodgkin disease is a rare form of Hodgkin lymphoma that is recognized as a separate histopathological entity. This disease tends to have multiple relapses, but has an overall good prognosis. Owing to its rarity, and the prolonged time period between recurrence and transformation events, there is no consensus regarding optimal management. However, the National Comprehensive Cancer Network guidelines indicate that for early stages, appropriate treatment is radiotherapy. Several management options have been reported including observation, radiation, chemotherapy, combined chemoradiotherapy, and anti-CD20 antibody therapy. Salvage therapy remains effective in inducing prolonged remission in patients with relapsed/refractory disease.

  8. A comprehensive test specification for pulse fission counters

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, D L [Control and Instrumentation Division, Atomic Energy Establishment, Winfrith, Dorchester, Dorset (United Kingdom)

    1962-02-15

    The following test specification is based on the memorandum AERE - M 728 which it now replaces It contains a standard acceptance test procedure for the many U.K.A.E.A, designed pulse fission counters now commercially available. This test specification may be used for any pulse fission counter provided a specification sheet as shown in Appendix 3 is supplied to the contractor quoting this report and including specified values for the measured quantities. (author)

  9. 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

  10. Specific learning disability in mathematics: a comprehensive review.

    Science.gov (United States)

    Soares, Neelkamal; Evans, Teresa; Patel, Dilip R

    2018-01-01

    Math skills are necessary for success in the childhood educational and future adult work environment. This article reviews the changing terminology for specific learning disabilities (SLD) in math and describes the emerging genetics and neuroimaging studies that relate to individuals with math disability (MD). It is important to maintain a developmental perspective on MD, as presentation changes with age, instruction, and the different models (educational and medical) of identification. Intervention requires a systematic approach to screening and remediation that has evolved with more evidence-based literature. Newer directions in behavioral, educational and novel interventions are described.

  11. Genetic background in nonalcoholic fatty liver disease: A comprehensive review

    Science.gov (United States)

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-01-01

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

  12. Determination and Application of Comprehensive Specific Frictional Resistance in Heating Engineering

    Directory of Open Access Journals (Sweden)

    Yanan Tian

    2018-01-01

    Full Text Available In this study, we analyze the deficiencies of specific frictional resistance in heating engineering. Based on economic specific frictional resistance, we put forward the concept of comprehensive specific frictional resistance, which considers the multiple factors of technology, economy, regulation modes, pipe segment differences, and medium pressure. Then, we establish a mathematical model of a heating network across its lifespan in order to develop a method for determining the comprehensive specific frictional resistance. Relevant conclusions can be drawn from the results. As an application, we have planned the heating engineering for Yangyuan County in China, which demonstrates the feasibility and superiority of the method.

  13. Eosinophils from Physiology to Disease: A Comprehensive Review

    Science.gov (United States)

    Yacoub, Mona-Rita; Ripa, Marco; Mannina, Daniele; Cariddi, Adriana; Saporiti, Nicoletta; Ciceri, Fabio; Castagna, Antonella; Dagna, Lorenzo

    2018-01-01

    Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances. PMID:29619379

  14. Syntactic comprehension and working memory in children with specific language impairment, autism or Down syndrome.

    Science.gov (United States)

    Fortunato-Tavares, Talita; Andrade, Claudia R F; Befi-Lopes, Debora; Limongi, Suelly O; Fernandes, Fernanda D M; Schwartz, Richard G

    2015-07-01

    This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance.

  15. A comprehensive review and update on Crohn's disease.

    Science.gov (United States)

    Gajendran, Mahesh; Loganathan, Priyadarshini; Catinella, Anthony P; Hashash, Jana G

    2018-02-01

    The term inflammatory bowel disease (IBD) refers principally to two major categories of chronic relapsing inflammatory intestinal disorders: Crohn's disease (CD) and ulcerative colitis (UC). In the United States, it is currently estimated that about 1.5 million people suffer from IBD, causing considerable suffering, mortality and economic loss every year. Yet the cause of IBD is unknown, and until we understand more, prevention or cure will not be possible. There is a lot of variation in the incidence and prevalence of CD based on geographic region, environment, immigrant population, and ethnic groups. The annual incidence of CD in North America is reported to be 3.1-20.2 per 100,000 with a prevalence of 201 per 100,000 population. Based on the epidemiological, genetic and immunological data, CD is considered to be a heterogeneous disorder with multifactorial etiology in which genetics and environment interact to manifest the disease. Several genes have been studied so for with respect to CD, but thus far the strong and replicated associations have been identified with NOD2, IL23R and ATG16L1 genes. The risk factors implicated with CD include smoking, low fiber- high carbohydrate diet, altered microbiome and medications such as non-steroidal anti-inflammatory drugs. CD is typically characterized by transmural inflammation of the intestine and could affect any part of the gastrointestinal tract from mouth to perianal area. In terms of distribution of the disease 25% of the patients have colitis only, 25% is ileitis only and 50% have ileocolitis. The Montreal classification is based on the age at diagnosis ( 40), disease location (Ileal, colonic, Ileocolonic) and the disease behavior (nonstricturing/nonpenetrating, stricturing, penetrating). The key features for diagnosing CD comprises a combination of radiographic, endoscopic and pathological findings demonstrating focal, asymmetric, transmural or granulomatous features. Abdominal Computed tomography (CT

  16. Comprehension of insincere communication in neurodegenerative disease: lies, sarcasm, and theory of mind.

    Science.gov (United States)

    Shany-Ur, Tal; Poorzand, Pardis; Grossman, Scott N; Growdon, Matthew E; Jang, Jung Y; Ketelle, Robin S; Miller, Bruce L; Rankin, Katherine P

    2012-01-01

    Comprehension of insincere communication is an important aspect of social cognition requiring visual perspective taking, emotion reading, and understanding others' thoughts, opinions, and intentions. Someone who is lying intends to hide their insincerity from the listener, while a sarcastic speaker wants the listener to recognize they are speaking insincerely. We investigated whether face-to-face testing of comprehending insincere communication would effectively discriminate among neurodegenerative disease patients with different patterns of real-life social deficits. We examined ability to comprehend lies and sarcasm from a third-person perspective, using contextual cues, in 102 patients with one of four neurodegenerative diseases (behavioral variant frontotemporal dementia [bvFTD], Alzheimer's disease [AD], progressive supranuclear palsy [PSP], and vascular cognitive impairment) and 77 healthy older adults (normal controls--NCs). Participants answered questions about videos depicting social interactions involving deceptive, sarcastic, or sincere speech using The Awareness of Social Inference Test. All subjects equally understood sincere remarks, but bvFTD patients displayed impaired comprehension of lies and sarcasm compared with NCs. In other groups, impairment was not disease-specific but was proportionate to general cognitive impairment. Analysis of the task components revealed that only bvFTD patients were impaired on perspective taking and emotion reading elements and that both bvFTD and PSP patients had impaired ability to represent others' opinions and intentions (i.e., theory of mind). Test performance correlated with informants' ratings of subjects' empathy, perspective taking and neuropsychiatric symptoms in everyday life. Comprehending insincere communication is complex and requires multiple cognitive and emotional processes vulnerable across neurodegenerative diseases. However, bvFTD patients show uniquely focal and severe impairments at every level

  17. Using Pupillometry to Investigate Sentence Comprehension in Children with and without Specific Language Impairment

    Science.gov (United States)

    Lum, Jarrad A. G.; Youssef, George J.; Clark, Gillian M.

    2017-01-01

    Purpose: In this study pupillometry was used to investigate the allocation of attentional resources associated with sentence comprehension in children with and without specific language impairment (SLI). Method: Eighteen children with SLI (age: M = 6.4 years) and 18 typically developing (TD) children (age: M = 6.3 years) participated in the study.…

  18. Complex Sentence Comprehension and Working Memory in Children with Specific Language Impairment

    Science.gov (United States)

    Montgomery, James W.; Evans, Julia L.

    2009-01-01

    Purpose: This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method: Twenty-four children with SLI, 18 age-matched…

  19. Subordinate clause comprehension and tense/agreement inconsistency in children with specific language impairment.

    Science.gov (United States)

    Souto, Sofía M; Leonard, Laurence B; Deevy, Patricia; Fey, Marc E; Bredin-Oja, Shelley L

    2016-01-01

    Several recent studies have suggested that the production errors of children with specific language impairment (SLI) such as The girl singing may be explained by a misinterpretation of grammatical adult input containing a similar structure (e.g., The boy hears the girl singing). Thirteen children with SLI and 13 younger typically developing children with comparable sentence comprehension test scores (TD-COMP) completed a comprehension task to assess their understanding of sentences involving a nonfinite subject-verb sequence in a subordinate clause such as The dad sees the boy running. TD-COMP children were more accurate on subordinate clause items than children with SLI despite similar performance on simple transitive (e.g., The horse sees the cow) and simple progressive (e.g., The cow is eating) items. However, no relationship was found between the SLI group's specific subordinate clause comprehension level and their specific level of auxiliary is production, casting some doubt on this type of structure as a source for inconsistent use of auxiliary is. The reader will learn that children with specific language impairment (SLI): (1) have difficulty understanding complex sentences that include nonfinite subject-verb sequences; (2) that this difficulty is apparent in comparison to younger typically developing peers who have similar scores not only on a sentence comprehension test, but also on simple sentences that correspond to the component parts of the complex sentences; and (3) that this weakness is concurrent with these children's inconsistent use of auxiliary is in production. Although novel verb studies show a clear connection between how children with SLI hear new verbs and how they use them, we do not yet have evidence that this connection is tied to a poor understanding of the input sentences that house the verbs. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Comprehensive analysis of the specificity of transcription activator-like effector nucleases

    DEFF Research Database (Denmark)

    Juillerat, Alexandre; Dubois, Gwendoline; Valton, Julien

    2014-01-01

    A key issue when designing and using DNA-targeting nucleases is specificity. Ideally, an optimal DNA-targeting tool has only one recognition site within a genomic sequence. In practice, however, almost all designer nucleases available today can accommodate one to several mutations within...... their target site. The ability to predict the specificity of targeting is thus highly desirable. Here, we describe the first comprehensive experimental study focused on the specificity of the four commonly used repeat variable diresidues (RVDs; NI:A, HD:C, NN:G and NG:T) incorporated in transcription activator......-like effector nucleases (TALEN). The analysis of >15 500 unique TALEN/DNA cleavage profiles allowed us to monitor the specificity gradient of the RVDs along a TALEN/DNA binding array and to present a specificity scoring matrix for RVD/nucleotide association. Furthermore, we report that TALEN can only...

  1. Comprehensive Care

    Science.gov (United States)

    ... Comprehensive Care Share this page Facebook Twitter Email Comprehensive Care Understand the importance of comprehensive MS care ... In this article A complex disease requires a comprehensive approach Today multiple sclerosis (MS) is not a ...

  2. Working memory and sentence comprehension of Hong Kong Chinese children with specific language impairment.

    Science.gov (United States)

    Siu, Elaine; Man, David W K

    2006-09-01

    Children with Specific Language Impairment present with delayed language development, but do not have a history of hearing impairment, mental deficiency, or associated social or behavioral problems. Non-word repetition was suggested as an index to reflect the capacity of phonological working memory. There is a paucity of such studies among Hong Kong Chinese children. This preliminary study aimed to examine the relationship between phonological working memory and Specific Language Impairment, through the processes of non-word repetition and sentence comprehension, of children with Specific Language Impairment and pre-school children with normal language development. Both groups of children were screened by a standardized language test. A list of Cantonese (the commonest dialect used in Hong Kong) multisyllabic nonsense utterances and a set of 18 sentences were developed for this study. t-tests and Pearson correlation were used to study the relationship between non-word repetition, working memory and specific language impairment. Twenty-three pre-school children with Specific Language Impairment (mean age = 68.30 months; SD = 6.90) and another 23 pre-school children (mean age = 67.30 months; SD = 6.16) participated in the study. Significant difference performance was found between the Specific Language Impairment group and normal language group in the multisyllabic nonsense utterances repetition task and the sentence comprehension task. Length effect was noted in Specific Language Impairment group children, which is consistent with the findings of other literature. In addition, correlations were also observed between the number of nonsense utterances repeated and the number of elements comprehended. Cantonese multisyllabic nonsense utterances might be worth further developing as a screening tool for the early detection of children with Specific Language Impairment.

  3. Can consumers trust web-based information about celiac disease? Accuracy, comprehensiveness, transparency, and readability of information on the internet.

    Science.gov (United States)

    McNally, Shawna L; Donohue, Michael C; Newton, Kimberly P; Ogletree, Sandra P; Conner, Kristen K; Ingegneri, Sarah E; Kagnoff, Martin F

    2012-04-04

    Celiac disease is an autoimmune disease that affects approximately 1% of the US population. Disease is characterized by damage to the small intestinal lining and malabsorption of nutrients. Celiac disease is activated in genetically susceptible individuals by dietary exposure to gluten in wheat and gluten-like proteins in rye and barley. Symptoms are diverse and include gastrointestinal and extraintestinal manifestations. Treatment requires strict adherence to a gluten-free diet. The Internet is a major source of health information about celiac disease. Nonetheless, information about celiac disease that is available on various websites often is questioned by patients and other health care professionals regarding its reliability and content. To determine the accuracy, comprehensiveness, transparency, and readability of information on 100 of the most widely accessed websites that provide information on celiac disease. Using the search term celiac disease, we analyzed 100 of the top English-language websites published by academic, commercial, nonprofit, and other professional (nonacademic) sources for accuracy, comprehensiveness, transparency, and reading grade level. Each site was assessed independently by 3 reviewers. Website accuracy and comprehensiveness were probed independently using a set of objective core information about celiac disease. We used 19 general criteria to assess website transparency. Website readability was determined by the Flesch-Kincaid reading grade level. Results for each parameter were analyzed independently. In addition, we weighted and combined parameters to generate an overall score, termed website quality. We included 98 websites in the final analysis. Of these, 47 (48%) provided specific information about celiac disease that was less than 95% accurate (ie, the predetermined cut-off considered a minimum acceptable level of accuracy). Independent of whether the information posted was accurate, 51 of 98 (52%) websites contained less than

  4. An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

    Directory of Open Access Journals (Sweden)

    Tobias Eisenberger

    Full Text Available Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs. Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.

  5. An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

    Science.gov (United States)

    Eisenberger, Tobias; Decker, Christian; Hiersche, Milan; Hamann, Ruben C; Decker, Eva; Neuber, Steffen; Frank, Valeska; Bolz, Hanno J; Fehrenbach, Henry; Pape, Lars; Toenshoff, Burkhard; Mache, Christoph; Latta, Kay; Bergmann, Carsten

    2015-01-01

    Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs). Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.

  6. The specific role of inhibition in reading comprehension in good and poor comprehenders.

    Science.gov (United States)

    Borella, Erika; Carretti, Barbara; Pelegrina, Santiago

    2010-01-01

    Difficulties in inhibitory processes have been shown to characterize the performance of poor comprehenders. However, the inhibitory inefficiency of poor comprehenders is most often assessed by their resistance to proactive interference, that is, the ability to suppress off-goal task information from working memory (WM). In two studies tasks assessing resistance to proactive interference (intrusion errors), response to distracters (Text With Distracters task) and prepotent response inhibition (Stroop and Hayling tests), along with WM measures, were administered to children aged 10 to 11, both good and poor comprehenders. The aim of the study was to specifically determine whether general or specific inhibitory factors affect poor comprehenders' reading difficulties. Results showed that poor comprehenders, compared to good ones, are impaired in WM tasks and in inhibitory tasks that assess resistance to proactive interference. This suggests that reading comprehension difficulties of poor comprehenders are related to specific inhibitory problems.

  7. 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...

  8. Improving listening comprehension skills relying on metacognitive strategies - focus on vocabulary and specific l2 instruction

    Directory of Open Access Journals (Sweden)

    Jerotijević-Tišma Danica

    2016-01-01

    Full Text Available The present paper aims at investigating the application of an instructional method specifically focused on the expansion of metacognitive awareness and its effect on Serbian EFL students’ listening comprehension. The current study is a follow-up research of a similar study by Vandergrift and Tafaghodtari (2010. However, we sought to expand the previous research by investigating the relationship between the students’ current level of L2 (target language vocabulary and listening test scores. Our study likewise differed in the sample of participants, the target language, teaching and testing material used, and the duration of the very experiment. To answer the proposed research questions we conducted an experiment with 57 Serbian secondary school EFL (English as a Foreign Language learners divided into experimental (n=27 and control group (n=30. The results of the pre- and post-tests of the two groups showed the beneficial effects of developing metacognitive strategies and the strong positive correlation between the level of vocabulary and listening comprehension. The paper underlines important pedagogical implications especially regarding the enhancement of metacognitive awareness and vocabulary proficiency of students in order to improve performance on listening comprehension tasks.

  9. High throughput protease profiling comprehensively defines active site specificity for thrombin and ADAMTS13.

    Science.gov (United States)

    Kretz, Colin A; Tomberg, Kärt; Van Esbroeck, Alexander; Yee, Andrew; Ginsburg, David

    2018-02-12

    We have combined random 6 amino acid substrate phage display with high throughput sequencing to comprehensively define the active site specificity of the serine protease thrombin and the metalloprotease ADAMTS13. The substrate motif for thrombin was determined by >6,700 cleaved peptides, and was highly concordant with previous studies. In contrast, ADAMTS13 cleaved only 96 peptides (out of >10 7 sequences), with no apparent consensus motif. However, when the hexapeptide library was substituted into the P3-P3' interval of VWF73, an exosite-engaging substrate of ADAMTS13, 1670 unique peptides were cleaved. ADAMTS13 exhibited a general preference for aliphatic amino acids throughout the P3-P3' interval, except at P2 where Arg was tolerated. The cleaved peptides assembled into a motif dominated by P3 Leu, and bulky aliphatic residues at P1 and P1'. Overall, the P3-P2' amino acid sequence of von Willebrand Factor appears optimally evolved for ADAMTS13 recognition. These data confirm the critical role of exosite engagement for substrates to gain access to the active site of ADAMTS13, and define the substrate recognition motif for ADAMTS13. Combining substrate phage display with high throughput sequencing is a powerful approach for comprehensively defining the active site specificity of proteases.

  10. Dietary sodium in chronic kidney disease: a comprehensive approach.

    Science.gov (United States)

    Wright, Julie A; Cavanaugh, Kerri L

    2010-01-01

    Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake.

  11. The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review

    Science.gov (United States)

    Di Piazza, Ambra; Costanzo, Massimo; Scopelliti, Laura; Salvaggi, Francesco; Cupido, Francesco; Salerno, Sergio; Lo Casto, Antonio; Midiri, Massimo; Lo Re, Giuseppe; Lagalla, Roberto

    2017-01-01

    Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%–80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients. PMID:28706536

  12. 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.

  13. Role of Working Memory in Explaining the Performance of Individuals with Specific Reading Comprehension Difficulties: A Meta-Analysis

    Science.gov (United States)

    Carretti, Barbara; Borella, Erika; Cornoldi, Cesare; De Beni, Rossana

    2009-01-01

    It is well established that working memory is related to reading comprehension ability. However, its role in explaining specific reading comprehension difficulties is still under debate: the issue mainly concerns whether the contribution of working memory is dependent on task modality (verbal tasks being more predictive than visuo-spatial tasks)…

  14. The comprehension of Italian relative clauses in poor readers and in children with Specific Language Impairment

    Directory of Open Access Journals (Sweden)

    Fabrizio Arosio

    2017-02-01

    Full Text Available Children with Specific Language Impairment (SLI and children with Developmental Dyslexia (DD have problems comprehending relative clauses (RCs and find object RCs more difficult than subject RCs, as do typically developing children. Few studies have compared these groups directly, leaving it unclear whether the problems observed in children with DD are similar to those described in SLI. Work with typically developing children has shown that the comprehension of passive RCs is less challenging than that of object RCs. It is argued that this asymmetry depends on intervention effects as modelized in a Relativized Minimality framework. Since movement is challenging for children with SLI and those with DD, examining and comparing their comprehension of object RCs and passive RCs can broaden our understanding of their language deficits. In fact, both structures involve movement, but the moved element and the movement configuration are different. In our study we investigated the comprehension of subject RCs, object RCs and passive RCs in 12 Italian monolingual children with SLI (mean age: 7;6, 13 Italian monolingual children with DD (mean age: 10;7 and 50 typically developing controls matched for age, grammar and vocabulary. Results from a picture selection task show that: (i subject RCs are unproblematic for all children; (ii object RCs are challenging for children with SLI, children with DD and younger typically developing controls; (iii passive RCs are better understood than object RCs in all groups, but still problematic for children with SLI and younger typically developing controls. Our data show that intervention effects are found in children with SLI and children with DD and that those with SLI have a deficit in transferring thematic roles to moved elements. Our results point out that some of the children with DD have a mild grammatical deficit that was undetected or escaped standardized tests.

  15. Acute Graft Versus Host Disease: A Comprehensive Review.

    Science.gov (United States)

    Nassereddine, Samah; Rafei, Hind; Elbahesh, Ehab; Tabbara, Imad

    2017-04-01

    Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT). Over the last five years, the progress in understanding the pathophysiology of this immune based-process helped redefine graft versus host reaction and opened new possibilities for novel preventive and therapeutic approaches. The evolution in the field of immunology widened the horizons for hematopoietic stem cell transplant leading to the availability of different stem cell sources for potential graft and incorporation of novel conditioning regimens. There is conflicting data about the impact of the graft source and the conditioning regimen used in the process of AHSCT on the incidence of aGVHD. Many studies have reported increased risk of chronic GVHD (cGVHD) and to a less extent aGVHD with the use of peripheral blood stem cell and bone marrow compared to umbilical cord stem cell. The conditioning regimen, either myeloablative, non-myeloablative or reduced intensity may have different impact on the incidence of GVHD. Several preventive modalities have been adopted by different transplant centers but, to date, there is no standardized regimen. As for treatment, immunosuppression using steroids remains the first line of intervention. Several novel therapeutic options are being investigated for treatment of steroid-refractory aGVHD including the use of mesenchymal stem cells, anti thymocyte globulin and extra corporeal photophoresis. This review discusses the pathophysiology, risk factors, clinical features, and advances in the diagnosis, prevention and treatment of aGVHD. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome.

    Science.gov (United States)

    Wlodarski, Tomasz; Kutner, Jan; Towpik, Joanna; Knizewski, Lukasz; Rychlewski, Leszek; Kudlicki, Andrzej; Rowicka, Maga; Dziembowski, Andrzej; Ginalski, Krzysztof

    2011-01-01

    Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity.

  17. Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome.

    Directory of Open Access Journals (Sweden)

    Tomasz Wlodarski

    Full Text Available Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity. Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity.

  18. Comprehension of metaphors and idioms in patients with Alzheimer's disease: a longitudinal study.

    Science.gov (United States)

    Papagno, C

    2001-07-01

    Language in patients with Alzheimer's disease has been extensively studied, with the exception of non-literal language comprehension. However, in our speech, we often make use of expressions, which are not necessarily interpreted on a literal ground. Comprehension of metaphors and idioms was examined in 39 patients with probable early Alzheimer's disease. The results showed that the decline of figurative language is not an early symptom of dementia and can occur independently from the impairment of propositional language. It was also found that metaphors and idioms differ as far as the predominant kind of error is concerned.

  19. 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

  20. 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

  1. A comprehensive questionnaire for the assessment of health-related quality of life in coeliac disease (CDQL).

    Science.gov (United States)

    Skjerning, Halfdan; Hourihane, Jonathan; Husby, Steffen; DunnGalvin, Audrey

    2017-10-01

    Coeliac disease (CD) is a chronic immune-mediated disease in genetically susceptible individuals, induced by ingested gluten. The treatment for CD is a lifelong gluten-free diet (GFD). The GFD involves restrictions in diet that may impact on a person's Health-Related Quality of Life (HRQoL). The aim of the present study was to develop the Coeliac Disease Quality of Life questionnaire (CDQL): a comprehensive CD-specific HRQoL measure that can be completed by children, adolescents, and adults or by proxy. The questionnaire was developed in three phases. In phase 1, focus group methods and qualitative analysis of verbatim transcripts generated CD-specific items for a prototype instrument to sensitively captured patient concerns. In phase 2, CD patients completed the prototype CDQL. The questionnaire was refined through analysis of data and cognitive interviewing. In phase 3, the final version of the CDQL was answered by Danish respondents. The psychometric properties of the CDQL were assessed, and the HRQoL data were analyzed. The CDQL was completed by 422 respondents. The CDQL has 12 patient background items, 2 generic HRQoL items, and 30 CD-specific HRQoL item. The CD-specific HRQoL items were distributed on eight scales with acceptable to excellent reliability. Comprehensiveness and understandability was shown by feedback from cognitive interviewing from children, adolescents, and adults. Content validity was ensured by involving patients and clinicians in the development of the questionnaire. Sensitivity of the questionnaire was demonstrated in differences found between children, adolescents, and adult's perception of their HRQoL in relation to having CD. The CDQL comprehensively measures HRQoL in CD, and is psychometrically robust. The questionnaire may prove useful in tracking HRQoL in CD across age groups.

  2. 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...

  3. Framework for Infectious Disease Analysis: A comprehensive and integrative multi-modeling approach to disease prediction and management.

    Science.gov (United States)

    Erraguntla, Madhav; Zapletal, Josef; Lawley, Mark

    2017-12-01

    The impact of infectious disease on human populations is a function of many factors including environmental conditions, vector dynamics, transmission mechanics, social and cultural behaviors, and public policy. A comprehensive framework for disease management must fully connect the complete disease lifecycle, including emergence from reservoir populations, zoonotic vector transmission, and impact on human societies. The Framework for Infectious Disease Analysis is a software environment and conceptual architecture for data integration, situational awareness, visualization, prediction, and intervention assessment. Framework for Infectious Disease Analysis automatically collects biosurveillance data using natural language processing, integrates structured and unstructured data from multiple sources, applies advanced machine learning, and uses multi-modeling for analyzing disease dynamics and testing interventions in complex, heterogeneous populations. In the illustrative case studies, natural language processing from social media, news feeds, and websites was used for information extraction, biosurveillance, and situation awareness. Classification machine learning algorithms (support vector machines, random forests, and boosting) were used for disease predictions.

  4. Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease.

    NARCIS (Netherlands)

    Monninkhof, E.M.; Valk, P.D.L.P.M. van der; Palen, J.A.M. van der; Herwaarden, C.L.A. van; Zielhuis, G.A.

    2003-01-01

    The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life (HRQoL), symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease (COPD). This study was part of the overall COPD

  5. 78 FR 8535 - Medicare Program: Comprehensive End-Stage Renal Disease Care Model Announcement

    Science.gov (United States)

    2013-02-06

    ... develop and test innovative health care payment and service delivery models that show promise of reducing... test innovative payment and service delivery models that reduce spending under Medicare, Medicaid or...] Medicare Program: Comprehensive End-Stage Renal Disease Care Model Announcement AGENCY: Centers for...

  6. 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.

  7. 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.

  8. "Reading" Paintings: Evidence for Trans-Symbolic and Symbol-Specific Comprehension Processes

    Science.gov (United States)

    Loughlin, Sandra; Grossnickle, Emily; Dinsmore, Daniel; Alexander, Patricia

    2015-01-01

    Art-based reading instruction and interventions for elementary and middle school students are growing in popularity despite scant theoretical rationale and empirical research support. This study explored the degree to which painting comprehension processes map onto text comprehension processes in this population. In particular, we used think aloud…

  9. Hypertext comprehension of deaf and hard-of-hearing students and students with specific language impairment

    NARCIS (Netherlands)

    Blom, H.C.; Segers, P.C.J.; Hermans, D.; Knoors, H.E.T.; Verhoeven, L.T.W.

    2017-01-01

    This paper provides insight into the reading comprehension of hierarchically structured hypertexts within D/HH students and students with SLI. To our knowledge, it is the first study on hypertext comprehension in D/HH students and students with SLI, and it also considers the role of working memory.

  10. Can Consumers Trust Web-Based Information About Celiac Disease? Accuracy, Comprehensiveness, Transparency, and Readability of Information on the Internet

    Science.gov (United States)

    McNally, Shawna L; Donohue, Michael C; Newton, Kimberly P; Ogletree, Sandra P; Conner, Kristen K; Ingegneri, Sarah E

    2012-01-01

    Background Celiac disease is an autoimmune disease that affects approximately 1% of the US population. Disease is characterized by damage to the small intestinal lining and malabsorption of nutrients. Celiac disease is activated in genetically susceptible individuals by dietary exposure to gluten in wheat and gluten-like proteins in rye and barley. Symptoms are diverse and include gastrointestinal and extraintestinal manifestations. Treatment requires strict adherence to a gluten-free diet. The Internet is a major source of health information about celiac disease. Nonetheless, information about celiac disease that is available on various websites often is questioned by patients and other health care professionals regarding its reliability and content. Objectives To determine the accuracy, comprehensiveness, transparency, and readability of information on 100 of the most widely accessed websites that provide information on celiac disease. Methods Using the search term celiac disease, we analyzed 100 of the top English-language websites published by academic, commercial, nonprofit, and other professional (nonacademic) sources for accuracy, comprehensiveness, transparency, and reading grade level. Each site was assessed independently by 3 reviewers. Website accuracy and comprehensiveness were probed independently using a set of objective core information about celiac disease. We used 19 general criteria to assess website transparency. Website readability was determined by the Flesch-Kincaid reading grade level. Results for each parameter were analyzed independently. In addition, we weighted and combined parameters to generate an overall score, termed website quality. Results We included 98 websites in the final analysis. Of these, 47 (48%) provided specific information about celiac disease that was less than 95% accurate (ie, the predetermined cut-off considered a minimum acceptable level of accuracy). Independent of whether the information posted was accurate, 51 of

  11. [Evaluation on intervention measures of comprehensive control for parasitic diseases in demonstration plot of Xiangyun County].

    Science.gov (United States)

    Wen-Juan, Li; Shao-Rong, Chen; Yan-Hong, Li; Wen, Fang; Chun-Rong, Ke; Li-Bo, Wang

    2011-10-01

    To evaluate the effect of comprehensive intervention measures to control and prevent parasitic diseases in the demonstration plot of Xiangyun County, so as to provide the evidence for establishing appropriate measures of parasitic diseases control and prevention. The baseline data of soil-transmitted nematode infections were obtained in 2006. A series of intervention measures, including health education, deworming, drinking water improvement,latrine improvement, and environment reconstruction, were performed for three years and the effect of the comprehensive intervention measures was evaluated by the national expert group in 2009. The awareness rate of parasitic disease knowledge of residents in 2009 (86.96%) was significantly higher than that in 2006 (35.20%) (Chi2 = 122.95, P transmitted nematode infections, the infection rates of Ascaris lumbricoides in both 2006 and 2009 were the highest and the rates were 18.74% and 2.08%, respectively. In the demonstration plots for parasitic diseases control and prevention of Xiangyun County, the effect of the comprehensive intervention measures which take health education as the forerunner and give priority to control source of parasite infection is remarkable. The measures implemented can achieve the purpose to reduce the infection rates of parasites and improve human health.

  12. Hypertext comprehension of deaf and hard-of-hearing students and students with specific language impairment.

    Science.gov (United States)

    Blom, Helen; Segers, Eliane; Hermans, Daan; Knoors, Harry; Verhoeven, Ludo

    2017-02-01

    This paper provides insight into the reading comprehension of hierarchically structured hypertexts within D/HH students and students with SLI. To our knowledge, it is the first study on hypertext comprehension in D/HH students and students with SLI, and it also considers the role of working memory. We compared hypertext versus linear text comprehension in D/HH students and students with SLI versus younger students without language problems who had a similar level of decoding and vocabulary. The results demonstrated no difference in text comprehension between the hierarchically structured hypertext and the linear text. Text comprehension of D/HH students and students with SLI was comparable to that of the students without language problems. In addition, there was a similar positive predictive value of visuospatial and not verbal working memory on hypertext comprehension for all three groups. The findings implicate that educational settings can make use of hierarchically structured hypertexts as well as linear texts and that children can navigate in the digital world from young age on, even if language or working memory problems are present. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. The Effect of Neuro-Linguistic Programming (NLP) on Reading Comprehension in English for Specific Purposes Courses

    Science.gov (United States)

    Farahani, Fahimeh

    2018-01-01

    Neuro-Linguistic Programming (NLP) has potential to help language learners; however, it has received scant attention. The present study was an attempt to investigate the effect of NLP techniques on reading comprehension of English as a Foreign Language (EFL) learners at an English for Specific Purposes (ESP) course. To achieve this goal, two…

  14. 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)....

  15. The specificity of emotion inferences in text comprehension: the role of top-down and bottom-up processes

    OpenAIRE

    Gillioz, Christelle; Gygax, Pascal

    2013-01-01

    The aim of this thesis was to investigate the influence of individual differences and the nature of the information presented to readers on emotion inferences in text comprehension, in particular on the specificity of these emotion inferences. Research on emotion inferences has led some researchers to suggest that emotion inferences made during reading are specific (e.g., Gernsbacher et al., 1992) whereas others (e.g., Gygax et al., 2007) proposed that readers do not need to elaborate a compl...

  16. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy

    Science.gov (United States)

    Satoh, Minoru; Tanaka, Shin; Ceribelli, Angela; Calise, S. John; Chan, Edward K. L.

    2018-01-01

    Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a unique clinical subset of PM/DM, making them useful in predicting and monitoring certain clinical manifestations. Classic MSAs known for over 30 years include antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP). Anti-Jo-1 is the first autoantibodies to ARS detected in 15–25 % of patients. In addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS) have been reported with prevalence, usually 1–5 % or lower. Patients with any antiARS antibodies are associated with anti-synthetase syndrome characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud’s phenomenon, and others. Several recent studies suggested heterogeneity in clinical features among different anti-ARS antibody-positive patients and anti-ARS may also be found in idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and associated with good response to steroid treatment and good prognosis. Anti-SRP is specific for PM and associated with treatment-resistant myopathy histologically characterized as necrotizing myopathy. In addition to classic MSAs, several new autoantibodies with strong clinical significance have been described in DM. Antibodies to transcription intermediary factor 1γ/α (TIF1γ/α, p155/140) are frequently found in DM associated with malignancy while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are associated with clinically amyopathic DM (CADM) complicated by rapidly progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new DM-specific autoantibodies. Addition of

  17. 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.

  18. 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.

  19. A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration

    OpenAIRE

    Rivera, Andrea; White, Karen; Stöhr, Heidi; Steiner, Klaus; Hemmrich, Nadine; Grimm, Timo; Jurklies, Bernhard; Lorenz, Birgit; Scholl, Hendrik P. N.; Apfelstedt-Sylla, Eckhart; Weber, Bernhard H. F.

    2000-01-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in ...

  20. Validation of the Comprehensive ICF Core Set for obstructive pulmonary diseases from the perspective of physiotherapists.

    Science.gov (United States)

    Rauch, Alexandra; Kirchberger, Inge; Stucki, Gerold; Cieza, Alarcos

    2009-12-01

    The 'Comprehensive ICF Core Set for obstructive pulmonary diseases' (OPD) is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with OPD. To optimize a multidisciplinary and patient-oriented approach in pulmonary rehabilitation, in which physiotherapy plays an important role, the ICF offers a standardized language and understanding of functioning. For it to be a useful tool for physiotherapists in rehabilitation of patients with OPD, the objective of this study was to validate this Comprehensive ICF Core Set for OPD from the perspective of physiotherapists. A three-round survey based on the Delphi technique of physiotherapists who are experienced in the treatment of OPD asked about the problems, resources and aspects of environment of patients with OPD that physiotherapists treat in clinical practice (physiotherapy intervention categories). Responses were linked to the ICF and compared with the existing Comprehensive ICF Core Set for OPD. Fifty-one physiotherapists from 18 countries named 904 single terms that were linked to 124 ICF categories, 9 personal factors and 16 'not classified' concepts. The identified ICF categories were mainly third-level categories compared with mainly second-level categories of the Comprehensive ICF Core Set for OPD. Seventy of the ICF categories, all personal factors and 15 'not classified' concepts gained more than 75% agreement among the physiotherapists. Of these ICF categories, 55 (78.5%) were covered by the Comprehensive ICF Core Set for OPD. The validity of the Comprehensive ICF Core Set for OPD was largely supported by the physiotherapists. Nevertheless, ICF categories that were not covered, personal factors and not classified terms offer opportunities towards the final ICF Core Set for OPD and further research to strengthen physiotherapists' perspective in pulmonary rehabilitation.

  1. 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.

  2. Assessing reading comprehension in adolescent low achievers : Subskills identification and task specificity

    NARCIS (Netherlands)

    van Steensel, R.; Oostdam, R.; van Gelderen, A.

    2013-01-01

    On the basis of a validation study of a new test for assessing low-achieving adolescents’ reading comprehension skills – the SALT-reading – we analyzed two issues relevant to the field of reading test development. Using the test results of 200 seventh graders, we examined the possibility of

  3. Reading comprehension as part of the teaching learning process of English for specific purposes

    Directory of Open Access Journals (Sweden)

    Yaima Rosa Reyes Piñero

    2012-06-01

    Full Text Available This article presents and characterizes a system of interdisciplinary tasks which contributes to reading comprehension as a basic objective of the teaching learning process of English in the first year students of Marxism-Leninism and History career of the University of Pedagogical Sciences in Pinar del Río.

  4. Hidden Language Impairments in Children: Parallels between Poor Reading Comprehension and Specific Language Impairment?

    Science.gov (United States)

    Nation, Kate; Clarke, Paula; Marshall, Catherine M.; Durand, Marianne

    2004-01-01

    This study investigates the oral language skills of 8-year-old children with impaired reading comprehension. Despite fluent and accurate reading and normal nonverbal ability, these children are poor at understanding what they have read. Tasks tapping 3 domains of oral language, namely phonology, semantics, and morphosyntax, were administered,…

  5. 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....

  6. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review.

    Science.gov (United States)

    Atzeni, Fabiola; Gerardi, Maria Chiara; Barilaro, Giuseppe; Masala, Ignazio Francesco; Benucci, Maurizio; Sarzi-Puttini, Piercarlo

    2018-01-01

    Interstitial lung diseases (ILDs) are among the most serious complications associated with systemic rheumatic diseases, and lead to significant morbidity and mortality; they may also be the first manifestation of connective tissue diseases (CTDs). The aim of this narrative review is to summarise the data concerning the pathogenesis of CTD/ILD and its distinguishing features in different rheumatic diseseas. Areas covered: The pathogenesis, clinical aspects and treatment of ILD associated with rheumatic systemic diseases and CTDs were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1995 and February 2017 using combinations of words or terms. Articles not written in English were excluded. Expert commentary: The management of CTD-ILD is challenging because of the lack of robust data regarding the treatments used, the heterogeneity of the diseases themselves, and the scarcity of well-defined outcome measures. Treatment decisions are often made clinically on the basis of functional, radiographic progression, and exacerbating factors such as age and the burden of comorbidities. Given the complexities of diagnosis and the paucity of treatment trials, the management of CTD patients with ILD requires multidisciplinary collaboration between rheumatologists and pulmonologists in CTD-ILD clinics.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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

  18. Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

    OpenAIRE

    Lauer, Georg M.; Ouchi, Kei; Chung, Raymond T.; Nguyen, Tam N.; Day, Cheryl L.; Purkis, Deborah R.; Reiser, Markus; Kim, Arthur Y.; Lucas, Michaela; Klenerman, Paul; Walker, Bruce D.

    2002-01-01

    The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel...

  19. Quality of life and symptoms in patients with malignant diseases admitted to a comprehensive cancer centre

    DEFF Research Database (Denmark)

    Strömgren, Lene Annette Sand; Niemann, Carsten Utoft; Tange, Ulla Brix

    2014-01-01

    PURPOSE: Quality of life and symptomatology in patients with malignancies admitted to comprehensive cancer centres are rarely investigated. Thus, this study aimed to investigate symptomatology and health-related quality of life of inpatients with cancer. METHODS: A prospective, cross......-sample test, rank tests and Fisher's exact test. RESULTS: One hundred twenty-four patients were analysed, mean age = 59 years (SD = 13.7), 42 % admitted to haematological department; lung cancer was the most frequent diagnosis (15 %). Low health-related quality of life and severe symptom burden, especially...... in oncology patients (P = 0.0194 and 0.0064, respectively). CONCLUSIONS: Patients in the wards of haematology and oncology had pronounced symptomatology and low quality of life. A more systematic focus on the amelioration of problems with functioning and symptoms among inpatients with malignant diseases...

  20. 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.

  1. Screening for sequence-specific RNA-BPs by comprehensive UV crosslinking

    Directory of Open Access Journals (Sweden)

    Le Meuth-Metzinger Valerie

    2002-06-01

    Full Text Available Abstract Background Specific cis-elements and the associated trans-acting factors have been implicated in the post-transcriptional regulation of gene expression. In the era of genome wide analyses identifying novel trans-acting factors and cis-regulatory elements is a step towards understanding coordinated gene expression. UV-crosslink analysis is a standard method used to identify RNA-binding proteins. Uridine is traditionally used to radiolabel substrate RNAs, however, proteins binding to cis-elments particularly uridine poor will be weakly or not detected. We evaluate here the possibility of using UV-crosslinking with RNA substrates radiolabeled with each of the four ribonucleotides as an approach for screening for novel sequence specific RNA-binding proteins. Results The radiolabeled RNA substrates were derived from the 3'UTRs of the cloned Eg and c-mos Xenopus laevis maternal mRNAs. Specific, but not identical, uv-crosslinking signals were obtained, some of which corresponded to already identified proteins. A signal for a novel 90 kDa protein was observed with the c-mos 3'UTR radiolabeled with both CTP and GTP but not with UTP. The binding site of the 90 kDa RNA-binding protein was localised to a 59-nucleotide portion of the c-mos 3'UTR. Conclusion That the 90 kDa signal was detected with RNAs radiolabeled with CTP or GTP but not UTP illustrates the advantage of radiolabeling all four nucleotides in a UV-crosslink based screen. This method can be used for both long and short RNAs and does not require knowledge of the cis-acting sequence. It should be amenable to high throughput screening for RNA binding proteins.

  2. Physiotherapy scoliosis-specific exercises - a comprehensive review of seven major schools.

    Science.gov (United States)

    Berdishevsky, Hagit; Lebel, Victoria Ashley; Bettany-Saltikov, Josette; Rigo, Manuel; Lebel, Andrea; Hennes, Axel; Romano, Michele; Białek, Marianna; M'hango, Andrzej; Betts, Tony; de Mauroy, Jean Claude; Durmala, Jacek

    2016-01-01

    In recent decades, there has been a call for change among all stakeholders involved in scoliosis management. Parents of children with scoliosis have complained about the so-called "wait and see" approach that far too many doctors use when evaluating children's scoliosis curves between 10° and 25°. Observation, Physiotherapy Scoliosis Specific Exercises (PSSE) and bracing for idiopathic scoliosis during growth are all therapeutic interventions accepted by the 2011 International Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT). The standard features of these interventions are: 1) 3-dimension self-correction; 2) Training activities of daily living (ADL); and 3) Stabilization of the corrected posture. PSSE is part of a scoliosis care model that includes scoliosis specific education, scoliosis specific physical therapy exercises, observation or surveillance, psychological support and intervention, bracing and surgery. The model is oriented to the patient. Diagnosis and patient evaluation is essential in this model looking at a patient-oriented decision according to clinical experience, scientific evidence and patient's preference. Thus, specific exercises are not considered as an alternative to bracing or surgery but as a therapeutic intervention, which can be used alone or in combination with bracing or surgery according to individual indication. In the PSSE model it is recommended that the physical therapist work as part of a multidisciplinary team including the orthopeadic doctor, the orthotist, and the mental health care provider - all are according to the SOSORT guidelines and Scoliosis Research Society (SRS) philosophy. From clinical experiences, PSSE can temporarily stabilize progressive scoliosis curves during the secondary period of progression, more than a year after passing the peak of growth. In non-progressive scoliosis, the regular practice of PSSE could produce a temporary and significant reduction of the Cobb angle. PSSE can also

  3. Comprehensive molecular diagnosis of Epstein-Barr virus-associated lymphoproliferative diseases using next-generation sequencing.

    Science.gov (United States)

    Ono, Shintaro; Nakayama, Manabu; Kanegane, Hirokazu; Hoshino, Akihiro; Shimodera, Saeko; Shibata, Hirofumi; Fujino, Hisanori; Fujino, Takahiro; Yunomae, Yuta; Okano, Tsubasa; Yamashita, Motoi; Yasumi, Takahiro; Izawa, Kazushi; Takagi, Masatoshi; Imai, Kohsuke; Zhang, Kejian; Marsh, Rebecca; Picard, Capucine; Latour, Sylvain; Ohara, Osamu; Morio, Tomohiro

    2018-05-18

    Epstein-Barr virus (EBV) is associated with several life-threatening diseases, such as lymphoproliferative disease (LPD), particularly in immunocompromised hosts. Some categories of primary immunodeficiency diseases (PIDs) including X-linked lymphoproliferative syndrome (XLP), are characterized by susceptibility and vulnerability to EBV infection. The number of genetically defined PIDs is rapidly increasing, and clinical genetic testing plays an important role in establishing a definitive diagnosis. Whole-exome sequencing is performed for diagnosing rare genetic diseases, but is both expensive and time-consuming. Low-cost, high-throughput gene analysis systems are thus necessary. We developed a comprehensive molecular diagnostic method using a two-step tailed polymerase chain reaction (PCR) and a next-generation sequencing (NGS) platform to detect mutations in 23 candidate genes responsible for XLP or XLP-like diseases. Samples from 19 patients suspected of having EBV-associated LPD were used in this comprehensive molecular diagnosis. Causative gene mutations (involving PRF1 and SH2D1A) were detected in two of the 19 patients studied. This comprehensive diagnosis method effectively detected mutations in all coding exons of 23 genes with sufficient read numbers for each amplicon. This comprehensive molecular diagnostic method using PCR and NGS provides a rapid, accurate, low-cost diagnosis for patients with XLP or XLP-like diseases.

  4. Comprehensive Diabetes and Non-Communicable Disease Educator in the Low-Resource Settings.

    Science.gov (United States)

    Bhattarai, M D

    2016-01-01

    The role of self-management education in diabetes and other major non-communicable diseases is clearly evident. To take care of and educate people with diabetes and other major NCD under the supervision of medical professionals and for education of other health care professionals, Comprehensive Diabetes and NCD Educators are needed in the routine service in peripheral health clinics and hospitals. The areas of training of CDNCD educator should match with the cost-effective interventions for diabetes and other major NCD that are feasible and planned for implementation in primary care in the low resource settings. Most of such interventions are part of diabetes education as required for Diabetes Self-Management Education programmes and traditional Diabetes Educator. The addition of use of inhaled steroids and bronchodilator in chronic respiratory disease and identification of presenting features of cancer, also required for many people with diabetes with various such common co-morbidities, will complete the areas of training of traditional Diabetes Educator as that of CDNCD Educator. Staff nurse and health assistants, who are as such already providing routine clinical service to all patients including with diabetes and major NCD in peripheral health clinics and hospitals, are most appropriate for CDNCD Educator training. The training of CDNCD Educator, like that of traditional Diabetes Educator, requires fulfilment of sufficient hours of practical work experience under supervision and achievement of the essential competencies entailing at least 6 month or more of intensive training schedules to be eligible to appear in its final certifying examination.

  5. Specific toxicity after stereotactic body radiation therapy to the central chest. A comprehensive review

    Energy Technology Data Exchange (ETDEWEB)

    Oskan, Feras; Becker, Gerd; Bleif, Martin [Alb-Fils Kliniken GmbH, Department of Radiation Oncology, Goeppingen (Germany); CyberKnife Suedwest Centre, Radiochirurgicum, Goeppingen (Germany)

    2017-03-15

    The toxicity of stereotactic body radiation therapy in the central chest remains an unsettled issue. The collected data concerning the observed complications are poorly understood and are limited in their quantity and quality, thus hampering a precise delineation of treatment-specific toxicity. The majority of complications scored as toxicity grade 5, namely respiratory failure and fatal hemoptysis, are most likely related to multiple competing risks and occurred at different dose fractionation schemas, e. g., 10-12 fractions of 4-5 Gy, 5 fractions of 10 Gy, 3 fractions of 20-22 Gy, and 1 fraction of 15-30 Gy. Further investigations with longer follow-up and more details of patients' pretreatment and tumor characteristics are required. Furthermore, satisfactory documentation of complications and details of dosimetric parameters, as well as limitation of the wide range of possible fractionation schemes is also warranted for a better understanding of the risk factors relevant for macroscopic damage to the serially organized anatomic structure within the central chest. (orig.) [German] Das Risiko fuer schwere Nebenwirkungen der stereotaktischen Strahlentherapie bei zentralen Lungentumoren ist bisher schlecht definiert. Nicht nur die begrenzte Zahl der dokumentierten Ereignisse, sondern auch die Vielzahl der verwendeten Fraktionierungsschemata erschwert das Herausarbeiten valider prognostischer Faktoren. Auf Basis dieser Datenlage laesst sich das Risiko fuer Grad-5-Toxizitaeten, insbesondere Atemversagen und toedliche Blutungen, kaum einem bestimmten Dosis- oder Fraktionierungsschema, wie z. B. 10-12 Fraktionen mit 4-5 Gy, 5 Fraktionen mit 10 Gy, 3 Fraktionen mit 20-22 Gy und 1 Fraktion mit 15-30 Gy zuordnen, da multiple patientenspezifische, konkurrierende Risiken dabei einen wesentlichen Einfluss zu haben scheinen. Es wird zukuenftig erforderlich sein, praetherapeutische Patienten- und Tumorcharakteristika genauer zu erfassen, dosimetrische Parameter besser zu

  6. Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients.

    Science.gov (United States)

    Jiang, Lichun; Liang, Xiaofang; Li, Yumei; Wang, Jing; Zaneveld, Jacques Eric; Wang, Hui; Xu, Shan; Wang, Keqing; Wang, Binbin; Chen, Rui; Sui, Ruifang

    2015-09-04

    comprehensive genetic characterization of a large collection of Chinese USH patients. Up to 90 % of USH patients have disease caused by mutations in known USH disease genes. By combining NGS-based molecular diagnosis and patient clinical information, a more accurate diagnosis, prognosis and personalized treatment of USH patients can be achieved.

  7. A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

    Science.gov (United States)

    Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

    2017-12-20

    Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

  8. 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.

  9. 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).

  10. The Effect of Neuro-Linguistic Programming (NLP on Reading Comprehension in English for Specific Purposes Courses

    Directory of Open Access Journals (Sweden)

    Fahimeh Farahani

    2018-01-01

    Full Text Available Neuro-Linguistic Programming (NLP has potential to help language learners; however, it has received scant attention. The present study was an attempt to investigate the effect of NLP techniques on reading comprehension of English as a Foreign Language (EFL learners at an English for Specific Purposes (ESP course. To achieve this goal, two intact classes of students were selected to form an experimental group (n=30 and a control group (n=30. A reading pretest (based on the course content was given to all participants. The sensory learning styles of the participants were diagnosed using Reid's (1987 leaning style questionnaire, and the participants in the experimental group were familiarized with NLP techniques to be able to implement these techniques in their reading. In the control group, the conventional approach to teach ESP reading was used. Considering the analysis of posttest results through ANCOVA, it was found that implementation of NLP techniques can have significant effect on reading comprehension of Iranian undergraduate EFL learners. Pedagogical implications are discussed.

  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. Chronic phase of Chagas disease: why should it be treated? A comprehensive review

    Directory of Open Access Journals (Sweden)

    José Rodrigues Coura

    2011-09-01

    Full Text Available The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii promote tissue regeneration to prevent fibrosis, (iii reverse existing fibrosis, (iv prevent cardiomyopathy, megaoesophagus and megacolon and (v reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.

  14. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

    Directory of Open Access Journals (Sweden)

    Christina M Lill

    Full Text Available More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD. To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8 association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P  =  1.3 × 10(-8. All meta-analysis results are freely available on a dedicated online database (www.pdgene.org, which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

  15. Communicating projected survival with treatments for chronic kidney disease: patient comprehension and perspectives on visual aids.

    Science.gov (United States)

    Dowen, Frances; Sidhu, Karishma; Broadbent, Elizabeth; Pilmore, Helen

    2017-09-21

    Mortality in end stage renal disease (ESRD) is higher than many malignancies. There is no data about the optimal way to present information about projected survival to patients with ESRD. In other areas, graphs have been shown to be more easily understood than narrative. We examined patient comprehension and perspectives on graphs in communicating projected survival in chronic kidney disease (CKD). One hundred seventy-seven patients with CKD were shown 4 different graphs presenting post transplantation survival data. Patients were asked to interpret a Kaplan Meier curve, pie chart, histogram and pictograph and answer a multi-choice question to determine understanding. We measured interpretation, usefulness and preference for the graphs. Most patients correctly interpreted the graphs. There was asignificant difference in the percentage of correct answers when comparing different graph types (p = 0.0439). The pictograph was correctly interpreted by 81% of participants, the histogram by 79%, pie chart by 77% and Kaplan Meier by 69%. Correct interpretation of the histogram was associated with educational level (p = 0.008) and inversely associated with age > 65 (p = 0.008). Of those who interpreted all four graphs correctly, there was an association with employment (p = 0.001) and New Zealand European ethnicity (p = 0.002). 87% of patients found the graphs useful. The pie chart was the most preferred graph (p 0.002). The readability of the graphs may have been improved with an alternative colour choice, especially in the setting of visual impairment. Visual aids, can be beneficial adjuncts to discussing survival in CKD.

  16. [Effect of comprehensive control and prevention for chronic disease in demonstration plot of Chongqing].

    Science.gov (United States)

    Qi, Li; Ding, Xian-bin; Mao, De-qiang; Feng, Lian-gui; Wang, Yu-lin; Jiao, Yan; Zhang, Chun-hua; Lü, Xiao-yan; Li, Hong; Xia, Yi-yin

    2013-03-01

    To evaluate the effect of comprehensive control and prevention for chronic diseases in demonstration plot of Chongqing. Residents were enrolled through multi-stage stratified random sampling method from 17 districts or counties which had successfully established demonstration plots and 21 districts or counties which had not established demonstration plots (non-demonstration plot for short) yet on May, 2012. Questionnaire was designed to survey awareness of health knowledge, health behaviors and utilization of health supportive tools. The results were analyzed by SPSS 15.0 software. We investigated 15 108 residents, 6156 of which were in demonstration plot and others (8951) were not. The findings revealed the percentage of the people who were aware the national action of health lifestyle in demonstration plot and in non-demonstration plot were 44.4% (2734/6157) and 40.2% (3598/8951), respectively, and the awareness of the hypertension risk of too much sodium were 72.4% (4458/6156) and 67.5% (6042/8951), respectively, and the awareness of the cardinal vascular disease (CVD) risk of obesity and overweight were 77.2% (4753/6157) and 69.6% (6230/8951), respectively. About the residents' health behaviors in demonstration plot and in non-demonstration plot, the utilization rates of salt restriction scoop or pot were 23.5% (1447/6157) and 17.9% (1602/8951), and the utilization rates of oil restriction pot were 16.7% (1028/6157) and 11.8% (1064/8951), respectively. Totally, 33 of the 37 indexes were shown higher in demonstration plot than that in non-demonstration plot (P plot was more effective, and the remarkable improvement of health knowledge and behaviors level had been achieved in demonstration plot.

  17. Addressing non-communicable diseases in the Seychelles: towards a comprehensive plan of action.

    Science.gov (United States)

    Bovet, Pascal; Viswanathan, Bharathi; Shamlaye, Conrad; Romain, Sarah; Gedeon, Jude

    2010-06-01

    This article reviews the different steps taken during the past 20 years for the prevention and control of non-communicable diseases (NCDs) in the Seychelles. National surveys revealed high levels of several cardiovascular risk factors and prompted an organized response, starting with the creation of an NCD unit in the Ministry of Health. Information campaigns and nationwide activities raised awareness and rallied increasingly broad and high-level support. Significant policy was developed including comprehensive tobacco legislation and a School Nutrition Policy that bans soft drinks in schools. NCD guidelines were developed and specialized 'NCD nurses' were trained to complement doctors in district health centers. Decreasing smoking prevalence is evidence of success, but the raising so-called diabesity epidemic calls for an integrated multi-sector policy to mould an environment conducive to healthy behaviors. Essential components of these efforts include: effective surveillance mechanisms supplemented by focused research; generating broad interest and consensus; mobilizing leadership and commitment at all levels; involving local and international expertise; building on existing efforts; and seeking integrated, multi-disciplinary and multi-sector approaches.

  18. Use of the Menopause-Specific Quality of Life (MENQOL) questionnaire in research and clinical practice: a comprehensive scoping review.

    Science.gov (United States)

    Sydora, Beate C; Fast, Hilary; Campbell, Sandy; Yuksel, Nese; Lewis, Jacqueline E; Ross, Sue

    2016-09-01

    The Menopause-Specific Quality of Life (MENQOL) questionnaire was developed as a validated research tool to measure condition-specific QOL in early postmenopausal women. We conducted a comprehensive scoping review to explore the extent of MENQOL's use in research and clinical practice to assess its value in providing effective, adequate, and comparable participant assessment information. Thirteen biomedical and clinical databases were systematically searched with "menqol" as a search term to find articles using MENQOL or its validated derivative MENQOL-Intervention as investigative or clinical tools from 1996 to November 2014 inclusive. Review articles, conference abstracts, proceedings, dissertations, and incomplete trials were excluded. Additional articles were collected from references within key articles. Three independent reviewers extracted data reflecting study design, intervention, sample characteristics, MENQOL questionnaire version, modifications and language, recall period, and analysis detail. Data analyses included categorization and descriptive statistics. The review included 220 eligible papers of various study designs, covering 39 countries worldwide and using MENQOL translated into more than 25 languages. A variety of modifications to the original questionnaire were identified, including omission or addition of items and alterations to the validated methodological analysis. No papers were found that described MENQOL's use in clinical practice. Our study found an extensive and steadily increasing use of MENQOL in clinical and epidemiological research over 18 years postpublication. Our results stress the importance of proper reporting and validation of translations and variations to ensure outcome comparison and transparency of MENQOL's use. The value of MENQOL in clinical practice remains unknown.

  19. Toward comprehensive detection of sight threatening retinal disease using a multiscale AM-FM methodology

    Science.gov (United States)

    Agurto, C.; Barriga, S.; Murray, V.; Murillo, S.; Zamora, G.; Bauman, W.; Pattichis, M.; Soliz, P.

    2011-03-01

    In the United States and most of the western world, the leading causes of vision impairment and blindness are age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. In the last decade, research in automatic detection of retinal lesions associated with eye diseases has produced several automatic systems for detection and screening of AMD, DR, and glaucoma. However. advanced, sight-threatening stages of DR and AMD can present with lesions not commonly addressed by current approaches to automatic screening. In this paper we present an automatic eye screening system based on multiscale Amplitude Modulation-Frequency Modulation (AM-FM) decompositions that addresses not only the early stages, but also advanced stages of retinal and optic nerve disease. Ten different experiments were performed in which abnormal features such as neovascularization, drusen, exudates, pigmentation abnormalities, geographic atrophy (GA), and glaucoma were classified. The algorithm achieved an accuracy detection range of [0.77 to 0.98] area under the ROC curve for a set of 810 images. When set to a specificity value of 0.60, the sensitivity of the algorithm to the detection of abnormal features ranged between 0.88 and 1.00. Our system demonstrates that, given an appropriate training set, it is possible to use a unique algorithm to detect a broad range of eye diseases.

  20. Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection

    Directory of Open Access Journals (Sweden)

    Abeer E. Mustafa

    2018-05-01

    Full Text Available Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a result, these technologies have become a valuable tool for gene discovery and for clinical diagnostics. The AmpliSeq Inherited Disease Panel (IDP consists of 328 genes underlying more than 700 inherited diseases. Here, we aimed to assess the performance of the IDP as a sensitive and rapid comprehensive gene panel testing. A total of 88 patients with inherited diseases and causal mutations that were previously identified by Sanger sequencing were randomly selected for assessing the performance of the IDP. The IDP successfully detected 93.1% of the mutations in our validation cohort, achieving high overall gene coverage (98%. The sensitivity for detecting single nucleotide variants (SNVs and short Indels was 97.3% and 69.2%, respectively. IDP, when coupled with Ion Torrent Personal Genome Machine (PGM, delivers comprehensive and rapid sequencing for genes that are responsible for various inherited diseases. Our validation results suggest the suitability of this panel for use as a first-line screening test after applying the necessary clinical validation.

  1. Design of comprehensive Alzheimer's disease centers to address unmet national needs.

    Science.gov (United States)

    Trojanowski, John Q; Arnold, Steven E; Karlawish, Jason H; Brunden, Kurt; Cary, Mark; Davatzikos, Christos; Detre, John; Gaulton, Glen; Grossman, Murray; Hurtig, Howard; Jedrziewski, Kathryn; McCluskey, Leo; Naylor, Mary; Polsky, Daniel; Schellenberg, Gerard D; Siderowf, Andrew; Shaw, Leslie M; Van Deerlin, Vivianna; Wang, Li-San; Werner, Rachel; Xie, Sharon X; Lee, Virginia M-Y

    2010-03-01

    The problem of Alzheimer's disease (AD) exemplifies the challenges of dealing with a broad range of aging-related chronic disorders that require long-term, labor-intensive, and expensive care. As the baby boom generation ages and brain diseases become more prevalent, the need to confront the pending health care crisis is more urgent than ever before. Indeed, there is now a critical need to expand significantly the national effort to solve the problem of AD, with special focus on prevention. The Campaign to Prevent Alzheimer's Disease by 2020 (PAD2020) aims to create a new paradigm for planning and supporting the organization of worldwide cooperative research networks to develop new technologies for early detection and treatments of aging-related memory and motor impairments. PAD 2020 is developing an implementation plan to justify (1) increasing the federal budget for research, (2) developing novel national resources to discover new interventions for memory and motor disorders, and (3) creating innovative and streamlined decision-making processes for selecting and supporting new ideas. Since 1978 the National Institute on Aging or National Institute of Health (NIH) established an extensive national network of AD research facilities at academic institutions including AD Centers (ADCs), Consortium to Establish a Registry for AD, AD Cooperative Study (ADCS), AD Drug Discovery Program, National Alzheimer's Coordinating Center, National Cell Repository for AD, and AD Neuroimaging Initiative. However, despite the success of these programs and their critical contributions, they are no longer adequate to meet the challenges presented by AD. PAD 2020 is designed to address these changes by improving the efficiency and effectiveness of these programs. For example, the ADCs (P30s and P50s) can be enhanced by converting some into Comprehensive Alzheimer's Disease Centers (CADCs) to support not only research, but also by being demonstration projects on care/treatment, clinical

  2. 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).

  3. 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

  4. Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

    Science.gov (United States)

    Joubert, Sven; Vallet, Guillaume T; Montembeault, Maxime; Boukadi, Mariem; Wilson, Maximiliano A; Laforce, Robert Jr; Rouleau, Isabelle; Brambati, Simona M

    2017-07-01

    The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016 : a systematic analysis for the Global Burden of Disease Study 2016

    NARCIS (Netherlands)

    Hoek, H. W.; van Boven, Job; Postma, Maarten

    2017-01-01

    BACKGROUND: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations

  6. Salivary Gland Pathology in IgG4-Related Disease: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Ilaria Puxeddu

    2018-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a rare fibroinflammatory condition that can affect almost any organ, characterized by swollen lesions and often by eosinophilia and elevated serum IgG4 concentrations. The diagnosis of IgG4-RD is a challenging task: in fact, single or multiple organs can be affected and clinical, serological, and histological findings can be heterogeneous. In IgG4-RD, the involvement of salivary glands is observed in 27% to 53% of patients. Several organ-specific conditions, now recognized as different manifestations of IgG4-related sialadenitis (IgG4-RS, were viewed in the past as individual disease entities. The study of salivary glands may sometimes be complex, because of the number of pathological conditions that may affect them, often with overlapping clinical pictures. Integration of different imaging techniques is often required in the case of swelling of salivary glands, even though biopsy remains the gold standard for a definite diagnosis of IgG4-RS. Thus, in this review, we discuss new insights in the pathogenesis of IgG4-RD, focusing on its clinical aspects and the tools that are currently available for a correct differential diagnosis when the salivary glands are involved.

  7. PRGdb 3.0: a comprehensive platform for prediction and analysis of plant disease resistance genes.

    Science.gov (United States)

    Osuna-Cruz, Cristina M; Paytuvi-Gallart, Andreu; Di Donato, Antimo; Sundesha, Vicky; Andolfo, Giuseppe; Aiese Cigliano, Riccardo; Sanseverino, Walter; Ercolano, Maria R

    2018-01-04

    The Plant Resistance Genes database (PRGdb; http://prgdb.org) has been redesigned with a new user interface, new sections, new tools and new data for genetic improvement, allowing easy access not only to the plant science research community but also to breeders who want to improve plant disease resistance. The home page offers an overview of easy-to-read search boxes that streamline data queries and directly show plant species for which data from candidate or cloned genes have been collected. Bulk data files and curated resistance gene annotations are made available for each plant species hosted. The new Gene Model view offers detailed information on each cloned resistance gene structure to highlight shared attributes with other genes. PRGdb 3.0 offers 153 reference resistance genes and 177 072 annotated candidate Pathogen Receptor Genes (PRGs). Compared to the previous release, the number of putative genes has been increased from 106 to 177 K from 76 sequenced Viridiplantae and algae genomes. The DRAGO 2 tool, which automatically annotates and predicts (PRGs) from DNA and amino acid with high accuracy and sensitivity, has been added. BLAST search has been implemented to offer users the opportunity to annotate and compare their own sequences. The improved section on plant diseases displays useful information linked to genes and genomes to connect complementary data and better address specific needs. Through, a revised and enlarged collection of data, the development of new tools and a renewed portal, PRGdb 3.0 engages the plant science community in developing a consensus plan to improve knowledge and strategies to fight diseases that afflict main crops and other plants. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. 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

  9. The Relationship between Listening Comprehension of Text and Sentences in Preschoolers: Specific or Mediated by Lower and Higher Level Components?

    Science.gov (United States)

    Florit, Elena; Roch, Maja; Levorato, M. Chiara

    2013-01-01

    Two studies explored the relation between listening comprehension of text and listening comprehension of sentences in preschoolers aged 4 to 5 years, 11 months. The first study analyzed this relationship taking into account the role of lower level components, namely, word knowledge and verbal working memory, as possible mediators. These components…

  10. How working memory relates to children's reading comprehension: The importance of domain-specificity in storage and processing

    NARCIS (Netherlands)

    Nouwens, S.; Groen, M.A.; Verhoeven, L.T.W.

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the

  11. Effects of reciprocal teaching on reading comprehension of low-achieving adolescents. The importance of specific teacher skills

    NARCIS (Netherlands)

    M. Okkinga; Dr. A.J.S. van Gelderen; R. van Steensel

    2016-01-01

    Low-achieving adolescents are known to have difficulties with reading comprehension. This article discusses how reciprocal teaching can improve low-achieving adolescents' reading comprehension in whole-classroom settings (as opposed to small-group settings) and to what extent intervention effects

  12. Effects of reciprocal teaching on reading comprehension of low-achieving adolescents. The importance of specific teacher skills

    NARCIS (Netherlands)

    Okkinga, Mariska; van Steensel, Roel; van Gelderen, Amos J.S.; Sleegers, Peter J.C.

    2018-01-01

    Low-achieving adolescents are known to have difficulties with reading comprehension. This article discusses how reciprocal teaching can improve low-achieving adolescents' reading comprehension in whole-classroom settings (as opposed to small-group settings) and to what extent intervention effects

  13. How Working Memory Relates to Children's Reading Comprehension: The Importance of Domain-Specificity in Storage and Processing

    Science.gov (United States)

    Nouwens, Suzan; Groen, Margriet A.; Verhoeven, Ludo

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the current study, we investigated the contribution of…

  14. Effects of Reciprocal Teaching on Reading Comprehension of Low-Achieving Adolescents. The Importance of Specific Teacher Skills

    Science.gov (United States)

    Okkinga, Mariska; van Steensel, Roel; van Gelderen, Amos J. S.; Sleegers, Peter J. C.

    2018-01-01

    Low-achieving adolescents are known to have difficulties with reading comprehension. This article discusses how reciprocal teaching can improve low-achieving adolescents' reading comprehension in whole-classroom settings (as opposed to small-group settings) and to what extent intervention effects are dependent on teacher behaviour. Over the course…

  15. 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...

  16. 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...

  17. 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.

  18. Microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease: A comprehensive meta-analysis

    OpenAIRE

    LI, HUI; FU, WEI-PING; HONG, ZE-HUI

    2012-01-01

    Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the detoxification the products of smoking and is proposed to be a genetic factor for the development of chronic obstructive pulmonary disease (COPD). Two functional polymorphisms of EPHX1, T113C and A139G, have been analyzed in numerous studies to assess the COPD risk attributed to these variants. However, the conclusions were controversial. We performed a comprehensive meta-analysis to clarify these findings. A total of 24 studie...

  19. 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.

  20. 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...

  1. [Study on the effectiveness of implementation: the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

    Science.gov (United States)

    Zhang, J; Jin, R R; Li, J J; Li, J L; Su, X W; Deng, G J; Ma, S; Zhao, J; Wang, Y P; Bian, F; Qu, Y M; Shen, Z Z; Jiang, Y; Liu, Y L

    2018-04-10

    Objective: To assess the implementation and impact of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: Both sociological and epidemiological methods were used to collect qualitative and quantitative data in November and December, 2016 in order to conduct on process and outcome evaluation of the above mentioned objective. In the meantime, case study was also conducted. Results: All the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were found well implemented across the country, with health education and health promotion, surveillance and safeguard measures in particular. A government-led and inter-sector coordination and communication mechanism had been well established, with more than 16 non-health departments actively involved. 28.7% of the residents living in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were aware of the key messages related to chronic diseases. Among the residents, 72.1% of them consumed vegetables and 53.6% consumed fruits daily, with another 86.9% walked at least 10 minutes per day. Over 70% of the patients with hypertension or diabetes reported that they were taken care of by the Community Health Centers, and above 50% of them were under standardized management. Residents, living in the National Demonstration Areas under higher ranking of implementation scores, were more likely to be aware of relevant knowledge on chronic disease control and prevention ( OR =6.591, 95% CI : 5.188-8.373), salt reduction ( OR =1.352, 95% CI : 1.151-1.589), oil reduction ( OR =1.477, 95% CI : 1.249-1.746) and recommendation on physical activities ( OR =1.975, 95% CI : 1.623- 2.403). Conclusion: The implementation of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases had served a local

  2. Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity – A Comprehensive Review

    Science.gov (United States)

    Mozaffarian, Dariush

    2015-01-01

    Suboptimal nutrition is a leading cause of poor health. Nutrition and policy science have advanced rapidly, creating confusion yet also providing powerful opportunities to reduce the adverse health and economic impacts of poor diets. This review considers the history, new evidence, controversies, and corresponding lessons for modern dietary and policy priorities for cardiovascular diseases, obesity, and diabetes. Major identified themes include the importance of evaluating the full diversity of diet-related risk pathways, not just obesity and blood lipids; focusing on foods and overall diet patterns, rather than single isolated nutrients; recognizing the complex influences of different foods on long-term weight regulation, rather than simply counting calories; and characterizing and implementing evidence-based strategies, including policy approaches, for lifestyle change. Evidence-informed dietary priorities include increased fruits, nonstarchy vegetables, nuts, legumes, fish, vegetable oils, yogurt, and minimally processed whole grains; and fewer red meats, processed (e.g., sodium-preserved) meats, and foods rich in refined grains, starch, added sugars, salt, and trans fat. More investigation is needed on cardiometabolic effects of phenolics, dairy fat, probiotics, fermentation, coffee, tea, cocoa, eggs, specific vegetable and tropical oils, vitamin D, individual fatty acids, and diet-microbiome interactions. Little evidence to-date supports cardiometabolic relevance of other popular priorities: e.g., local, organic, grass-fed, farmed/wild, non-GMO. Evidence-based personalized nutrition appears to depend more on non-genetic characteristics (e.g., physical activity, abdominal adiposity, gender, socioeconomic status, culture) than genetic factors. Food choices must be strongly supported by clinical behavior change efforts, health systems reforms, novel technologies, and robust policy strategies, including those targeting economic incentives, schools and workplaces

  3. Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review.

    Science.gov (United States)

    Mozaffarian, Dariush

    2016-01-12

    Suboptimal nutrition is a leading cause of poor health. Nutrition and policy science have advanced rapidly, creating confusion yet also providing powerful opportunities to reduce the adverse health and economic impacts of poor diets. This review considers the history, new evidence, controversies, and corresponding lessons for modern dietary and policy priorities for cardiovascular diseases, obesity, and diabetes mellitus. Major identified themes include the importance of evaluating the full diversity of diet-related risk pathways, not only blood lipids or obesity; focusing on foods and overall diet patterns, rather than single isolated nutrients; recognizing the complex influences of different foods on long-term weight regulation, rather than simply counting calories; and characterizing and implementing evidence-based strategies, including policy approaches, for lifestyle change. Evidence-informed dietary priorities include increased fruits, nonstarchy vegetables, nuts, legumes, fish, vegetable oils, yogurt, and minimally processed whole grains; and fewer red meats, processed (eg, sodium-preserved) meats, and foods rich in refined grains, starch, added sugars, salt, and trans fat. More investigation is needed on the cardiometabolic effects of phenolics, dairy fat, probiotics, fermentation, coffee, tea, cocoa, eggs, specific vegetable and tropical oils, vitamin D, individual fatty acids, and diet-microbiome interactions. Little evidence to date supports the cardiometabolic relevance of other popular priorities: eg, local, organic, grass-fed, farmed/wild, or non-genetically modified. Evidence-based personalized nutrition appears to depend more on nongenetic characteristics (eg, physical activity, abdominal adiposity, gender, socioeconomic status, culture) than genetic factors. Food choices must be strongly supported by clinical behavior change efforts, health systems reforms, novel technologies, and robust policy strategies targeting economic incentives, schools and

  4. 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...

  5. 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

  6. DincRNA: a comprehensive web-based bioinformatics toolkit for exploring disease associations and ncRNA function.

    Science.gov (United States)

    Cheng, Liang; Hu, Yang; Sun, Jie; Zhou, Meng; Jiang, Qinghua

    2018-06-01

    DincRNA aims to provide a comprehensive web-based bioinformatics toolkit to elucidate the entangled relationships among diseases and non-coding RNAs (ncRNAs) from the perspective of disease similarity. The quantitative way to illustrate relationships of pair-wise diseases always depends on their molecular mechanisms, and structures of the directed acyclic graph of Disease Ontology (DO). Corresponding methods for calculating similarity of pair-wise diseases involve Resnik's, Lin's, Wang's, PSB and SemFunSim methods. Recently, disease similarity was validated suitable for calculating functional similarities of ncRNAs and prioritizing ncRNA-disease pairs, and it has been widely applied for predicting the ncRNA function due to the limited biological knowledge from wet lab experiments of these RNAs. For this purpose, a large number of algorithms and priori knowledge need to be integrated. e.g. 'pair-wise best, pairs-average' (PBPA) and 'pair-wise all, pairs-maximum' (PAPM) methods for calculating functional similarities of ncRNAs, and random walk with restart (RWR) method for prioritizing ncRNA-disease pairs. To facilitate the exploration of disease associations and ncRNA function, DincRNA implemented all of the above eight algorithms based on DO and disease-related genes. Currently, it provides the function to query disease similarity scores, miRNA and lncRNA functional similarity scores, and the prioritization scores of lncRNA-disease and miRNA-disease pairs. http://bio-annotation.cn:18080/DincRNAClient/. biofomeng@hotmail.com or qhjiang@hit.edu.cn. Supplementary data are available at Bioinformatics online.

  7. 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.

  8. 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.

  9. Mapping the brain's orchestration during speech comprehension: task-specific facilitation of regional synchrony in neural networks

    Directory of Open Access Journals (Sweden)

    Keil Andreas

    2004-10-01

    Full Text Available Abstract Background How does the brain convert sounds and phonemes into comprehensible speech? In the present magnetoencephalographic study we examined the hypothesis that the coherence of electromagnetic oscillatory activity within and across brain areas indicates neurophysiological processes linked to speech comprehension. Results Amplitude-modulated (sinusoidal 41.5 Hz auditory verbal and nonverbal stimuli served to drive steady-state oscillations in neural networks involved in speech comprehension. Stimuli were presented to 12 subjects in the following conditions (a an incomprehensible string of words, (b the same string of words after being introduced as a comprehensible sentence by proper articulation, and (c nonverbal stimulations that included a 600-Hz tone, a scale, and a melody. Coherence, defined as correlated activation of magnetic steady state fields across brain areas and measured as simultaneous activation of current dipoles in source space (Minimum-Norm-Estimates, increased within left- temporal-posterior areas when the sound string was perceived as a comprehensible sentence. Intra-hemispheric coherence was larger within the left than the right hemisphere for the sentence (condition (b relative to all other conditions, and tended to be larger within the right than the left hemisphere for nonverbal stimuli (condition (c, tone and melody relative to the other conditions, leading to a more pronounced hemispheric asymmetry for nonverbal than verbal material. Conclusions We conclude that coherent neuronal network activity may index encoding of verbal information on the sentence level and can be used as a tool to investigate auditory speech comprehension.

  10. Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

    Science.gov (United States)

    2017-10-01

    including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations...2% Movember-Prostate Cancer Foundation $250,000/yr Challenge Award Interrogating DNA Repair Defects to Improve Management...Improve Treatment for Advanced Prostate Cancer Goal(s): Comprehensively interrogate DNA repair alterations in both AR-positive and AR-negative CRPC

  11. Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

    Science.gov (United States)

    Hassan, Kareem; Bhalla, Varun; Ezz El Regal, Mohammed; A-Kader, H Hesham

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD. PMID:25232245

  12. 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

  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. 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

  15. 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

  16. Liver enzymes serum levels in patients with chronic kidney disease on hemodialysis: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Luís Henrique Bezerra Cavalcanti Sette

    2014-04-01

    Full Text Available We reviewed the literature regarding the serum levels of the enzymes aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase in patients with chronic kidney disease on hemodialysis with and without viral hepatitis. Original articles published up to January 2013 on adult patients with chronic kidney disease on hemodialysis were selected. These articles contained the words “transaminases” “aspartate aminotransferase” “alanine aminotransferase” “gamma glutamyl transferase,” “liver enzymes”, AND “dialysis” OR “hemodialysis”. A total of 823 articles were retrieved. After applying the inclusion and exclusion criteria, 49 articles were selected. The patients with chronic kidney disease on hemodialysis had reduced serum levels of aminotransferases due to hemodilution, lower pyridoxine levels, or elevated homocysteine levels. The chronic kidney disease patients on hemodialysis infected with the hepatitis C virus also had lower aminotransferase levels compared with the infected patients without chronic kidney disease. This reduction is in part due to decreased viremia caused by the dialysis method, the production of a hepatocyte growth factor and endogenous interferon-α, and lymphocyte activation, which decreases viral action on hepatocytes. Few studies were retrieved on gamma-glutamyl transferase serum levels; those found reported that there were no differences between the patients with or without chronic kidney disease. The serum aminotransferase levels were lower in the patients with chronic kidney disease on hemodialysis (with or without viral hepatitis than in the patients with normal renal function; this reduction has a multifactorial origin.

  17. Infectious Disease in the Twenty-First Century: The Need for a Comprehensive Strategy

    National Research Council Canada - National Science Library

    Mason, Peter W

    1999-01-01

    .... Despite the dramatic advances in genetics and biotechnology that occurred over the course of this decade, humanity has seen the nature and scope of the infectious disease threat evolve in ways...

  18. Role of strain imaging in right heart disease: a comprehensive review.

    Science.gov (United States)

    Kannan, Arun; Poongkunran, Chithra; Jayaraj, Mahendran; Janardhanan, Rajesh

    2014-10-01

    Advances in the imaging techniques of the heart have fueled the interest in understanding of right heart pathology. Recently, speckle tracking echocardiography has shown to aid in understanding various right heart diseases and better management. Its role is well established in diagnosing right heart failure, pulmonary artery hypertension, arrhythmogenic right ventricular dysplasia and congenital heart disease. We review the basic mechanics of speckle tracking and analyze its role in various right heart conditions.

  19. 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.

  20. Immunoglobulin G4 -related kidney disease: A comprehensive pictorial review of the imaging spectrum, Mimickers, and clinicopathological characteristics

    International Nuclear Information System (INIS)

    Seo, Ni Eun; Kim, Jin Hee; Byun, Jae Ho; Lee, Seung Soo; Kim, Hyoung Jung; Lee, Moon Gyu

    2015-01-01

    Immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) has recently been demonstrated to be an important part of IgG4-related sclerosing disease (IgG4-SD). However, since IgG4-KD is still relatively unfamiliar to radiologists and physicians as compared to IgG4-SD involving other organs, it could, therefore, be easily missed. In this article, we present a comprehensive pictorial review of IgG4-KD with regards to the imaging spectrum, mimickers, and clinicopathologic characteristics, based on our clinical experience with 48 patients during the past 13 years, as well as a literature review. Awareness of the broad imaging spectrum of IgG4-KD and differential diagnosis from its mimickers will thus facilitate its early diagnosis and treatment

  1. Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada.

    Science.gov (United States)

    1995-07-01

    To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. Hospital care, home care, single-provider care and multidisciplinary care. Morbidity and quality of life associated with bleeding and treatment. Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. Minimizing morbidity and maximizing functional status and quality of life were given a high value. The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and counselling needs of patients, family members and health care providers. Eligible patients should

  2. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Rivera, A; White, K; Stöhr, H; Steiner, K; Hemmrich, N; Grimm, T; Jurklies, B; Lorenz, B; Scholl, H P; Apfelstedt-Sylla, E; Weber, B H

    2000-10-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.

  3. An eHealth Project on Invasive Pneumococcal Disease: Comprehensive Evaluation of a Promotional Campaign

    Science.gov (United States)

    Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Carozzo, Stefano; Signori, Alessio; Bechini, Angela; Boccalini, Sara

    2016-01-01

    Background The recently launched Pneumo Rischio eHealth project, which consists of an app, a website, and social networking activity, is aimed at increasing public awareness of invasive pneumococcal disease (IPD). The launch of this project was prompted by the inadequate awareness of IPD among both laypeople and health care workers, the heavy socioeconomic burden of IPD, and the far from optimal vaccination coverage in Italy, despite the availability of safe and effective vaccines. Objective The objectives of our study were to analyze trends in Pneumo Rischio usage before and after a promotional campaign, to characterize its end users, and to assess its user-rated quality. Methods At 7 months after launching Pneumo Rischio, we established a 4-month marketing campaign to promote the project. This intervention used various approaches and channels, including both traditional and digital marketing strategies. To highlight usage trends, we used different techniques of time series analysis and modeling, including a modified Mann-Kendall test, change-point detection, and segmented negative binomial regression of interrupted time series. Users were characterized in terms of demographics and IPD risk categories. Customer-rated quality was evaluated by means of a standardized tool in a sample of app users. Results Over 1 year, the app was accessed by 9295 users and the website was accessed by 143,993 users, while the project’s Facebook page had 1216 fans. The promotional intervention was highly effective in increasing the daily number of users. In particular, the Mann-Kendall trend test revealed a significant (P ≤.01) increasing trend in both app and website users, while change-point detection analysis showed that the first significant change corresponded to the start of the promotional campaign. Regression analysis showed a significant immediate effect of the intervention, with a mean increase in daily numbers of users of 1562% (95% CI 456%-4870%) for the app and 620

  4. An eHealth Project on Invasive Pneumococcal Disease: Comprehensive Evaluation of a Promotional Campaign.

    Science.gov (United States)

    Panatto, Donatella; Domnich, Alexander; Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Carozzo, Stefano; Signori, Alessio; Bechini, Angela; Boccalini, Sara

    2016-12-02

    The recently launched Pneumo Rischio eHealth project, which consists of an app, a website, and social networking activity, is aimed at increasing public awareness of invasive pneumococcal disease (IPD). The launch of this project was prompted by the inadequate awareness of IPD among both laypeople and health care workers, the heavy socioeconomic burden of IPD, and the far from optimal vaccination coverage in Italy, despite the availability of safe and effective vaccines. The objectives of our study were to analyze trends in Pneumo Rischio usage before and after a promotional campaign, to characterize its end users, and to assess its user-rated quality. At 7 months after launching Pneumo Rischio, we established a 4-month marketing campaign to promote the project. This intervention used various approaches and channels, including both traditional and digital marketing strategies. To highlight usage trends, we used different techniques of time series analysis and modeling, including a modified Mann-Kendall test, change-point detection, and segmented negative binomial regression of interrupted time series. Users were characterized in terms of demographics and IPD risk categories. Customer-rated quality was evaluated by means of a standardized tool in a sample of app users. Over 1 year, the app was accessed by 9295 users and the website was accessed by 143,993 users, while the project's Facebook page had 1216 fans. The promotional intervention was highly effective in increasing the daily number of users. In particular, the Mann-Kendall trend test revealed a significant (P ≤.01) increasing trend in both app and website users, while change-point detection analysis showed that the first significant change corresponded to the start of the promotional campaign. Regression analysis showed a significant immediate effect of the intervention, with a mean increase in daily numbers of users of 1562% (95% CI 456%-4870%) for the app and 620% (95% CI 176%-1777%) for the website

  5. Behavior, nutrition and lifestyle in a comprehensive health and disease paradigm: skills and knowledge for a predictive, preventive and personalized medicine.

    Science.gov (United States)

    Trovato, Guglielmo M

    2012-03-22

    Health and disease of individuals and of populations are the result of three groups of risk factors: genetics, environment and behavior. Assessment, interventions and tailored changes are possible with integrated approaches more effective if respectful of individuals and different cultures. Assessment tools and integrated interventional strategies are available, but widespread knowledge, skills and competence of well trained individual Medical Doctors still lack. Mediterranean diet is an appropriate reference paradigm because encompasses consistent research background, affordable sustainability, widespread comprehensibility and attractiveness inside a cultural framework of competences and skills in which the Medical Doctors can personally manage the need of prediction (early diagnosis), prevention (intervention on healthy persons) and tailored therapy and follow-up for patients. This profile is flexible and adjustable according to specific needs and preferences due to different economic and ethno-cultural milieus. It can enhanced through on-site/e-learning Continuous Medical Education (CME), by training and using friendly and affordable equipments.

  6. Proceedings of a Sickle Cell Disease Ontology workshop — Towards the first comprehensive ontology for Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Nicola Mulder

    2016-06-01

    The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology.

  7. Disease Management Evaluation: A Comprehensive Review of Current State of the Art.

    Science.gov (United States)

    Conklin, Annalijn; Nolte, Ellen

    2011-01-01

    Many countries across Europe and elsewhere have been experimenting with various structured approaches to manage patients with chronic illness as a way to improve quality of care, reduce costs and lead to better population health outcomes in the long run. Despite a body of studies of disease management interventions, uncertainty about the effects of these remains not least because current guidance on evaluation methods and metrics require further development to enhance scientific rigour while also being practical in routine operations. This article provides details from a report that reviews the academic and grey literature to help advance the task of improving the science of assessing disease management initiatives in Europe. Challenges identified are methodological, analytical and conceptual in nature, with a key issue being the establishment of the counterfactual. An array of sophisticated statistical techniques and analytical frameworks can assist in the construction of a sound comparison strategy when a randomised controlled trial is not possible. Issues to consider include: a clear framework of the mechanisms of action and expected effects of disease management; an understanding of the characteristics of disease management (scope, content, dose, context), and of the intervention and target populations (disease type, severity, case-mix); a period of observation over multiple years; and a logical link between performance measures and the intervention's aims and underlying theory of behaviour change.

  8. Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.

    Directory of Open Access Journals (Sweden)

    Thijs C van Holten

    Full Text Available BACKGROUND: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. METHODS AND FINDINGS: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. CONCLUSIONS: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a

  9. Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states

    Directory of Open Access Journals (Sweden)

    Levitt DG

    2017-07-01

    Full Text Available David G Levitt,1,* Michael D Levitt,2,* 1Department of Integrative Biology and Physiology, University of Minnesota, 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USA *These authors contributed equally to this work Abstract: Protein losing enteropathy (PLE has been associated with more than 60 different conditions, including nearly all gastrointestinal diseases (Crohn’s disease, celiac, Whipple’s, intestinal infections, and so on and a large number of non-gut conditions (cardiac and liver disease, lupus, sarcoidosis, and so on. This review presents the first attempt to quantitatively understand the magnitude of the PLE in relation to the associated pathology for three different disease categories: 1 increased lymphatic pressure (e.g., lymphangiectasis; 2 diseases with mucosal erosions (e.g., Crohn’s disease; and 3 diseases without mucosal erosions (e.g., celiac disease. The PLE with lymphangiectasis results from rupture of the mucosal lymphatics, with retrograde drainage of systemic lymph into the intestinal lumen with the resultant loss of CD4 T cells, which is diagnostic. Mucosal erosion PLE results from macroscopic breakdown of the mucosal barrier, with the epithelial capillaries becoming the rate-limiting factor in albumin loss. The equation derived to describe the relationship between the reduction in serum albumin (CP and PLE indicates that gastrointestinal albumin clearance must increase by at least 17 times normal to reduce the CP by half. The strengths and limitations of the two quantitative measures of PLE (51Cr-albumin or α1-antitrypsin [αAT] clearance are reviewed. αAT provides a simple quantitative diagnostic test that is probably underused clinically. The strong, unexplained correlation between minor decreases in CP and subsequent mortality in seemingly healthy individuals raises the question of whether subclinical PLE could account for the decreased CP and, if so, could the mechanism responsible for

  10. 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

  11. 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

  12. Therapeutic potential of flavonoids in inflammatory bowel disease: A comprehensive review.

    Science.gov (United States)

    Salaritabar, Ali; Darvishi, Behrad; Hadjiakhoondi, Farzaneh; Manayi, Azadeh; Sureda, Antoni; Nabavi, Seyed Fazel; Fitzpatrick, Leo R; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2017-07-28

    The inflammatory process plays a central role in the development and progression of numerous pathological situations, such as inflammatory bowel disease (IBD), autoimmune and neurodegenerative diseases, metabolic syndrome, and cardiovascular disorders. IBDs involve inflammation of the gastrointestinal area and mainly comprise Crohn's disease (CD) and ulcerative colitis (UC). Both pathological situations usually involve recurring or bloody diarrhea, pain, fatigue and weight loss. There is at present no pharmacological cure for CD or UC. However, surgery may be curative for UC patients. The prescribed treatment aims to ameliorate the symptoms and prevent and/or delay new painful episodes. Flavonoid compounds are a large family of hydroxylated polyphenolic molecules abundant in plants, including vegetables and fruits which are the major dietary sources of these compounds for humans, together with wine and tea. Flavonoids are becoming very popular because they have many health-promoting and disease-preventive effects. Most interest has been directed towards the antioxidant activity of flavonoids, evidencing a remarkable free-radical scavenging capacity. However, accumulating evidence suggests that flavonoids have many other biological properties, including anti-inflammatory, antiviral, anticancer, and neuroprotective activities through different mechanisms of action. The present review analyzes the available data about the different types of flavonoids and their potential effectiveness as adjuvant therapy of IBDs.

  13. Traditional Chinese medicines in the management of cardiovascular diseases: a comprehensive systematic review.

    Science.gov (United States)

    Layne, Kerry; Ferro, Albert

    2017-01-01

    The aim was to perform a systematic review of the efficacy of traditional Chinese medicines (TCM) in cardiovascular disease. Electronic databases were searched up to 11 November 2015 for all randomized-controlled trials evaluating the effect of TCM in hypertension, ischaemic stroke, heart failure, coronary heart disease and type 2 diabetes mellitus. Pooled odds ratios (ORs) were calculated using a fixed-effects model. Four hypertension studies were eligible for statistical analysis and included 133 patients receiving TCM and 130 control patients. There were significant reductions in systolic blood pressure in patients receiving TCM, comparable to results achieved with pharmaceutical medicines. An OR of 3.781 (95% confidence interval 2.392, 5.977; P = 0.000) was observed for the anti-hypertensive effect of TCM. Significant heterogeneity was present (P = 0.011), with a tendency towards publication bias that did not reach significance (P = 0.05275). Outcome measures for other cardiovascular diseases were inconsistent. Certain TCM compounds appear to have significant anti-hypertensive effects, and although some are associated in some studies with improved outcomes in coronary heart disease, heart failure and type 2 diabetes mellitus, the data are inconsistent and will require large-scale randomized-controlled trials to allow full evaluation of any potential therapeutic benefit in these areas. © 2016 The British Pharmacological Society.

  14. The natural history of gastro-esophageal reflux disease: a comprehensive review.

    Science.gov (United States)

    Savarino, E; de Bortoli, N; De Cassan, C; Della Coletta, M; Bartolo, O; Furnari, M; Ottonello, A; Marabotto, E; Bodini, G; Savarino, V

    2017-02-01

    Gastroesophageal reflux disease (GERD) is a common disorder of the upper gastrointestinal tract which is typically characterized by heartburn and acid regurgitation. These symptoms are widespread in the community and range from 2.5% to more than 25%. Economic analyses showed an increase in direct and indirect costs related to the diagnosis, treatment and surveillance of GERD and its complications. The aim of this review is to provide current information regarding the natural history of GERD, taking into account the evolution of its definition and the worldwide gradual change of its epidemiology. Present knowledge shows that there are two main forms of GERD, that is erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter comprises the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, which is considered as a pre-cancerous lesion. Although data from medical literature on the natural history of this disease are limited and mainly retrospective, they seem to indicate that both NERD and mild esophagitis tend to remain as such with time and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur in a small proportion of patients, ranging from 0 to 30%, 10 to 22% and 1 to 13% of cases, respectively. It is necessary to stress that these data are strongly influenced by the use of powerful antisecretory drugs (PPIs). Further studies are needed to better elucidate this matter and overcome the present limitations represented by the lack of large prospective longitudinal investigations, absence of homogeneous definitions of the various forms of GERD, influence of different treatments, clear exclusion of patients with functional disorders of the esophagus. © 2016 International Society for Diseases of the Esophagus.

  15. The prospective relationship between work stressors and cardiovascular disease, using a comprehensive work stressor measure for exposure assessment.

    Science.gov (United States)

    Szerencsi, Karolina; van Amelsvoort, Ludovic; Prins, Martin; Kant, Ijmert

    2014-02-01

    The currently used instruments which measure the psychosocial work environment have been criticized. We analyzed the association between work stressors and cardiovascular disease, using the Maastricht Cohort Study Work Stressor Score (MCS-WSS), a comprehensive measure which has been associated with work strain. At baseline 11,489 employees of the Maastricht Cohort Study were participating. This prospective cohort study started in 1998 in the Netherlands and includes a heterogeneous population of employees. The psychosocial work environment, cardiovascular risk factors and the occurrence of cardiovascular disease were measured with questionnaires at various time points during follow-up, the last follow-up was in 2008. For a subsample of employees, CVD extracted from medical records was available. The MCS-WSS consists of items from emotional demands, psychological demands, role clarity, career possibilities, working overtime, job insecurity, cognitive demands, skills discretion and decision authority. Each item has its own contribution in inducing work strain, represented by its own weighting factor. The association between a high exposure to work stressors at baseline and cardiovascular morbidity was assessed with Cox regression analyses. Analyses were adjusted for age, gender, educational level, smoking, body mass index, alcohol consumption and leisure physical activity. During a median follow-up of 49 months, 309 employees developed incident cardiovascular disease. Overall, no significant associations were found between a high exposure to work stressors at baseline and cardiovascular morbidity. The results of this study indicate that high exposure to work stressors has no considerable impact on cardiovascular disease.

  16. COMPREHENSIVE STUDY OF HYDATID DISEASE OF LIVER AND MANAGEMENT AT PERIPHERAL TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Karunaharan Thomas

    2017-04-01

    Full Text Available BACKGROUND Hydatid Disease (HD is a zoonotic disease caused by the larvae of Echinococcosis granulosus, now become a rare clinical entity in teaching medical college hospitals. This is due to the public education about the disease, mode of spread and treatment available. The aim of the study is to review the epidemiology, clinical presentation, diagnostic methods available, organs affected and treatment available in the tertiary hospitals and outcome. MATERIALS AND METHODS Data Collection- Patients with upper right abdominal pain with radiological and ultrasound findings are included in the study. About twenty patients are taken for this study. Medical managements, surgical procedure done and outcomes are recorded, tabulated and analysed. Research Design- Prospective Study, Research Setting- KAPV Govt. Medical College and Mahatma Gandhi Memorial Govt. Hospital, Trichy, Tamilnadu. Duration- 7 yrs. (2009 to 2016 Sample Size- Twenty. Inclusion CriteriaPatients between 12 to 70 years of age of both sexes. Patient having right upper abdomen or epigastric pain with positive radiological and ultrasound findings. Patient willing to participate in the study. Exclusion Criteria- Patients more than 70 years not willing to participate in the study patients absconded in between the management. RESULTS Liver is a commonest solid organ affected by the hydatid disease. Most of the diagnosis are made accidentally when the patients are investigated for some other diseases. The commonest clinical presentation is right abdominal or epigastric pain with hepatomegaly. The average age group is 45 years. X-ray abdomen, ultrasound abdomen are the most useful investigations. Asymptomatic uncomplicated small cyst less than 5 cms are managed with medical treatment. Symptomatic large cysts are submitted for surgical intervention. CONCLUSION The main source of income in majority of rural population is agriculture and sheep and cattle grazing. WHO is working towards the

  17. Vitamin D and its effects on cardiovascular diseases: a comprehensive review.

    Science.gov (United States)

    Pérez-Hernández, Nonanzit; Aptilon-Duque, Gad; Nostroza-Hernández, María Cristina; Vargas-Alarcón, Gilberto; Rodríguez-Pérez, José Manuel; Blachman-Braun, Ruben

    2016-11-01

    Vitamin D is a molecule that is actively involved in multiple metabolic pathways. It is mostly known for its implications related to calcium metabolism. It has also been determined that it actively participates in the cardiovascular system, influencing blood pressure, coronary artery disease and other vascular diseases, such as heart failure and atrial fibrillation. Furthermore, it has been established that this vitamin is extensively involved in the regulation of both the renin angiotensin aldosterone system and the immune system. In this review, we present the different vitamin D metabolic pathways associated with the cardiovascular pathophysiology, and we include studies in animal and human models, as well as some of the controversies found in the literature. This review also incorporates an overview of the implications in the molecular biology and public health fields.

  18. Protective effects of panax notoginseng saponins on cardiovascular diseases: a comprehensive overview of experimental studies.

    Science.gov (United States)

    Yang, Xiaochen; Xiong, Xingjiang; Wang, Heran; Wang, Jie

    2014-01-01

    Panax notoginseng saponins (PNS) are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases.

  19. Protective Effects of Panax Notoginseng Saponins on Cardiovascular Diseases: A Comprehensive Overview of Experimental Studies

    Directory of Open Access Journals (Sweden)

    Xiaochen Yang

    2014-01-01

    Full Text Available Panax notoginseng saponins (PNS are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases.

  20. 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.

  1. 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.

  2. Disease Management Evaluation: A Comprehensive Review of Current State of the Art

    OpenAIRE

    Conklin, Annalijn; Nolte, Ellen

    2011-01-01

    Many countries across Europe and elsewhere have been experimenting with various structured approaches to manage patients with chronic illness as a way to improve quality of care, reduce costs and lead to better population health outcomes in the long run. Despite a body of studies of disease management interventions, uncertainty about the effects of these remains not least because current guidance on evaluation methods and metrics require further development to enhance scientific rigour while ...

  3. 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.

  4. 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.

  5. A comprehensive cooperative project for children with renal diseases in Nicaragua.

    Science.gov (United States)

    Edefonti, A; Marra, G; Castellón Perez, M; Sandoval Díaz, M; Sereni, F

    2010-11-01

    In low-income countries renal diseases generally and chronic kidney disease (CKD) in particular represent a wide-spread and often underdiagnosed clinical problem. The aim of the cooperative project between the pediatric nephrology units of Milan, Italy, and Managua, Nicaragua was to improve the diagnosis and treatment of renal diseases and CKD in Nicaraguan children. When the project started, in 2000, there were many constraints in human and material resources in the Children's Hospital in Managua. Since 2001, a specialized Unit of Pediatric Nephrology and Urology has developed, offering free of charge basic clinical assistance to hospitalized children, and training abroad of the whole staff. Shared protocols, renovation of infrastructure and an information technology (IT) program were implemented. In 2003, renal replacement therapy (RRT) for selected children was initiated, along with a network of six department hospitals in 2005 and, in 2007, a CKD prevention program in the most peripheral Health Units, so that 61% of the Nicaraguan pediatric population is now covered by the project. To ensure implementation of the project, applications for funds to Italian private and public institutions were made and a Nicaraguan charity foundation was activated. The Nicaraguan Ministry of Health and the hospital directors were always involved in the plans of the development of the project and accepted the progressive transfer of the costs to the government, throughout the 9-year duration of the project. The IT program, inclusive of a database of children with kidney and other urinary tract (UT) diseases and a web connection between Milan and Managua, was crucial in monitoring the activities and providing epidemiological data, in order to better allocate resources. The clinical activities and the number of children managed in Managua in 2008 are similar to those of pediatric nephrology units worldwide and depict the level of clinical autonomy achieved. The sister-center model

  6. Comprehensive analysis of the related factors of early hypothyroidism occurring in patients with Graves' disease after 131I treatment

    International Nuclear Information System (INIS)

    Tan Jian; Wang Peng; Zhang Lijuan; He Yajing; Wang Renfei

    2005-01-01

    Objective: To make a comprehensive analysis of the related factors of early hypothyroidism occurring in patients with Graves' disease after 131 I treatment. Methods: The information of 131 I treated Graves' disease was collected including general data, clinical observation, laboratory data, thyroid function test, etc. Then a retrospective statistical analysis was carried out, using cluster analysis, factor analysis, discriminant analysis, multivariate regression analysis, etc. Results: 1) Cluster analysis and factor analysis showed that among clinical observation such as clinical course, treatment course, patients' state and disease occurrance, the first three factors correlated highly; among laboratory data such as thyrotrophin receptor antibody (TRAb), thyroid-stimulating immunoglobulins (TSI), thyroglobulin antibody (TgAb) and thyroid microsomal antibody (TMAb), both the first two and the last two correlated highly, each two factors had the similar effect. 2) Fsher discriminant analysis showed that among the thyroid weight, the effective half life, the maximum 131 I uptake percentage, total dose of 131 I and the average dose of 131 I per gram of thyroid, the last one had the most predicting value for incidence of early hypothyroidism. 3) Logistic regression analysis showed that among all the related factors of early hypothyroidism occurred after 131 I treated Graves' disease, thyroid weight, average dose of 131 I per gram of thyroid, the maximum 131 I uptake percentage and the level of TSI were effective factors. Conclusions: The occurrence of early hypothyroidism for 131 I-treated Graves' disease is probably affected by many factors. If more factors are taken into consideration before therapy and the theraputic dose is well adjusted accordingly, it can reduce the incidence of early hypothroidism to a certain extent. (authors)

  7. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis--A Comprehensive Review and Guide to Therapy. I. Systemic Disease.

    Science.gov (United States)

    Kohanim, Sahar; Palioura, Sotiria; Saeed, Hajirah N; Akpek, Esen K; Amescua, Guillermo; Basu, Sayan; Blomquist, Preston H; Bouchard, Charles S; Dart, John K; Gai, Xiaowu; Gomes, José A P; Gregory, Darren G; Iyer, Geetha; Jacobs, Deborah S; Johnson, Anthony J; Kinoshita, Shigeru; Mantagos, Iason S; Mehta, Jodhbir S; Perez, Victor L; Pflugfelder, Stephen C; Sangwan, Virender S; Sippel, Kimberly C; Sotozono, Chie; Srinivasan, Bhaskar; Tan, Donald T H; Tandon, Radhika; Tseng, Scheffer C G; Ueta, Mayumi; Chodosh, James

    2016-01-01

    The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Demencia en la enfermedad de Alzheimer: un enfoque integral Dementia in Alzheimer's disease: a comprehensive approach

    Directory of Open Access Journals (Sweden)

    Víctor T. Pérez Martínez

    2005-08-01

    Full Text Available El substrato patológico de la principal de las demencias, lo constituyen las siguientes lesiones: la degeneración neurofibrilar abundante y difusa, las placas neuríticas y el depósito anormal de sustancia amiloide en el cerebro, causante de la toxicidad cerebral. La demencia en la enfermedad de Alzheimer cumple con un patrón clínico-topográfico de tipo cortical característico. Su diagnóstico definitivo es anatomopatológico, pero se puede establecer un diagnóstico probable basado en la clínica y en la evaluación neuropsicológica. No existe tratamiento efectivo concluyente para el deterioro cognitivo de la enfermedad de Alzheimer.The pathological substrate of the main dementia is composed of the following lesions: the diffuse and abundant neurofibrillar degeneration, the neuritic plaques and the abnormal deposit of amyloid substance in the brain, causing cerebral toxicity. Dementia in Alzheimer's disease accomplishes a clinicotopographic pattern of characteristic cortical type. Its definitive diagnosis is anatomopathological, but a probable diagnosis based on the clinic and the neuropsychological evaluation can be established. There is no a concluding effective treatment for the cognitive deterioration of Alzheimer's disease.

  9. β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View

    Directory of Open Access Journals (Sweden)

    Botond Penke

    2017-10-01

    Full Text Available Protein dyshomeostasis is the common mechanism of neurodegenerative diseases such as Alzheimer’s disease (AD. Aging is the key risk factor, as the capacity of the proteostasis network declines during aging. Different cellular stress conditions result in the up-regulation of the neurotrophic, neuroprotective amyloid precursor protein (APP. Enzymatic processing of APP may result in formation of toxic Aβ aggregates (β-amyloids. Protein folding is the basis of life and death. Intracellular Aβ affects the function of subcellular organelles by disturbing the endoplasmic reticulum-mitochondria cross-talk and causing severe Ca2+-dysregulation and lipid dyshomeostasis. The extensive and complex network of proteostasis declines during aging and is not able to maintain the balance between production and disposal of proteins. The effectivity of cellular pathways that safeguard cells against proteotoxic stress (molecular chaperones, aggresomes, the ubiquitin-proteasome system, autophagy declines with age. Chronic cerebral hypoperfusion causes dysfunction of the blood-brain barrier (BBB, and thus the Aβ-clearance from brain-to-blood decreases. Microglia-mediated clearance of Aβ also declines, Aβ accumulates in the brain and causes neuroinflammation. Recognition of the above mentioned complex pathogenesis pathway resulted in novel drug targets in AD research.

  10. 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.

  11. Comprehensive analysis of gene-expression profile in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Wei L

    2015-06-01

    Full Text Available Lei Wei,1,* Dong Xu,2,* Yechang Qian,1 Guoyi Huang,1 Wei Ma,1 Fangying Liu,1 Yanhua Shen,1 Zhongfu Wang,1 Li Li,1 Shanfang Zhang,1 Yafang Chen1 1Department of Respiratory Disease, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 2Medical College of Soochow University, Suzhou, People's Republic of China *These authors contributed equally to this work Objective: To investigate the gene-expression profile of chronic obstructive pulmonary disease (COPD patients and explore the possible therapeutic targets. Methods: The microarray raw dataset GSE29133, including three COPD samples and three normal samples, was obtained from Gene Expression Omnibus. After data preprocessing with the Affy package, Student’s t-test was employed to identify the differentially expressed genes (DEGs. The up- and downregulated DEGs were then pooled for gene-ontology and pathway-enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID. The upstream regulatory elements of these DEGs were also explored by using Whole-Genome rVISTA. Furthermore, we constructed a protein–protein interaction (PPI network for DEGs. The surfactant protein D (SP-D serum level and HLA-A gene frequency in COPD patients and healthy controls were also measured by enzyme-linked immunosorbent assay (ELISA and real-time polymerase chain reaction, respectively. Results: A total of 39 up- and 15 downregulated DEGs were screened. Most of the upregulated genes were involved in the immune response process, while the downregulated genes were involved in the steroid metabolic process. Moreover, we also found that HLA-A has the highest degree in the PPI network. The SP-D serum level and HLA-A gene frequency in COPD patients were significantly higher than those in healthy controls (13.62±2.09 ng/mL vs 10.28±2.86 ng/mL; 62.5% vs 12.5%; P<0.05. Conclusion: Our results may help further the understanding of the mechanisms of

  12. Comprehensive SDG goal and targets for non-communicable diseases and mental health.

    Science.gov (United States)

    Minas, Harry; Tsutsumi, Atsuro; Izutsu, Takashi; Goetzke, Kathryn; Thornicroft, Graham

    2015-01-01

    The negotiations on the SDG goals and targets, leading to the sustainable development Declaration in September 2015, are now in the final stages. Ensuring that people with mental disorders are not left behind in the global development program from 2015 to 2030 will require specific and explicit commitments and targets against which progress in mental health can be measured and reported. The arguments for inclusion of explicit mental health targets in the SDGs are compelling. The final negotiations on the SDG goals and targets will now determine whether people with mental illness and psychosocial disabilities will continue to be neglected or will benefit equitably from inclusion in the post-2015 development program.

  13. 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.

  14. 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.

  15. 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…

  16. 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

  17. Erdheim-Chester Disease: Comprehensive Review of Molecular Profiling and Therapeutic Advances.

    Science.gov (United States)

    Haroun, Faysal; Millado, Kristen; Tabbara, Imad

    2017-06-01

    The revised 2016 World Health Organization classification introduced Erdheim-Chester disease (ECD) as a provisional entity within the histiocytic and dendritic cell neoplasms separate from the juvenile xanthogranuloma family based on distinct molecular features. However, evolving knowledge regarding the molecular and genetic aberrations in addition to common clinical features of ECD support the classification of ECD together with Langerhans cell histiocytosis (LCH). Accordingly, ECD can be thought of as an inflammatory myeloid clonal disorder based on the detection of various activating mutations along the mitogen activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) pathway with most notable variant being a valine to a glutamic acid substitution at amino acid 600 in the B-rapidly accelerated fibrosarcoma protein (BRAFV600E). In this group, targeted therapy with a B-Raf inhibitor alone or combined with a MAPK-ERK (MEK) inhibitor has shown promising results based on several case reports. Currently, two phase II trials with BRAF inhibitors are underway and could potentially change the standard of care. MEK inhibitors may also be efficacious in ECD harboring mutations in MAP2K1; other potential targetable aberrations include programed cell death receptor 1 and mutations in phosphoinositide 3-kinase. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Communicating effectiveness of intervention for chronic diseases: what single format can replace comprehensive information?

    Directory of Open Access Journals (Sweden)

    Kristiansen Ivar S

    2008-06-01

    Full Text Available Abstract Background There is uncertainty about how GPs should convey information about treatment effectiveness to their patients in the context of cardiovascular disease. Hence we study the concordance of decisions based on one of four single information formats for treatment effectiveness with subsequent decisions based on all four formats combined with a pictorial representation. Methods A randomized study comprising 1,169 subjects aged 40–59 in Odense, Denmark. Subjects were randomized to receive information in terms of absolute risk reduction (ARR, relative risk reduction (RRR, number needed to treat (NNT, or prolongation of life (POL without heart attack, and were asked whether they would consent to treatment. Subsequently the same information was conveyed with all four formats jointly accompanied by a pictorial presentation of treatment effectiveness. Again, subjects should consider consent to treatment. Results After being informed about all four formats, 52%–79% of the respondents consented to treatment, depending on level of effectiveness and initial information format. Overall, ARR gave highest concordance, 94% (95% confidence interval (91%; 97% between initial and final decision, but ARR was not statistically superior to the other formats. Conclusion Decisions based on ARR had the best concordance with decisions based on all four formats and pictorial representation, but the difference in concordance between the four formats was small, and it is unclear whether respondents fully understood the information they received.

  19. Added sugars drive chronic kidney disease and its consequences: A comprehensive review

    Directory of Open Access Journals (Sweden)

    James J. DiNicolantonio

    2016-06-01

    Full Text Available The consumption of added sugars (e.g. sucrose [table sugar] and high-fructose corn syrup over the last 200 years has increased exponentially and parallels the increased prevalence of chronic kidney disease (CKD. Data for animals and humans suggest that the consumption of added sugars leads to kidney damage and related metabolic derangements that increase cardiovascular risk. Importantly, the consumption of added sugars has been found to induce insulin resistance and increase uric acid in humans, both of which increase the conversion of glucose to fructose (i.e. fructogenesis via the polyol pathway. The polyol pathway has recently been implicated in the contribution and progression of kidney damage, suggesting that even glucose can be toxic to the kidney via its endogenous transformation into fructose in the proximal tubule. Consuming added fructose has been shown to induce insulin resistance, which can lead to hyperglycaemia, oxidative stress, inflammation and the activation of the immune system, all of which can synergistically contribute to kidney damage. CKD guidelines should stress a reduction in the consumption of added sugars as a means to prevent and treat CKD as well as reduce CKD–related morbidity and mortality.

  20. SU-F-T-227: A Comprehensive Patient Specific, Structure Specific, Pre-Treatment 3D QA Protocol for IMRT, SBRT and VMAT - Clinical Experience

    Energy Technology Data Exchange (ETDEWEB)

    Gueorguiev, G; Cotter, C; Young, M; Toomeh, D [Massachusetts General Hospital Boston MA (United States); University of Massachusetts Lowell Lowell, MA (United States); Khan, F; Crawford, B; Turcotte, J; Sharp, G [Massachusetts General Hospital Boston MA (United States); Mah’D, M [University of Massachusetts Lowell Lowell, MA (United States)

    2016-06-15

    Purpose: To present a 3D QA method and clinical results for 550 patients. Methods: Five hundred and fifty patient treatment deliveries (400 IMRT, 75 SBRT and 75 VMAT) from various treatment sites, planned on Raystation treatment planning system (TPS), were measured on three beam-matched Elekta linear accelerators using IBA’s COMPASS system. The difference between TPS computed and delivered dose was evaluated in 3D by applying three statistical parameters to each structure of interest: absolute average dose difference (AADD, 6% allowed difference), absolute dose difference greater than 6% (ADD6, 4% structure volume allowed to fail) and 3D gamma test (3%/3mm DTA, 4% structure volume allowed to fail). If the allowed value was not met for a given structure, manual review was performed. The review consisted of overlaying dose difference or gamma results with the patient CT, scrolling through the slices. For QA to pass, areas of high dose difference or gamma must be small and not on consecutive slices. For AADD to manually pass QA, the average dose difference in cGy must be less than 50cGy. The QA protocol also includes DVH analysis based on QUANTEC and TG-101 recommended dose constraints. Results: Figures 1–3 show the results for the three parameters per treatment modality. Manual review was performed on 67 deliveries (27 IMRT, 22 SBRT and 18 VMAT), for which all passed QA. Results show that statistical parameter AADD may be overly sensitive for structures receiving low dose, especially for the SBRT deliveries (Fig.1). The TPS computed and measured DVH values were in excellent agreement and with minimum difference. Conclusion: Applying DVH analysis and different statistical parameters to any structure of interest, as part of the 3D QA protocol, provides a comprehensive treatment plan evaluation. Author G. Gueorguiev discloses receiving travel and research funding from IBA for unrelated to this project work. Author B. Crawford discloses receiving travel funding from

  1. 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.)

  2. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

    Science.gov (United States)

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-05-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Comprehensive Survey of Domiciliary Triatomine Species Capable of Transmitting Chagas Disease in Southern Ecuador.

    Science.gov (United States)

    Grijalva, Mario J; Villacis, Anita G; Ocaña-Mayorga, Sofia; Yumiseva, Cesar A; Moncayo, Ana L; Baus, Esteban G

    2015-01-01

    Chagas disease is endemic to the southern Andean region of Ecuador, an area with one of the highest poverty rates in the country. However, few studies have looked into the epidemiology, vectors and transmission risks in this region. In this study we describe the triatomine household infestation in Loja province, determine the rate of Trypanosoma cruzi infection in triatomines and study the risk factors associated with infestation. An entomological survey found four triatomine species (Rhodnius ecuadoriensis, Triatoma carrioni, Panstrongylus chinai, and P. rufotuberculatus) infesting domiciles in 68% of the 92 rural communities examined. Nine percent of domiciles were infested, and nymphs were observed in 80% of the infested domiciles. Triatomines were found in all ecological regions below 2,200 masl. We found R. ecuadoriensis (275 to 1948 masl) and T. carrioni (831 to 2242 masl) mostly in bedrooms within the domicile, and they were abundant in chicken coops near the domicile. Established colonies of P. chinai (175 to 2003 masl) and P. rufotuberculatus (404 to 1613 masl) also were found in the domicile. Triatomine infestation was associated with surrogate poverty indicators, such as poor sanitary infrastructure (lack of latrine/toilet [w = 0.95], sewage to environment [w = 1.0]). Vegetation type was a determinant of infestation [w = 1.0] and vector control program insecticide spraying was a protective factor [w = 1.0]. Of the 754 triatomines analyzed, 11% were infected with Trypanosoma cruzi and 2% were infected with T. rangeli. To date, only limited vector control efforts have been implemented. Together with recent reports of widespread sylvatic triatomine infestation and frequent post-intervention reinfestation, these results show that an estimated 100,000 people living in rural areas of southern Ecuador are at high risk for T. cruzi infection. Therefore, there is a need for a systematic, sustained, and monitored vector control intervention that is coupled with

  4. Comprehensive Survey of Domiciliary Triatomine Species Capable of Transmitting Chagas Disease in Southern Ecuador.

    Directory of Open Access Journals (Sweden)

    Mario J Grijalva

    Full Text Available Chagas disease is endemic to the southern Andean region of Ecuador, an area with one of the highest poverty rates in the country. However, few studies have looked into the epidemiology, vectors and transmission risks in this region. In this study we describe the triatomine household infestation in Loja province, determine the rate of Trypanosoma cruzi infection in triatomines and study the risk factors associated with infestation.An entomological survey found four triatomine species (Rhodnius ecuadoriensis, Triatoma carrioni, Panstrongylus chinai, and P. rufotuberculatus infesting domiciles in 68% of the 92 rural communities examined. Nine percent of domiciles were infested, and nymphs were observed in 80% of the infested domiciles. Triatomines were found in all ecological regions below 2,200 masl. We found R. ecuadoriensis (275 to 1948 masl and T. carrioni (831 to 2242 masl mostly in bedrooms within the domicile, and they were abundant in chicken coops near the domicile. Established colonies of P. chinai (175 to 2003 masl and P. rufotuberculatus (404 to 1613 masl also were found in the domicile. Triatomine infestation was associated with surrogate poverty indicators, such as poor sanitary infrastructure (lack of latrine/toilet [w = 0.95], sewage to environment [w = 1.0]. Vegetation type was a determinant of infestation [w = 1.0] and vector control program insecticide spraying was a protective factor [w = 1.0]. Of the 754 triatomines analyzed, 11% were infected with Trypanosoma cruzi and 2% were infected with T. rangeli.To date, only limited vector control efforts have been implemented. Together with recent reports of widespread sylvatic triatomine infestation and frequent post-intervention reinfestation, these results show that an estimated 100,000 people living in rural areas of southern Ecuador are at high risk for T. cruzi infection. Therefore, there is a need for a systematic, sustained, and monitored vector control intervention that is

  5. Comprehensive Survey of Domiciliary Triatomine Species Capable of Transmitting Chagas Disease in Southern Ecuador

    Science.gov (United States)

    Grijalva, Mario J.; Villacis, Anita G.; Ocaña-Mayorga, Sofia; Yumiseva, Cesar A.; Moncayo, Ana L.; Baus, Esteban G.

    2015-01-01

    Background Chagas disease is endemic to the southern Andean region of Ecuador, an area with one of the highest poverty rates in the country. However, few studies have looked into the epidemiology, vectors and transmission risks in this region. In this study we describe the triatomine household infestation in Loja province, determine the rate of Trypanosoma cruzi infection in triatomines and study the risk factors associated with infestation. Methodology/Principal Findings An entomological survey found four triatomine species (Rhodnius ecuadoriensis, Triatoma carrioni, Panstrongylus chinai, and P. rufotuberculatus) infesting domiciles in 68% of the 92 rural communities examined. Nine percent of domiciles were infested, and nymphs were observed in 80% of the infested domiciles. Triatomines were found in all ecological regions below 2,200 masl. We found R. ecuadoriensis (275 to 1948 masl) and T. carrioni (831 to 2242 masl) mostly in bedrooms within the domicile, and they were abundant in chicken coops near the domicile. Established colonies of P. chinai (175 to 2003 masl) and P. rufotuberculatus (404 to 1613 masl) also were found in the domicile. Triatomine infestation was associated with surrogate poverty indicators, such as poor sanitary infrastructure (lack of latrine/toilet [w = 0.95], sewage to environment [w = 1.0]). Vegetation type was a determinant of infestation [w = 1.0] and vector control program insecticide spraying was a protective factor [w = 1.0]. Of the 754 triatomines analyzed, 11% were infected with Trypanosoma cruzi and 2% were infected with T. rangeli. Conclusions/Significance To date, only limited vector control efforts have been implemented. Together with recent reports of widespread sylvatic triatomine infestation and frequent post-intervention reinfestation, these results show that an estimated 100,000 people living in rural areas of southern Ecuador are at high risk for T. cruzi infection. Therefore, there is a need for a systematic, sustained

  6. Effect of a comprehensive plan for periodontal disease care on oral health-related quality of life in patients with periodontal disease in Taiwan.

    Science.gov (United States)

    Wang, Tze-Fang; Fang, Chun-Han; Hsiao, Kai-Jong; Chou, Chyuan

    2018-02-01

    A comprehensive plan for periodontal disease (PD) care in Taiwan provides non-surgical and supportive periodontal treatment. The aim of this study was to determine whether the care plan could improve the oral health-related quality of life of patients with PD.This study was conducted by purposive sampling and a quasi-experimental design. Patients with PD were assigned to either comprehensive periodontal treatment (n = 32) or a simple cleaning regimen (n = 32). Their oral health-related quality of life (OHRQoL) was measured using the Taiwanese version of the Brief World Health Organization Quality of Life (WHOQOL-BREF) scale (general QoL) and the Oral Health Impact Profile (OHIP-14) (OHRQoL). Both scales were completed 14, 28, and 90 days after the initial assessment. The extent of PD in the experimental group was determined again at the end of the study.On the 28-item WHOQOL-BREF scale, the scores of the experimental group were higher than those of the control group on 5 items and the environmental domain at 14 days. There was a significant improvement in the experimental group on 2 items at 28 days and at 90 days after periodontal treatment (both P improvement in the experimental group in total score at 28 and 90 days after periodontal treatment (both P plan for PD care showed some improvement in QoL, including in the environmental domain, and on the total score for OHRQoL. Comprehensive periodontal treatment also alleviated periodontal symptoms.

  7. Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

    Directory of Open Access Journals (Sweden)

    Kazuichi Okazaki

    2012-01-01

    Full Text Available Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team and the other from lymph proliferation (Umehara team supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP, compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.

  8. 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.

  9. The discovery of how gender influences age immunological mechanisms in health and disease, and the identification of ageing gender-specific biomarkers, could lead to specifically tailored treatment and ultimately improve therapeutic success rates

    Directory of Open Access Journals (Sweden)

    Berghella Anna

    2012-11-01

    Full Text Available Abstract The control of human health and diseases in the elderly population is becoming a challenge, since mean age and life expectation are progressively increasing as well as chronic degenerative diseases. These disorders are of complex diagnosis and they are difficult to be treated, but it is hoped that the predictive medicine will lead to more specific and effective treatment by using specific markers to identify persons with high risk of developing disease, before the clinical manifestation. Peripheral blood targets and biomarkers are currently the most practical, non-invasive means of disease diagnosing, predicting prognosis and therapeutic response. Human longevity is directly correlated with the optimal functioning of the immune system. Recent findings indicate that the sexual dimorphism of T helper (Th cytokine pathways and the regulation of Th cell network homeostasis are normally present in the immune response and undergoes to adverse changes with ageing. Furthermore, immune senescence affects both men and women, but it does not affect them equally. Therefore, we hypothesize that the comprehension of the interferences between these gender specific pathways, the ageing immunological mechanism in pathological or healthy state and the current therapies, could lead to specifically tailored treatment and eventually improve the therapeutic success rates. Reaching this aim requires the identification of ageing gender-specific biomarkers that could easily reveal the above mentioned correlations.

  10. Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease.

    Science.gov (United States)

    Lu, Qiyu; Sun, Yi; Duan, Yuyin; Li, Bin; Xia, Jianming; Yu, Songhua; Zhang, Guimin

    2018-03-16

    Valvular heart disease is a leading cause of cardiovascular mortality, especially in China. More than a half of valvular heart diseases are caused by acute rheumatic fever. microRNA is involved in many physiological and pathological processes. However, the miRNA profile of the rheumatic valvular heart disease is unknown. This research is to discuss microRNAs and their target gene pathways involved in rheumatic heart valve disease. Serum miRNA from one healthy individual and four rheumatic heart disease patients were sequenced. Specific differentially expressed miRNAs were quantified by Q-PCR in 40 patients, with 20 low-to-moderate rheumatic mitral valve stenosis patients and 20 severe mitral valve stenosis patients. The target relationship between certain miRNA and predicted target genes were analysis by Luciferase reporter assay. The IL-1β and IL1R1 expression levels were analyzed by immunohistochemistry and western blot in the mitral valve from surgery of mitral valve replacement. The results showed that 13 and 91 miRNAs were commonly upregulated or downregulated in all four patients. Nine miRNAs, 1 upregulated and 8 downregulated, that had a similar fold change in all 4 patients were selected for quantitative PCR verification. The results showed similar results from miRNA sequencing. Within these 9 tested miRNAs, hsa-miR-205-3p and hsa-miR-3909 showed a low degree of dispersion between the members of each group. Hsa miR-205-3p and hsa-miR-3909 were predicted to target the 3'UTR of IL-1β and IL1R1 respectively. This was verified by luciferase reporter assays. Immunohistochemistry and Western blot results showed that the mitral valve from rheumatic valve heart disease showed higher levels of IL- 1β and IL1R1 expression compared with congenital heart valve disease. This suggested a difference between rheumatic heart valve disease and other types of heart valve diseases, with more inflammatory responses in the former. In the present study, by next generation

  11. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

    Directory of Open Access Journals (Sweden)

    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC. Keywords: Metabolomics, Lipid peroxidation, Lipidomics, Myocardial infarction, Isoprostanes, Coronary heart disease (CHD

  12. Comprehensive Study of Honey with Protected Denomination of Origin and Contribution to the Enhancement of Legal Specifications

    Directory of Open Access Journals (Sweden)

    Leticia M. Estevinho

    2012-07-01

    Full Text Available In this study the characterization of a total of 60 honey samples with Protected Denomination of Origin (PDO collected over three harvests (2009–2011, inclusive, from the Northeast of Portugal was carried out based on the presence of pollen, physicochemical and microbiological characteristics. All samples were found to meet the European Legislation, but some didn’t meet the requirements of the PDO specifications. Concerning the floral origin of honey, our results showed the prevalence of rosemary (Lavandula pedunculata pollen. The microbiological quality of all the analyzed samples was satisfactory, since fecal coliforms, sulfite-reducing clostridia and Salmonella were absent, and molds and yeasts were detected in low counts. Significant differences between the results were studied using one-way analysis of variance (ANOVA, followed by Tukey’s HSD test. The samples were submitted to discriminant function analysis, in order to determine which variables differentiate between two or more naturally occurring groups (Forward Stepwise Analysis. The variables selected were in this order: diastase activity, pH, reducing sugars, free acidity and HMF. The pollen spectrum has perfect discriminatory power. This is the first study in which a honey with PDO was tested, in order to assess its compliance with the PDO book of specifications.

  13. 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.

  14. 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.

  15. Comprehensive genetic study of fatty acids helps explain the role of noncoding inflammatory bowel disease associated SNPs and fatty acid metabolism in disease pathogenesis.

    Science.gov (United States)

    Jezernik, Gregor; Potočnik, Uroš

    2018-03-01

    Fatty acids and their derivatives play an important role in inflammation. Diet and genetics influence fatty acid profiles. Abnormalities of fatty acid profiles have been observed in inflammatory bowel diseases (IBD), a group of complex diseases defined by chronic gastrointestinal inflammation. IBD associated fatty acid profile abnormalities were observed independently of nutritional status or disease activity, suggesting a common genetic background. However, no study so far has attempted to look for overlap between IBD loci and fatty acid associated loci or investigate the genetics of fatty acid profiles in IBD. To this end, we conducted a comprehensive genetic study of fatty acid profiles in IBD using iCHIP, a custom microarray platform designed for deep sequencing of immune-mediated disease associated loci. This study identifies 10 loci associated with fatty acid profiles in IBD. The most significant associations were a locus near CBS (p = 7.62 × 10 -8 ) and a locus in LRRK2 (p = 1.4 × 10 -7 ). Of note, this study replicates the FADS gene cluster locus, previously associated with both fatty acid profiles and IBD pathogenesis. Furthermore, we identify 18 carbon chain trans-fatty acids (p = 1.12 × 10 -3 ), total trans-fatty acids (p = 4.49 × 10 -3 ), palmitic acid (p = 5.85 × 10 -3 ) and arachidonic acid (p = 8.58 × 10 -3 ) as significantly associated with IBD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

    Directory of Open Access Journals (Sweden)

    Snigdha Roy

    Full Text Available Fragile X syndrome (FXS is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1 gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP. Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

  17. 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

  18. A comprehensive outlook of Sannipata

    Science.gov (United States)

    Panja, Asit K; Chattopadhyaya, Abichal; Chaudhuri, Supriyo

    2011-01-01

    Nomenclature of the disease on the basis of vitiation of the body humors is stressed in ayurveda. Sannipatika, i.e., ‘conglomeration of vitiated tridosa’ is the final stage of process of manifestation of disease. In this specific state of pathogenesis, the disease becomes more advance and mostly irreversible. A detailed scientific study of Sannipatika-avastha has been documented in classics. Comprehensive analysis of sannipata-state and its ways of presentation is the main theme of the current article. PMID:22408295

  19. 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.

  20. 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.

  1. 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...

  2. 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

  3. 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

  4. Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease.

    Science.gov (United States)

    Chen, Jack J; Swope, David M; Dashtipour, Khashayar

    2007-09-01

    Inhibitors of monoamine oxidase (MAO) with selectivity and specificity for MAO type B (MAO-B) prolong the duration of action of both endogenously and exogenously derived dopamine. Rasagiline [N-propargyl-l(R)-aminoindan] is a second-generation propargylamine pharmacophore that selectively and irreversibly inhibits brain MAO-B and is specifically designed for the treatment of Parkinson's disease (PD). The aim of this study was to review the pharmacology, tolerability, and clinical efficacy of rasagiline in the treatment of PD. MEDLINE (1966-April 2007), the Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970-April 2007) were searched for original research and review articles published in English. The search terms were monoamine oxidase, neuroprotection, Parkinson disease, propargylamine, rasagiline, and selegiline. The reference lists of articles were also consulted, as was information provided by the manufacturer of rasagiline. Data from 63 clinical and laboratory studies were analyzed. Based on the results from those studies, we concluded that rasagiline PO QD, at the therapeutic dosage range of 0.5 to 1 rag/d, is effective and well tolerated and completely, selectively, and specifically inhibited MAO-B. Pharmacologically, rasagiline was found to be Rasagiline was effective both as monotherapy in early PD and as adjunctive treatment in patients with advancing PD and motor fluctuations. As monotherapy, rasagiline provided modest yet clinically meaningful benefit. A randomized, double-blind, placebo-controlled study found that, after 26 weeks of treatment, the adjusted effect size for total Unified Parkinson's Disease Rating Scale score was -4.20 (95% CI, -5.66 to -2.73) for rasagiline 1 mg/d versus placebo (P rasagiline is initiated early (before the need for dopaminergic agents) rather than later. In patients with more advanced disease who received treatment with dopaminergic agents, rasagiline and entacapone were associated

  5. 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.)

  6. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, R.M.; Bhutta, Zulfiqar; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Z.; Coates, M.; Geleijnse, J.M.

    2016-01-01

    Background
    Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249

  7. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, Ryan M.; Bhutta, Zulfiqar A.; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Zian; Coates, Matthew M.; Coggeshall, Megan; Dandona, Lalit; Dicker, Daniel J.; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Foreman, Kyle; Forouzanfar, Mohammad H.; Fraser, Maya S.; Pullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Huynh, Chantal; Johnson, Catherine; Kassebaum, Nicholas J.; Kinfu, Yohannes; Kulikoff, Xie Rachel; Kutz, Michael; Kyu, Hmwe H.; Larson, Heidi J.; Leung, Janni; Liang, Xiaofeng; Lim, Stephen S.; Lind, Margaret; Lozano, Rafael; Marquez, Neal; Mensah, George A.; Mikesell, Joe; Mokdad, Ali H.; Mooney, Meghan D.; Nguyen, Grant; Nsoesie, Elaine; Pigott, David M.; Amare, Azmeraw T.; Hoek, Hans W.; Singh, Abhishek; Tura, Abera Kenay

    2016-01-01

    Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes

  8. 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.

  9. 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.)

  10. 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.)

  11. 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

  12. 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.)

  13. 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

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

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    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.

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

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    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.

  16. 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

  17. 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

  18. 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.

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

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    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.

  20. 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

  1. 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.

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

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    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.

  3. 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.

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

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    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.

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

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    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.

  6. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment.

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    Yasuyuki Nagasawa

    Full Text Available BACKGROUND: Immunoglobulin (IgA nephropathy (IgAN is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse. METHODS AND FINDINGS: We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062. Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012. Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002. Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019. There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046, and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037 by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy. CONCLUSION: This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

  7. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment.

    Science.gov (United States)

    Nagasawa, Yasuyuki; Iio, Kenichiro; Fukuda, Shinji; Date, Yasuhiro; Iwatani, Hirotsugu; Yamamoto, Ryohei; Horii, Arata; Inohara, Hidenori; Imai, Enyu; Nakanishi, Takeshi; Ohno, Hiroshi; Rakugi, Hiromi; Isaka, Yoshitaka

    2014-01-01

    Immunoglobulin (Ig)A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse. We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy. This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

  8. 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.

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

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    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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Comprehensive Assessment of Coronary Artery Disease by Using First-Pass Analysis Dynamic CT Perfusion: Validation in a Swine Model.

    Science.gov (United States)

    Hubbard, Logan; Lipinski, Jerry; Ziemer, Benjamin; Malkasian, Shant; Sadeghi, Bahman; Javan, Hanna; Groves, Elliott M; Dertli, Brian; Molloi, Sabee

    2018-01-01

    Purpose To retrospectively validate a first-pass analysis (FPA) technique that combines computed tomographic (CT) angiography and dynamic CT perfusion measurement into one low-dose examination. Materials and Methods The study was approved by the animal care committee. The FPA technique was retrospectively validated in six swine (mean weight, 37.3 kg ± 7.5 [standard deviation]) between April 2015 and October 2016. Four to five intermediate-severity stenoses were generated in the left anterior descending artery (LAD), and 20 contrast material-enhanced volume scans were acquired per stenosis. All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for FPA perfusion measurement. Perfusion measurements in the LAD, left circumflex artery (LCx), right coronary artery, and all three coronary arteries combined were compared with microsphere perfusion measurements by using regression, root-mean-square error, root-mean-square deviation, Lin concordance correlation, and diagnostic outcomes analysis. The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were also determined. Results FPA and MSM perfusion measurements (P FPA and P MSM ) in all three coronary arteries combined were related to reference standard microsphere perfusion measurements (P MICRO ), as follows: P FPA_COMBINED = 1.02 P MICRO_COMBINED + 0.11 (r = 0.96) and P MSM_COMBINED = 0.28 P MICRO_COMBINED + 0.23 (r = 0.89). The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were 10.8 and 17.8 mGy, respectively. Conclusion The FPA technique was retrospectively validated in a swine model and has the potential to be used for accurate, low-dose vessel-specific morphologic and physiologic assessment of coronary artery disease. © RSNA, 2017.

  18. 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)

  19. 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.

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

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    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.

  1. 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.

  2. 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.

  3. An initial exploration for comprehensive assessment of IgG4-related lung disease: analyses on the cases enrolled from a systematic review.

    Science.gov (United States)

    Wang, An; Fan, Jie; Chen, Xiaofeng; Wang, Shaohua

    2018-03-01

    The existence of two diagnostic systems, the Boston and Japan criteria, for immunoglobulin G4-related disease (IgG4-RD) confuse the medical practice. We aimed to develop a comprehensive assessment based on the weight of each diagnostic item in the existing criteria to improve the diagnostic efficiency of Boston criteria. We assessed the patients enrolled by a systematic review of the literatures using the Boston criteria, Japan criteria and a tentative comprehensive assessment respectively, and evaluated the efficiency of each system and their consistency. Our analysis showed that the distinction in pathological diagnostic items was similar for the Boston criteria (IgG4+/IgG+ ratio, Pcomprehensive assessment (IgG4+/IgG+ ratio and the number of pathological features, Pcomprehensive assessment. The current two diagnostic systems have poor consistency. Comprehensive assessment has good agreement with the Boston criteria, but can identify those cases in Boston Category 3 who could still be diagnosed as IgG4-related lung disease. Considering the weight of diagnostic items, the scoring system is a tentative exploration that should be improved with further experience in diagnosing IgG4-related lung disease.

  4. 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.

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

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    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.

  6. 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

  7. Intermittent Theta-Burst Stimulation of the Right Dorsolateral Prefrontal Cortex to Promote Metaphor Comprehension in Parkinson Disease: A Case Study.

    Science.gov (United States)

    Tremblay, Christina; Monetta, Laura; Langlois, Mélanie; Schneider, Cyril

    2016-01-01

    This single-case research-designed study explored whether intermittent theta-burst stimulation (iTBS) of the right dorsolateral prefrontal cortex (DLPFC) could improve metaphor comprehension in people with Parkinson disease (PD) and language impairments. A right-handed participant with PD diagnosed 9 years ago, receiving long-term treatment with levodopa, and with metaphor comprehension impairment was recruited to undergo 10 sessions of sham stimulation (in 2wk), a washout period (6wk), and then 10 sessions of iTBS (in 2wk). Clinical scores of metaphor comprehension and motor evaluation (Unified Parkinson Disease Rating Scale part III) and transcranial magnetic stimulation to test the excitability of the primary motor cortex (M1) were used at baseline, postsham, post-iTBS, and at 3 follow-ups (8, 14, and 20wk post-iTBS). Metaphor comprehension was improved after iTBS, and the highest scores were obtained 8 weeks later (P=.01). This improvement was correlated with the increase of the right M1 excitability (r=-.86, P=.03) and with the decrease of transcallosal inhibition latency from the left to the right hemisphere (r=-.88, P=.02). Sham yielded no effect (P>.05). Administration of iTBS over the right DLPFC improved metaphor comprehension likely by a long-term influence on brain synaptic plasticity, including improvement of interhemispheric dialogue. More studies are warranted to confirm these findings in larger samples of participants with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. 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.

  10. Comprehensive analysis of area-specific and time-dependent changes in gene expression in the motor cortex of macaque monkeys during recovery from spinal cord injury.

    Science.gov (United States)

    Higo, Noriyuki; Sato, Akira; Yamamoto, Tatsuya; Oishi, Takao; Nishimura, Yukio; Murata, Yumi; Onoe, Hirotaka; Isa, Tadashi; Kojima, Toshio

    2018-05-01

    The present study aimed to assess the molecular bases of cortical compensatory mechanisms following spinal cord injury in primates. To accomplish this, comprehensive changes in gene expression were investigated in the bilateral primary motor cortex (M1), dorsal premotor cortex (PMd), and ventral premotor cortex (PMv) after a unilateral lesion of the lateral corticospinal tract (l-CST). At 2 weeks after the lesion, a large number of genes exhibited altered expression levels in the contralesional M1, which is directly linked to the lesioned l-CST. Gene ontology and network analyses indicated that these changes in gene expression are involved in the atrophy and plasticity changes observed in neurons. Orchestrated gene expression changes were present when behavioral recovery was attained 3 months after the lesion, particularly among the bilateral premotor areas, and a large number of these genes are involved in plasticity. Moreover, several genes abundantly expressed in M1 of intact monkeys were upregulated in both the PMd and PMv after the l-CST lesion. These area-specific and time-dependent changes in gene expression may underlie the molecular mechanisms of functional recovery following a lesion of the l-CST. © 2018 Wiley Periodicals, Inc.

  11. 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.

  12. Methodological approaches to perform a site specific PSA on the effects of comprehensive events; Methodische Ansaetze zur Durchfuehrung einer standortspezifischen PSA zu den Auswirkungen uebergreifender Einwirkungen

    Energy Technology Data Exchange (ETDEWEB)

    Tuerschmann, Michael; Sperbeck, Silvio; Frey, Walter

    2016-12-15

    Main objective of the project 3612R01550 performed on behalf of the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) is the development of an approach for systematic consideration of dependencies in case of internal and external hazards and their combinations in the probabilistic plant model for nuclear power plants. One of the major aspects of a site specific Level 1 PSA carried out for a nuclear power plant outlined in this report is taking comprehensively into account the entire risks resulting from internal and external hazards. In a first step, all the hazards which may occur at the site under investigation have to be identified. This requires a compilation of the potential hazards and their possible combinations: Based on this compilation of generic hazards a site specific list of hazards to be considered in the analysis can be derived based on a screening process taking into account regulatory requirements and insights from site and plant walk-downs. In a second step, the hazards to be considered for the specific site have to be classified with respect to the depth of the probabilistic analyses to be carried out. This classification covers three categories: hazards with a negligible contribution to the overall risk, hazards with such a low risk contribution that a rough quantitative assessment is sufficient, and hazards which need in-depth probabilistic analysis. Based on the available Level 1 PSA model for internal events, a systematic approach for in-depth probabilistic analyses of hazards and their combinations is proposed. In this context, lists of those structures, systems and components, which can be impaired in their required function resulting in a risk increase, are provided. One of these lists contains the equipment, the other one the dependencies to be considered for the corresponding hazard. In addition to the general approach for performing site specific PSA, a procedure for modelling dependencies in

  13. 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

  14. 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

  15. Comprehensive microarray-based analysis for stage-specific larval camouflage pattern-associated genes in the swallowtail butterfly, Papilio xuthus

    Directory of Open Access Journals (Sweden)

    Futahashi Ryo

    2012-05-01

    Full Text Available Abstract Background Body coloration is an ecologically important trait that is often involved in prey-predator interactions through mimicry and crypsis. Although this subject has attracted the interest of biologists and the general public, our scientific knowledge on the subject remains fragmentary. In the caterpillar of the swallowtail butterfly Papilio xuthus, spectacular changes in the color pattern are observed; the insect mimics bird droppings (mimetic pattern as a young larva, and switches to a green camouflage coloration (cryptic pattern in the final instar. Despite the wide variety and significance of larval color patterns, few studies have been conducted at a molecular level compared with the number of studies on adult butterfly wing patterns. Results To obtain a catalog of genes involved in larval mimetic and cryptic pattern formation, we constructed expressed sequence tag (EST libraries of larval epidermis for P. xuthus, and P. polytes that contained 20,736 and 5,376 clones, respectively, representing one of the largest collections available in butterflies. A comparison with silkworm epidermal EST information revealed the high expression of putative blue and yellow pigment-binding proteins in Papilio species. We also designed a microarray from the EST dataset information, analyzed more than five stages each for six markings, and confirmed spatial expression patterns by whole-mount in situ hybridization. Hence, we succeeded in elucidating many novel marking-specific genes for mimetic and cryptic pattern formation, including pigment-binding protein genes, the melanin-associated gene yellow-h3, the ecdysteroid synthesis enzyme gene 3-dehydroecdysone 3b-reductase, and Papilio-specific genes. We also found many cuticular protein genes with marking specificity that may be associated with the unique surface nanostructure of the markings. Furthermore, we identified two transcription factors, spalt and ecdysteroid signal-related E75, as genes

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

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    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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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...

  8. 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.

  9. 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

  10. 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

  11. Towards comprehensive and transparent reporting: context-specific additions to the ICF taxonomy for medical evaluations of work capacity involving claimants with chronic widespread pain and low back pain.

    Science.gov (United States)

    Schwegler, Urban; Anner, Jessica; Glässel, Andrea; Brach, Mirjam; De Boer, Wout; Cieza, Alarcos; Trezzini, Bruno

    2014-08-29

    Medical evaluations of work capacity provide key information for decisions on a claimant's eligibility for disability benefits. In recent years, the evaluations have been increasingly criticized for low transparency and poor standardization. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive spectrum of categories for reporting functioning and its determinants in terms of impairments and contextual factors and could facilitate transparent and standardized documentation of medical evaluations of work capacity. However, the comprehensiveness of the ICF taxonomy in this particular context has not been empirically examined. In this study, we wanted to identify potential context-specific additions to the ICF for its application in medical evaluations of work capacity involving chronic widespread pain (CWP) and low back pain (LBP). A retrospective content analysis of Swiss medical reports was conducted by using the ICF for data coding. Concepts not appropriately classifiable with ICF categories were labeled as specification categories (i.e. context-specific additions) and were assigned to predefined specification areas (i.e. precision, coverage, personal factors, and broad concepts). Relevant specification categories for medical evaluations of work capacity involving CWP and LBP were determined by calculating their relative frequency across reports and setting a relevance threshold. Forty-three specification categories for CWP and fifty-two for LBP reports passed the threshold. In both groups of reports, precision was the most frequent specification area, followed by personal factors. The ICF taxonomy represents a universally applicable standard for reporting health and functioning information. However, when applying the ICF for comprehensive and transparent reporting in medical evaluations of work capacity involving CWP and LBP context-specific additions are needed. This is particularly true for the documentation of

  12. 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

  13. 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....

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. 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

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

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    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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Circulating biomarkers for predicting cardiovascular disease risk : a systematic review and comprehensive overview of meta-analyses

    NARCIS (Netherlands)

    Holten, van T.C.; Waanders, L.F.; Groot, de P.G.; Vissers, J.; Hoefer, I.E.; Pasterkamp, G.; Prins, M.W.J.; Roest, M.

    2013-01-01

    Background : Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming

  9. [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.

  10. 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

  11. Implementation of Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Health Authority by the Agency for Toxic Substances and Disease Registry

    International Nuclear Information System (INIS)

    Siegel, M.R.

    1990-01-01

    The Superfund Amendments and Reauthorization Act (SARA) of 1986 greatly expanded the health authority of the Comprehensive Environmental Response, Compensation, and Liability Act. One of the federal agencies most affected by SARA is the Agency for Toxic Substances and Disease Registry (ATSDR) of the U.S. Public Health Service. Among other responsibilities, ATSDR was mandated to conduct health assessments within strict time frames for each site on or proposed for the U.S. Environmental Protection Agency's National Priorities List. The author will review ATSDR's efforts to address this new statutory mandate, especially for federal facilities, and will focus on different conceptual frameworks for implementing the health assessment program

  12. 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.

  13. 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.

  14. 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.

  15. 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.)

  16. 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.)

  17. 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

  18. 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.

  19. An essay on Wilhelm von Humboldt and the shaking palsy: first comprehensive description of Parkinson's disease by a patient.

    Science.gov (United States)

    Horowski, R; Horowski, L; Vogel, S; Poewe, W; Kielhorn, F W

    1995-03-01

    James Parkinson first described what is now known as Parkinson's disease in his essay in 1817 on the shaking palsy, but the disease became well-known to neurologists only in the second half of the 19th century. In his letters from 1828 until his death in 1835, Wilhelm von Humboldt, a well-known German academic reformer, humanist scholar, and statesman, precisely described the manifestations of this disease. These included resting tremor and especially problems in writing, called by him "a special clumsiness" that he attributed to a disturbance in executing rapid complex movements. In addition to lucidly describing akinesia, he was also the first to describe micrographia. He furthermore noticed his typical parkinsonian posture and, in all probability, his rigidity as "internal tremor not visible by others which causes a distortion of the continuity of my movements." He insisted, however, that he was suffering not from a disease but just from accelerated aging related to the death of his wife. His description of the disease is more complete than the observations and definition by James Parkinson; his attitude toward his disease illustrates why it was not readily accepted as a disease in itself but might have been considered an extreme variant of aging instead.

  20. Development of comprehensive image processing technique for differential diagnosis of liver disease by using multi-modality images. Pixel-based cross-correlation method using a profile

    International Nuclear Information System (INIS)

    Inoue, Akira; Okura, Yasuhiko; Akiyama, Mitoshi; Ishida, Takayuki; Kawashita, Ikuo; Ito, Katsuyoshi; Matsunaga, Naofumi; Sanada, Taizo

    2009-01-01

    Imaging techniques such as high magnetic field imaging and multidetector-row CT have been markedly improved recently. The final image-reading systems easily produce more than a thousand diagnostic images per patient. Therefore, we developed a comprehensive cross-correlation processing technique using multi-modality images, in order to decrease the considerable time and effort involved in the interpretation of a radiogram (multi-formatted display and/or stack display method, etc). In this scheme, the criteria of an attending radiologist for the differential diagnosis of liver cyst, hemangioma of liver, hepatocellular carcinoma, and metastatic liver cancer on magnetic resonance images with various sequences and CT images with and without contrast enhancement employ a cross-correlation coefficient. Using a one-dimensional cross-correlation method, comprehensive image processing could be also adapted for various artifacts (some depending on modality imaging, and some on patients), which may be encountered at the clinical scene. This comprehensive image-processing technique could assist radiologists in the differential diagnosis of liver diseases. (author)

  1. 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

  2. Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: A comprehensive review of the literature

    NARCIS (Netherlands)

    B. Schoser; Fong, E. (Edward); Geberhiwot, T. (Tarekegn); Hughes, D. (Derralynn); Kissel, J.T. (John T.); Madathil, S.C. (Shyam C.); Orlikowski, D. (David); Polkey, M.I. (Michael I.); M. Roberts (Mark); H.A.W.M. Tiddens (Harm); Young, P. (Peter)

    2017-01-01

    textabstractRespiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle

  3. [Management programs on diabetes among Chinese adults in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

    Science.gov (United States)

    Jin, R R; Li, J J; Zhang, J; Li, J L; Bian, F; Deng, G J; Ma, S; Su, X W; Zhao, J; Jiang, Y

    2018-04-10

    Objective: To understand the current situation on management of diabetes mellitus patients aged 35 and above in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases, in China. Methods: Local residents, aged 18 years and above were randomly selected by a complex, multistage, probability sampling method. Face-to-face questionnaire survey was carried out between November and December 2016. Rates regarding prevalence, treatment and management of diabetes were calculated, and influencing factors of diabetes were analyzed by using the non-conditional logistic regression model. Results: A total of 3 213 residents aged ≥35 years were included in this study, of which 11.48% (369/3 213) reported that they had ever been informed by a doctor or other health worker that their blood sugar level was high or being diabetic. The rate of self-reported treatment among the diabetic patients was 83.20% (307/369). Rates on overall management and standardized management were 69.92% (258/369) and 53.66% (198/369), respectively. Higher rates were seen in residents aged 55 to 64 years, 76.32% for overall management and 59.65% for standardized management. Through multiple logistic regression analysis, we found that standardized management for diabetes was much higher in the Demonstration Areas located in the eastern areas ( OR =2.942, 95% CI : 1.547-5.594), or patients with characteristics including high implementation score ( OR =3.499, 95% CI : 1.865-6.563), already signed family doctors ( OR =5.661, 95% CI : 3.237-9.899), or without hypertension ( OR =1.717, 95% CI : 1.010- 2.920). Residents who were living in the first and second batch areas of implementation or responding to the NCDs with positive attitude were more likely to accept standardized management. Conclusion: Prevention and management programs on diabetes had met the requirements set for the Demonstration Areas which had promoted the specific implementation and further

  4. 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....

  5. 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

  6. 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.

  7. Radiotherapy options for localized prostate cancer based upon pretreatment serum prostate-specific antigen levels and biochemical control: A comprehensive review of the literature

    International Nuclear Information System (INIS)

    Vicini, Frank A.; Horwitz, Eric M.; Kini, Vijay R.; Stromberg, Jannifer S.; Martinez, Alvaro A.

    1998-01-01

    Purpose: To review all the available radiotherapy (RT) literature on localized prostate cancer treatment where serum prostate-specific antigen (PSA) levels were used to both stratify patients and evaluate outcome and determine if any conclusions can be reached regarding an optimal radiotherapeutic management for this disease. Methods and Materials: A MEDLINE search was conducted to obtain all articles in English on prostate cancer treatment employing RT from 1986-1997. Studies were considered eligible for review only if they met all the following criteria: 1) pretreatment PSA values were recorded and grouped for subsequent evaluation, 2) posttreatment PSA values were continuously monitored, 3) definitions of biochemical control were stated, and 4) the median follow-up was given. Results: Of the 246 articles identified, only 20 met the inclusion criteria; 4 using conformal external beam RT, 8 using conventional external beam RT, and 8 using interstitial brachytherapy (4 using a permanent implant alone, 3 combining external beam RT with a permanent implant, and 1 combining a conformal temporary interstitial implant boost with external beam RT). No studies using neutrons (with or without external beam RT) or androgen deprivation (combined with external beam RT) were identified where patients were stratified by pretreatment PSA levels. Results for all therapies were extremely variable with the 3-5-year rates of biochemical control for patients with pretreatment PSA levels ≤4 ng/ml ranging from 48 to 100%, for PSA levels >4 and ≤10 ng/ml ranging from 44 to 90%, for PSA levels >10 and ≤20 ng/ml ranging from 27 to 89%, and for PSA levels >20 ranging from 14 to 89%. The median Gleason score, T-stage, definition of biochemical control, and follow-up were substantially different from series to series. No RT option consistently produced superior results. Conclusions: When data are reviewed from studies using serum PSA levels to stratify patients and to evaluate

  8. 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...

  9. 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

  10. 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

  11. 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...

  12. Clinical performance improvement series. Classic CQI integrated with comprehensive disease management as a model for performance improvement.

    Science.gov (United States)

    Joshi, M S; Bernard, D B

    1999-08-01

    In recent years, health and disease management has emerged as an effective means of delivering, integrating, and improving care through a population-based approach. Since 1997 the University of Pennsylvania Health System (UPHS) has utilized the key principles and components of continuous quality improvement (CQI) and disease management to form a model for health care improvement that focuses on designing best practices, using best practices to influence clinical decision making, changing processes and systems to deploy and deliver best practices, and measuring outcomes to improve the process. Experience with 28 programs and more than 14,000 patients indicates significant improvement in outcomes, including high physician satisfaction, increased patient satisfaction, reduced costs, and improved clinical process and outcome measures across multiple diseases. DIABETES DISEASE MANAGEMENT: In three months a UPHS multidisciplinary diabetes disease management team developed a best practice approach for the treatment of all patients with diabetes in the UPHS. After the program was pilot tested in three primary care physician sites, it was then introduced progressively to additional practice sites throughout the health system. The establishment of the role of the diabetes nurse care managers (certified diabetes educators) was central to successful program deployment. Office-based coordinators ensure incorporation of the best practice protocols into routine flow processes. A disease management intranet disseminates programs electronically. Outcomes of the UPHS health and disease management programs so far demonstrate success across multiple dimensions of performance-service, clinical quality, access, and value. The task of health care leadership today is to remove barriers and enable effective implementation of key strategies, such as health and disease management. Substantial effort and resources must be dedicated to gain physician buy-in and achieve compliance. The

  13. 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

  14. 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

  15. A rehabilitation model as key to comprehensive care in the era of HIV as a chronic disease in South Africa.

    Science.gov (United States)

    Chetty, Verusia; Hanass-Hancock, Jill

    2016-01-01

    In the era of widespread access to antiretroviral therapy, people living with HIV survive; however, this comes with new experiences of comorbidities and HIV-related disability posing new challenges to rehabilitation professionals and an already fragile health system in Southern Africa. Public health approaches to HIV need to include not only prevention, treatment and support but also rehabilitation. While some well-resourced countries have developed rehabilitation approaches for HIV, resource-poor settings of Southern Africa lack a model of care that includes rehabilitation approaches providing accessible and comprehensive care for people living with HIV. In this study, a learning in action approach was used to conceptualize a comprehensive model of care that addresses HIV-related disability and a feasible rehabilitation framework for resource-poor settings. The study used qualitative methods in the form of a focus group discussion with thirty participants including people living with HIV, the multidisciplinary healthcare team and community outreach partners at a semi-rural health facility in South Africa. The discussion focused on barriers and enablers of access to rehabilitation. Participants identified barriers at various levels, including transport, physical access, financial constraints and poor multi-stakeholder team interaction. The results of the group discussions informed the design of an inclusive model of HIV care. This model was further informed by established integrated rehabilitation models. Participants emphasized that objectives need to respond to policy, improve access to patient-centered care and maintain a multidisciplinary team approach. They proposed that guiding principles should include efficient communication, collaboration of all stakeholders and leadership in teams to enable staff to implement the model. Training of professional staff and lay personnel within task-shifting approaches was seen as an essential enabler to implementation. The

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Metacognitive and language-specific knowledge in native and foreign language reading comprehension: an emprical study among Dutch students in grades 6, 8 and 10

    NARCIS (Netherlands)

    Schoonen, R.; Hulstijn, J.; Bossers, B.

    1998-01-01

    This article gives the results of a study among 685 students in grades 6, 8 and 10 in the Netherlands to whom we administered grade-appropriate measures of reading comprehension and vocabulary knowledge in their native language (NL), Dutch, as well as, in grades 8 and 10, in English as a foreign

  1. 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.

  2. 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

  3. 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.

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

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    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.

  5. Comprehensive analysis of three TYK2 gene variants in the susceptibility to Chagas disease infection and cardiomyopathy

    Science.gov (United States)

    Carmona, F. David; Dolade, Nuria; Vargas, Sofia; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2018-01-01

    Tyrosine kinase 2 (TYK2) is a member of the Janus kinases family implicated in the signal transduction of type I interferons and several interleukins. It has been described that genetic mutations within TYK2 lead to multiple deleterious effects in the immune response. In this work, we have analyzed three functional independent variants from the frequency spectrum on the TYK2 gene (common and low-frequency variants) suggested to reduce the function of the gene in mediating cytokine signaling and the susceptibility to infections by Trypanosoma cruzi and/or the development of Chagas cardiomyopathy in the Colombian population. A total of 1,323 individuals from a Colombian endemic region for Chagas disease were enrolled in the study. They were classified as seronegative (n = 445), seropositive asymptomatic (n = 336), and chronic Chagas Cardiomyopathy subjects (n = 542). DNA samples were genotyped using TaqMan probes. Our results showed no statistically significant differences between the allelic frequencies of the three analyzed variants when seropositive and seronegative individuals were compared, therefore these variants were not associated with susceptibility to Chagas disease. Moreover, when Chagas cardiomyopathy patients were compared to asymptomatic patients, no significant associations were found. Previous reports highlighted the association of this gene in immune-related disorders under an autoimmunity context, but not predisposing patients to infectious diseases, which is consistent with our findings. Therefore, according to our results, TYK2 gene variants do not seem to play an important role in Chagas disease susceptibility and/or chronic Chagas cardiomyopathy. PMID:29304122

  6. Glia Open Access Database (GOAD) : A comprehensive gene expression encyclopedia of glia cells in health and disease

    NARCIS (Netherlands)

    Holtman, Inge R.; Noback, Michiel; Bijlsma, Marieke; Duong, Kim N.; van der Geest, Marije A.; Ketelaars, Peer T.; Brouwer, Nieske; Vainchtein, Ilia D.; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.

    Recently, the number of genome-wide transcriptome profiles of pure populations of glia cells has drastically increased, resulting in an unprecedented amount of data that offer opportunities to study glia phenotypes and functions in health and disease. To make genome-wide transcriptome data easily

  7. 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.

  8. Who will deliver comprehensive healthy lifestyle interventions to combat non-communicable disease? Introducing the healthy lifestyle practitioner discipline.

    Science.gov (United States)

    Arena, Ross; Lavie, Carl J; Hivert, Marie-France; Williams, Mark A; Briggs, Paige D; Guazzi, Marco

    2016-01-01

    Unhealthy lifestyle characteristics (i.e., physical inactivity, excess body mass, poor diet, and smoking) as well as associated poor health metrics (i.e., dyslipidemia, hyperglycemia, and hypertension) are the primary reasons for the current non-communicable disease crisis. Compared to those with the poorest of lifestyles and associated health metrics, any movement toward improving lifestyle and associated health metrics improves health outcomes. To address the non-communicable disease crisis we must: 1) acknowledge that healthy lifestyle (HL) interventions are a potent medicine; and 2) move toward a healthcare system that embraces primordial as much as, if not more than, secondary prevention with a heavy focus on HL medicine. This article introduces the Healthy Lifestyle Practitioner, focused on training health professionals to deliver HL medicine.

  9. 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.

  10. Asthma and other allergic diseases among Saudi schoolchildren in Najran: the need for a comprehensive intervention program.

    Science.gov (United States)

    Alqahtani, Jobran M

    2016-01-01

    In the last three decades, an increasing incidence of allergic diseases has been associated with increasing morbidity and mortality in children and young adults. The study aimed to investigate the prevalence and risk factors associated with allergic diseases among Saudi schoolchildren in the southwestern Saudi region of Najran, and to determine the sensitization of patients to a set of allergens. Cross-sectional observational study. Primary, intermediate and secondary schools, Najran, Saudi Arabia. All participants completed the Arabic version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Skin prick tests (SPT) were performed, using a panel of standardized allergenic extracts. Prevalence and risk factors associated with pediatric allergic diseases. The study included 1700 Saudi schoolchildren. The overall prevalence of physician-diagnosed asthma, allergic rhinitis and atopic dermatitis was 27.5%, 6.3% and 12.5%, respectively. Multivariate analysis showed that male gender (adjusted odds ratio [aOR], 1.27), fast food consumption (aOR, 1.53), trucks passing near houses (aOR, 1.86), and having a dog or cat at home (aOR, 1.85) were significant risk factors. A total of 722 (42.5%) children had a positive SPT result to at least one allergen. The most prevalent allergens were grass pollens (60%), cat fur (41.6%), and house dust mites (25%). The findings of this study highlight the urgent need for developing an effective interven- tion program including several components working in harmony to control and reduce the burden of allergic diseases. These results may not be generalizable to the rest of Saudi Arabia.

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

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    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

  12. A comprehensive questionnaire for the assessment of health-related quality of life in coeliac disease (CDQL)

    DEFF Research Database (Denmark)

    Skjerning, Halfdan; Hourihane, Jonathan O'b; Husby, Steffen

    2017-01-01

    and qualitative analysis of verbatim transcripts generated CD-specific items for a prototype instrument to sensitively captured patient concerns. In phase 2, CD patients completed the prototype CDQL. The questionnaire was refined through analysis of data and cognitive interviewing. In phase 3, the final version...

  13. 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.

  14. 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.

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

    Science.gov (United States)

    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.

  16. Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

    Science.gov (United States)

    San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

    2014-06-06

    Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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

  19. 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.

  20. Novel MLPA procedure using self-designed probes allows comprehensive analysis for CNVs of the genes involved in Hirschsprung disease

    Directory of Open Access Journals (Sweden)

    Antiñolo Guillermo

    2010-05-01

    Full Text Available Abstract Background Hirschsprung disease is characterized by the absence of intramural ganglion cells in the enteric plexuses, due to a fail during enteric nervous system formation. Hirschsprung has a complex genetic aetiology and mutations in several genes have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis. In this study, we have looked for CNVs in some of the genes related to Hirschsprung (EDNRB, GFRA1, NRTN and PHOX2B using the Multiple Ligation-dependent Probe Amplification (MLPA approach. Methods CNVs screening was performed in 208 HSCR patients using a self-designed set of MLPA probes, covering the coding region of those genes. Results A deletion comprising the first 4 exons in GFRA1 gene was detected in 2 sporadic HSCR patients and in silico approaches have shown that the critical translation initiation signal in the mutant gene was abolished. In this study, we have been able to validate the reliability of this technique for CNVs screening in HSCR. Conclusions The implemented MLPA based technique presented here allows CNV analysis of genes involved in HSCR that have not been not previously evaluated. Our results indicate that CNVs could be implicated in the pathogenesis of HSCR, although they seem to be an uncommon molecular cause of HSCR.

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

    Science.gov (United States)

    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.

  2. 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

  3. 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.

  4. Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases.

    Science.gov (United States)

    Liu, Peng; Wang, Boshi; Yan, Xia; Cai, Jingjing; Wang, Yu

    2016-12-01

    To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases. This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms. After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with 100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk, compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT, compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT. Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment

  5. 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...

  6. 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

  7. A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial) - design, intervention, and population

    DEFF Research Database (Denmark)

    Zwisler, A.D.O.; Schou, O.; Soja, A.M.B.

    2005-01-01

    , or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor...... that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high...

  8. A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial)--design, intervention, and population

    DEFF Research Database (Denmark)

    Zwisler, Ann-Dorthe Olsen; Soja, Anne Merete Boas; Brønnum-Hansen, Henrik

    2005-01-01

    , or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor...... that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer's disease: ADAS-cog subscale results from the Alphase Study.

    Science.gov (United States)

    Saumier, D; Duong, A; Haine, D; Garceau, D; Sampalis, J

    2009-11-01

    Tramiprosate (homotaurine, ALZHEMEDTM) was recently investigated for its efficacy, safety and disease-modification effects in a Phase III clinical study in mild to moderate Alzheimer's disease (AD) patients (the Alphase study). The primary cognitive endpoint measure of that study was the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). To characterize potential cognitive benefits of tramiprosate, the present study describes exploratory analyses performed on scores obtained from the specific ADAS-cog subscales in order to determine whether specific domains of cognition may be differentially affected by tramiprosate, which would not have been evident from the measure's total score. Multi-center, double-blind, randomized, placebo-controlled study. 67 investigative sites in the United States and Canada. A total of 1,052 patients were randomized. Patients were randomized to receive twice a day Placebo (n=353), tramiprosate 100 mg (n=352) and tramiprosate 150 mg (n=347). ADAS-cog assessments were conducted every three months over the 78-week study period. Exploratory analyses were performed by comparing ADAS-cog subscale scores between Placebo and each active treatment arm at each visit. The findings of this analysis revealed statistically significant differences or statistical trends in favour of tramiprosate on six ADAS-cog subscales, namely Following Commands, Language Comprehension, Ideational Praxis, Object Naming, Remembering Test Instructions, and Spoken Language Ability. Differences in favor of Placebo were only observed on the Constructional Praxis subscale. This exploratory analysis suggests that tramiprosate may have some benefit on memory, language and praxis skills in mild to moderate AD individuals. Future clinical studies of tramiprosate should include specialized neuropsychological tests to validate its effects within these cognitive domains.

  17. 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.

  18. 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

  19. 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

  20. 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...

  1. 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…

  2. 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

  3. 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

  4. Validation of an Accelerometer to Quantify a Comprehensive Battery of Gait Characteristics in Healthy Older Adults and Parkinson's Disease: Toward Clinical and at Home Use.

    Science.gov (United States)

    Del Din, Silvia; Godfrey, Alan; Rochester, Lynn

    2016-05-01

    Measurement of gait is becoming important as a tool to identify disease and disease progression, yet to date its application is limited largely to specialist centers. Wearable devices enables gait to be measured in naturalistic environments, however questions remain regarding validity. Previous research suggests that when compared with a laboratory reference, measurement accuracy is acceptable for mean but not variability or asymmetry gait characteristics. Some fundamental reasons for this have been presented, (e.g., synchronization, different sampling frequencies) but to date this has not been systematically examined. The aims of this study were to: 1) quantify a comprehensive range of gait characteristics measured using a single triaxial accelerometer-based monitor; 2) examine outcomes and monitor performance in measuring gait in older adults and those with Parkinson's disease (PD); and 3) carry out a detailed comparison with those derived from an instrumented walkway to account for any discrepancies. Fourteen gait characteristics were quantified in 30 people with incident PD and 30 healthy age-matched controls. Of the 14 gait characteristics compared, agreement between instruments was excellent for four (ICCs 0.913-0.983); moderate for four (ICCs 0.508-0.766); and poor for six characteristics (ICCs 0.637-0.370). Further analysis revealed that differences reflect an increased sensitivity of accelerometry to detect motion, rather than measurement error. This is most likely because accelerometry measures gait as a continuous activity rather than discrete footfall events, per instrumented tools. The increased sensitivity shown for these characteristics will be of particular interest to researchers keen to interpret "real-world" gait data. In conclusion, use of a body-worn monitor is recommended for the measurement of gait but is likely to yield more sensitive data for asymmetry and variability features.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Memory and Comprehension for Health Information among Older Adults: Distinguishing the Effects of Domain-General and Domain-Specific Knowledge

    Science.gov (United States)

    Chin, Jessie; Payne, Brennan; Gao, Xuefei; Conner-Garcia, Thembi; Graumlich, James F.; Murray, Michael D.; Morrow, Daniel G.; Stine-Morrow, Elizabeth A.L.

    2014-01-01

    While there is evidence that knowledge influences understanding of health information, less is known about the processing mechanisms underlying this effect and its impact on memory. We used the moving window paradigm to examine how older adults varying in domain-general crystallized ability (verbal ability) and health knowledge allocate attention to understand health and domain-general texts. Participants (n=107, aged 60 to 88 yrs) read and recalled single sentences about hypertension and about non-health topics. Mixed-effects modeling of word-by-word reading times suggested that domain-general crystallized ability increased conceptual integration regardless of text domain, while health knowledge selectively increased resource allocation to conceptual integration at clause boundaries in health texts. These patterns of attentional allocation were related to subsequent recall performance. Although older adults with lower levels of crystallized ability were less likely to engage in integrative processing, when they did, this strategy had a compensatory effect in improving recall. These findings suggest that semantic integration during reading is an important comprehension process that supports the construction of the memory representation and is engendered by knowledge. Implications of the findings for theories of text processing and memory as well as for designing patient education materials are discussed. PMID:24787361

  12. Memory and comprehension for health information among older adults: distinguishing the effects of domain-general and domain-specific knowledge.

    Science.gov (United States)

    Chin, Jessie; Payne, Brennan; Gao, Xuefei; Conner-Garcia, Thembi; Graumlich, James F; Murray, Michael D; Morrow, Daniel G; Stine-Morrow, Elizabeth A L

    2015-01-01

    While there is evidence that knowledge influences understanding of health information, less is known about the processing mechanisms underlying this effect and its impact on memory. We used the moving window paradigm to examine how older adults varying in domain-general crystallised ability (verbal ability) and health knowledge allocate attention to understand health and domain-general texts. Participants (n = 107, age: 60-88 years) read and recalled single sentences about hypertension and about non-health topics. Mixed-effects modelling of word-by-word reading times suggested that domain-general crystallised ability increased conceptual integration regardless of text domain, while health knowledge selectively increased resource allocation to conceptual integration at clause boundaries in health texts. These patterns of attentional allocation were related to subsequent recall performance. Although older adults with lower levels of crystallised ability were less likely to engage in integrative processing, when they did, this strategy had a compensatory effect in improving recall. These findings suggest that semantic integration during reading is an important comprehension process that supports the construction of the memory representation and is engendered by knowledge. Implications of the findings for theories of text processing and memory as well as for designing patient education materials are discussed.

  13. 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...

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT genomic binding patterns discerns cell-specific cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Kang Keunsoo

    2013-01-01

    Full Text Available Abstract Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM, which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors.

  19. [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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  5. 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...

  6. 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.

  7. 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.

  8. 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.

  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. 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.

  11. Calcium Hypothesis of Alzheimer's disease and brain aging: A framework for integrating new evidence into a comprehensive theory of pathogenesis.

    Science.gov (United States)

    2017-02-01

    This article updates the Calcium Hypothesis of Alzheimer's disease and brain aging on the basis of emerging evidence since 1994 (The present article, with the subtitle "New evidence for a central role of Ca 2+ in neurodegeneration," includes three appendices that provide context and further explanations for the rationale for the revisions in the updated hypothesis-the three appendices are as follows: Appendix I "Emerging concepts on potential pathogenic roles of [Ca 2+ ]," Appendix II "Future studies to validate the central role of dysregulated [Ca 2+ ] in neurodegeneration," and Appendix III "Epilogue: towards a comprehensive hypothesis.") (Marx J. Fresh evidence points to an old suspect: calcium. Science 2007; 318:384-385). The aim is not only to re-evaluate the original key claims of the hypothesis with a critical eye but also to identify gaps in knowledge required to validate relevant claims and delineate additional studies and/or data that are needed. Some of the key challenges for this effort included examination of questions regarding (1) the temporal and spatial relationships of molecular mechanisms that regulate neuronal calcium ion (Ca 2+ ), (2) the role of changes in concentration of calcium ion [Ca 2+ ] in various subcellular compartments of neurons, (3) how alterations in Ca 2+ signaling affect the performance of neurons under various conditions, ranging from optimal functioning in a healthy state to conditions of decline and deterioration in performance during aging and in disease, and (4) new ideas about the contributions of aging, genetic, and environmental factors to the causal relationships between dysregulation of [Ca 2+ ] and the functioning of neurons (see Appendices I and II). The updated Calcium Hypothesis also includes revised postulates that are intended to promote further crucial experiments to confirm or reject the various predictions of the hypothesis (see Appendix III). Copyright © 2016 the Alzheimer's Association. All rights reserved.

  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. Genetics in primary health care and the National Policy on Comprehensive Care for People with Rare Diseases in Brazil: opportunities and challenges for professional education.

    Science.gov (United States)

    Melo, Débora Gusmão; de Paula, Pamela Karen; de Araujo Rodrigues, Stephania; da Silva de Avó, Lucimar Retto; Germano, Carla Maria Ramos; Demarzo, Marcelo Marcos Piva

    2015-07-01

    As discoveries regarding the genetic contribution to disease have grown rapidly, health care professionals are expected to incorporate genetic and genomic perspectives into health education and practice. Genetic competencies common to all health professionals have been identified by the US National Coalition for Health Professional Education in Genetics (NCHPEG), which defined the knowledge, skills, and attitudes required to achieve these competencies. The aim of this study is to analyze genetic competencies of primary health care professionals in Brazil. It is a descriptive survey study, whereby doctors, nurses, and dentists were invited to participate by answering a questionnaire including 11 issues based on competencies established by the NCHPEG. Data were presented as percentages. Differences between groups of participants were assessed by the Fisher exact test, with the level of significance set at p < 0.05. Results showed that concerning knowledge, about 80 % of the participants recognized basic genetics terminology, but practitioners had difficulty in identifying patterns of inheritance. Regarding clinical skills, practitioners were able to recognize facial dysmorphias and identify situations where referral of patients to specialists was necessary. Nevertheless, there were challenges in the process of valuing and gathering information about family history. Regarding attitudes, 68.9 % of the participants thought about the comprehensiveness of care but faced challenges in counselling parents. The results of this study may contribute to developing an ongoing education program for primary health care professionals, leading to a strategy to overcome the challenges of including genetics in the Brazilian Unified Health System.

  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. 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.)

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  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. 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.

  3. Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

    Directory of Open Access Journals (Sweden)

    Seung-Joo Hyun

    2017-11-01

    Full Text Available To define whether individual human leukocyte antigen (HLA class I allotypes are used preferentially in human cytomegalovirus (CMV-specific cytotoxic T lymphocyte responses, CD8+ T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C present in 50 healthy Korean donors. The CD8+ T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8+ T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.

  4. Children with Specific Language Impairment and Their Families: A Future View of Nature Plus Nurture and New Technologies for Comprehensive Language Intervention Strategies.

    Science.gov (United States)

    Rice, Mabel L

    2016-11-01

    Future perspectives on children with language impairments are framed from what is known about children with specific language impairment (SLI). A summary of the current state of services is followed by discussion of how these children can be overlooked and misunderstood and consideration of why it is so hard for some children to acquire language when it is effortless for most children. Genetic influences are highlighted, with the suggestion that nature plus nurture should be considered in present as well as future intervention approaches. A nurture perspective highlights the family context of the likelihood of SLI for some of the children. Future models of the causal pathways may provide more specific information to guide gene-treatment decisions, in ways parallel to current personalized medicine approaches. Future treatment options can build on the potential of electronic technologies and social media to provide personalized treatment methods available at a time and place convenient for the person to use as often as desired. The speech-language pathologist could oversee a wide range of treatment options and monitor evidence provided electronically to evaluate progress and plan future treatment steps. Most importantly, future methods can provide lifelong language acquisition activities that maintain the privacy and dignity of persons with language impairment, and in so doing will in turn enhance the effectiveness of speech-language pathologists. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. 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

  6. 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).

  7. 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.

  8. 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...

  9. 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...

  10. 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

  11. 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...

  12. 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

  13. 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.

  14. 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 ...

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. Facilitating nurses’ knowledge of the utilisation of reflexology in adults with chronic diseases to enable informed health education during comprehensive nursing care

    Directory of Open Access Journals (Sweden)

    Elna Steenkamp

    2012-05-01

    Full Text Available An integrative literature review of identified scientific evidence, published from January 2000 to December 2008, of the utilisation of reflexology as complementary and alternative medicine (CAM modalities to promote well-being and quality of life in adults with chronic diseases was done to facilitate nurses to give informed health education during comprehensive nursing care to patients with chronic diseases. Selected accessible databases were searched purposefully for research articles (N = 1171. Pre-set inclusion criteria were applied during the study selection process. The methodological study quality was reviewed and appraised with appropriate tools from the Critical Appraisal Skills Programme (CASP and the American Dietetic Association’s (ADA Evidence analysis manual (n = 21. Evidence extraction, analysis and synthesis of studies (n = 18 were done through the evidence class rating and level of strength as prescribed in the manuals of ADA and CASP. Findings indicate statistically significant reduction in the frequency of seizures in patients with intractable epilepsy, an improvement of sensory and urinary symptoms associated with multiple sclerosis and clinically significant reduction of anxiety and pain in patients with cancer and fibromyalgia syndrome. These findings can be utilised by nurses to inform patients with these chronic diseases about alternative ways of treatment. Opsomming ‘n Geïntegreerde literatuur oorsig van ge-identifiseerde wetenskaplike bewyse, gepubliseer vanaf Januarie 2000 tot Desember 2008, was gedoen oor die gebruik van refleksologie as aanvullende en alternatiewe behandelingsmodalitieit om welsyn en lewenskwaliteit te bevorder by volwassenes met kroniese siekte om verpleegkundiges te fasiliteer om ingeligte gesondheidsvoorligting te gee gedurende omvattende verpleegsorg aan pasiente met kroniese siektes. Geselekteerde toeganklike databasisse was doelbewustelik deursoek vir navorsingsartikels (N = 1171. Vooraf

  20. miRTrail - a comprehensive webserver for analyzing gene and miRNA patterns to enhance the understanding of regulatory mechanisms in diseases

    Directory of Open Access Journals (Sweden)

    Laczny Cedric

    2012-02-01

    Full Text Available Abstract Background Expression profiling provides new insights into regulatory and metabolic processes and in particular into pathogenic mechanisms associated with diseases. Besides genes, non-coding transcripts as microRNAs (miRNAs gained increasing relevance in the last decade. To understand the regulatory processes of miRNAs on genes, integrative computer-aided approaches are essential, especially in the light of complex human diseases as cancer. Results Here, we present miRTrail, an integrative tool that allows for performing comprehensive analyses of interactions of genes and miRNAs based on expression profiles. The integrated analysis of mRNA and miRNA data should generate more robust and reliable results on deregulated pathogenic processes and may also offer novel insights into the regulatory interactions between miRNAs and genes. Our web-server excels in carrying out gene sets analysis, analysis of miRNA sets as well as the combination of both in a systems biology approach. To this end, miRTrail integrates information on 20.000 genes, almost 1.000 miRNAs, and roughly 280.000 putative interactions, for Homo sapiens and accordingly for Mus musculus and Danio rerio. The well-established, classical Chi-squared test is one of the central techniques of our tool for the joint consideration of miRNAs and their targets. For interactively visualizing obtained results, it relies on the network analyzers and viewers BiNA or Cytoscape-web, also enabling direct access to relevant literature. We demonstrated the potential of miRTrail by applying our tool to mRNA and miRNA data of malignant melanoma. MiRTrail identified several deregulated miRNAs that target deregulated mRNAs including miRNAs hsa-miR-23b and hsa-miR-223, which target the highest numbers of deregulated mRNAs and regulate the pathway "basal cell carcinoma". In addition, both miRNAs target genes like PTCH1 and RASA1 that are involved in many oncogenic processes. Conclusions The application

  1. [Current status on prevalence, treatment and management of hypertension among Chinese adults in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

    Science.gov (United States)

    Jin, R R; Zhang, J; Li, J L; Li, J J; Ma, S; Bian, F; Deng, G J; Su, X W; Shen, Z Z; Wang, Y P; Jiang, Y

    2018-04-10

    Objective: To investigate the current status of prevalence, treatment, and management on hypertension among Chinese adults from the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: We selected a total of 4 000 residents aged ≥18 years for this questionnaire-based survey by multi-stage clustering sampling in 10 National Demonstration Areas between November and December, 2016. Results: There were 3 891 effective questionnaires. The self-reported prevalence of hypertension among aged ≥35 years was 31.47% (1 011/3 213). For the past two weeks, the self-reported treatment of hypertension was 86.75%(877/1 011), with the rates of guidance as 56.87% (575/1 011) on physical activity, 40.95% (414/1 011) on diet, 38.33% (385/1 011) on weight management, and 22.75% (228/1 011) on smoking cessation. For the past 12 months, 74.68% (755/1 011) of the residents aged ≥35 years were under the proper management and 62.12% (628/1 011) of them were under the standardized management programs. The follow-up program lasted for 4 ( P(25) - P(75) : 4-12) times per year, with 15 ( P(25) - P(75) : 10-20) minutes per each visit. Hypertensive patients would mainly visit the outpatient clinics (53.51%), followed by home visits (22.91%) and telephone calls (13.64%). Rate of satisfaction on management services was 94.83% (716/755) from the hypertensive patients. Multivariate analysis showed that the rate of self-reported treatment ( OR =1.986, 95% CI : 1.222-3.228) and self-reported standardized management ( OR =2.204, 95% CI : 1.519-3.199) on hypertension were higher in the Demonstration Areas with higher implementation scores of self-reported non-communicable diseases management. Conclusions: Prevention and management on hypertension in the Demonstration Areas had met the requirement set for the Demonstration Areas during the "12th Five-Year Plan" . Projects on setting up the National Non-communicable Diseases Demonstration Areas

  2. Tofacitinib 5 mg Twice Daily in Patients with Rheumatoid Arthritis and Inadequate Response to Disease-Modifying Antirheumatic Drugs: A Comprehensive Review of Phase 3 Efficacy and Safety.

    Science.gov (United States)

    Bird, Paul; Bensen, William; El-Zorkany, Bassel; Kaine, Jeffrey; Manapat-Reyes, Bernadette Heizel; Pascual-Ramos, Virginia; Witcombe, David; Soma, Koshika; Zhang, Richard; Thirunavukkarasu, Krishan

    2018-05-24

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We performed a comprehensive review of phase 3 studies of tofacitinib 5 mg twice daily (BID) (approved dose in many countries) in patients with moderate to severe RA and inadequate response to prior disease-modifying antirheumatic drugs. A search of PubMed and ClinicalTrials.gov identified 5 studies: ORAL Solo (NCT00814307), ORAL Sync (NCT00856544), ORAL Standard (included adalimumab 40 mg once every 2 weeks; NCT00853385), ORAL Scan (NCT00847613), and ORAL Step (NCT00960440). Efficacy and safety data for tofacitinib 5 mg BID, placebo, and adalimumab were analyzed. Across the 5 studies, 1216 patients received tofacitinib 5 mg BID, 681 received placebo, and 204 received adalimumab. At month 3, tofacitinib demonstrated significantly higher 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70, respectively) response rates, greater improvement in Health Assessment Questionnaire-Disability Index, and a higher proportion of Disease Activity Score-defined remission than placebo. Frequencies of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar for tofacitinib and placebo at month 3; serious infection events were more frequent for tofacitinib. In ORAL Standard, although not powered for formal comparisons, tofacitinib and adalimumab had numerically similar efficacy and AEs; serious AEs and serious infection events were more frequent with tofacitinib. Tofacitinib 5 mg BID reduced RA signs and symptoms and improved physical function versus placebo in patients with inadequate response to prior disease-modifying antirheumatic drugs. Tofacitinib 5 mg BID had a consistent, manageable safety profile across studies, with no new safety signals identified.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where

  3. 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.

  4. 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)

  5. 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.

  6. 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...

  7. 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...

  8. 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...

  9. 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.

  10. 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.

  11. 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

  12. 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...

  13. 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.

  14. 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.

  15. 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).

  16. 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....

  17. Comprehensive survey of carapacial ridge-specific genes in turtle implies co-option of some regulatory genes in carapace evolution.

    Science.gov (United States)

    Kuraku, Shigehiro; Usuda, Ryo; Kuratani, Shigeru

    2005-01-01

    The turtle shell is an evolutionary novelty in which the developmental pattern of the ribs is radically modified. In contrast to those of other amniotes, turtle ribs grow laterally into the dorsal dermis to form a carapace. The lateral margin of carapacial primordium is called the carapacial ridge (CR), and is thought to play an essential role in carapace patterning. To reveal the developmental mechanisms underlying this structure, we systematically screened for genes expressed specifically in the CR of the Chinese soft-shelled turtle, Pelodiscus sinensis, using microbead-based differential cDNA analysis and real-time reverse transcription-polymerase chain reaction. We identified orthologs of Sp5, cellular retinoic acid-binding protein-I (CRABP-I), adenomatous polyposis coli down-regulated 1 (APCDD1), and lymphoid enhancer-binding factor-1 (LEF-1). Although these genes are conserved throughout the major vertebrate lineages, comparison of their expression patterns with those in chicken and mouse indicated that these genes have acquired de novo expression in the CR in the turtle lineage. In association with the expression of LEF-1, the nuclear localization of beta-catenin protein was detected in the CR ectoderm, suggesting that the canonical Wnt signaling triggers carapace development. These findings indicate that the acquisition of the turtle shell did not involve the creation of novel genes, but was based on the co-option of pre-existing genes.

  18. 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.

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

    Science.gov (United States)

    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. 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)

  1. 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.

  2. 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...

  3. Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: genes and pseudogenes

    Directory of Open Access Journals (Sweden)

    Vasilescu Alexandre

    2005-09-01

    Full Text Available Abstract Background The human genome carries a high load of proviral-like sequences, called Human Endogenous Retroviruses (HERVs, which are the genomic traces of ancient infections by active retroviruses. These elements are in most cases defective, but open reading frames can still be found for the retroviral envelope gene, with sixteen such genes identified so far. Several of them are conserved during primate evolution, having possibly been co-opted by their host for a physiological role. Results To characterize further their status, we presently sequenced 12 of these genes from a panel of 91 Caucasian individuals. Genomic analyses reveal strong sequence conservation (only two non synonymous Single Nucleotide Polymorphisms [SNPs] for the two HERV-W and HERV-FRD envelope genes, i.e. for the two genes specifically expressed in the placenta and possibly involved in syncytiotrophoblast formation. We further show – using an ex vivo fusion assay for each allelic form – that none of these SNPs impairs the fusogenic function. The other envelope proteins disclose variable polymorphisms, with the occurrence of a stop codon and/or frameshift for most – but not all – of them. Moreover, the sequence conservation analysis of the orthologous genes that can be found in primates shows that three env genes have been maintained in a fully coding state throughout evolution including envW and envFRD. Conclusion Altogether, the present study strongly suggests that some but not all envelope encoding sequences are bona fide genes. It also provides new tools to elucidate the possible role of endogenous envelope proteins as susceptibility factors in a number of pathologies where HERVs have been suspected to be involved.

  4. Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases.

    Directory of Open Access Journals (Sweden)

    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 i